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Wang J, Lou W, Li Y, Jiang Y, Jiang X, Yang L. Progress in targeted therapy for ankylosing spondylitis: A review. Medicine (Baltimore) 2024; 103:e40742. [PMID: 39612456 PMCID: PMC11608699 DOI: 10.1097/md.0000000000040742] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/23/2024] [Accepted: 11/08/2024] [Indexed: 12/01/2024] Open
Abstract
Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by axial osteoarticular inflammation and tendon enthesitis with unclear pathogenesis. Nonsteroidal anti-inflammatory drugs and antirheumatic drugs used in the traditional treatment of AS have some problems such as drug intolerance and inadequate treatment response. Since the introduction of biological agents in the treatment of AS, they have completely changed the treatment concept of AS, and because of their safety and good tolerance, they have become the main choice for clinical AS patients. This article systematically summarizes the current status of targeted therapy for AS worldwide, analyzes the advantages and disadvantages of different types of biological agents in the treatment of AS, and provides an objective evaluation of clinical targeted therapy for AS, in order to provide a new perspective for clinical standardized treatment.
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Affiliation(s)
- Jiapeng Wang
- Department of Orthopedics, Jilin Province FAW General Hospital, Changchun City, Jilin Province, China
| | - Wang Lou
- Department of Anesthesiology, Jilin Province FAW General Hospital, Changchun City, Jilin Province, China
| | - Yingnan Li
- Burn the Brotherhood of Plastic Surgery, Jilin Province FAW General Hospital, Changchun City, Jilin Province, China
| | - Yang Jiang
- Department of Medical Laboratory, Jilin Province FAW General Hospital, Changchun City, Jilin Province, China
| | - Xue Jiang
- Department of Rehabilitation, Jilin Province FAW General Hospital, Changchun City, Jilin Province, China
| | - Lin Yang
- Department of Anesthesiology, Jilin Province FAW General Hospital, Changchun City, Jilin Province, China
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Zouris G, Evangelopoulos DS, Benetos IS, Vlamis J. The Use of TNF-α Inhibitors in Active Ankylosing Spondylitis Treatment. Cureus 2024; 16:e61500. [PMID: 38952586 PMCID: PMC11216526 DOI: 10.7759/cureus.61500] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/01/2024] [Indexed: 07/03/2024] Open
Abstract
Ankylosing spondylitis (AS) is a challenging disease, characterized by chronic inflammation and structural damage primarily affecting the axial skeleton, while extra-articular manifestations may also appear. This results in the deterioration of patients' quality of life. Over the past few decades, tumor necrosis factor-α (TNF-α) inhibitors have revolutionized the management of AS, offering substantial relief from symptoms and improving patient outcomes. The aim of this review is to assess the efficacy of TNF-α inhibitors in patients with active AS. A search was performed in the PubMed database using the following keywords: ("TNF alpha inhibitors" OR "anti TNF-a" OR "TNF-a inhibitors" OR "anti TNF-alpha" OR "Etanercept " OR "Golimumab" OR "Infliximab" OR "Certolizumab pegol" OR "Adalimumab") AND "ankylosing spondylitis". The search was completed in February 2024, and 35 studies were included in this review following PRISMA guidelines. The findings reveal evidence supporting the efficacy of TNF-α inhibitors in reducing inflammation, preventing structural damage, and enhancing overall well-being in AS patients. Overall, TNF-α inhibitors have emerged as a cornerstone in the therapeutic algorithm against AS with a very satisfactory safety profile.
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Affiliation(s)
- Georgios Zouris
- 5th Orthopaedic Department, General Hospital "Asklepieio" Voulas, Athens, GRC
- Postgraduate Training Program, KAT Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, GRC
| | - Dimitrios Stergios Evangelopoulos
- 3rd Orthopaedic Department, KAT Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, GRC
- Postgraduate Training Program, KAT Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, GRC
- Metabolic Bone Diseases Department, KAT Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, GRC
| | - Ioannis S Benetos
- 3rd Orthopaedic Department, KAT Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, GRC
- Postgraduate Training Program, KAT Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, GRC
| | - John Vlamis
- 3rd Orthopaedic Department, KAT Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, GRC
- Postgraduate Training Program, KAT Hospital, National and Kapodistrian University of Athens School of Medicine, Athens, GRC
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Wang CR, Tsai HW. Seronegative spondyloarthropathy-associated inflammatory bowel disease. World J Gastroenterol 2023; 29:450-468. [PMID: 36688014 PMCID: PMC9850936 DOI: 10.3748/wjg.v29.i3.450] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/30/2022] [Revised: 11/18/2022] [Accepted: 12/21/2022] [Indexed: 01/12/2023] Open
Abstract
Seronegative spondyloarthropathy (SpA) usually starts in the third decade of life with negative rheumatoid factor, human leukocyte antigen-B27 genetic marker and clinical features of spinal and peripheral arthritis, dactylitis, enthesitis and extra-articular manifestations (EAMs). Cases can be classified as ankylosing spondylitis, psoriatic arthritis, reactive arthritis, enteropathic arthritis, or juvenile-onset spondyloarthritis. Joint and gut inflammation is intricately linked in SpA and inflammatory bowel disease (IBD), with shared genetic and immunopathogenic mechanisms. IBD is a common EAM in SpA patients, while extraintestinal manifestations in IBD patients mostly affect the joints. Although individual protocols are available for the management of each disease, the standard therapeutic guidelines of SpA-associated IBD patients remain to be established. Nonsteroidal anti-inflammatory drugs are recommended as initial therapy of peripheral and axial SpA, whereas their use is controversial in IBD due to associated disease flares. Conventional disease-modifying anti-rheumatic drugs are beneficial for peripheral arthritis but ineffective for axial SpA or IBD therapy. Anti-tumor necrosis factor monoclonal antibodies are effective medications with indicated use in SpA and IBD, and a drug of choice for treating SpA-associated IBD. Janus kinase inhibitors, approved for treating SpA and ulcerative colitis, are promising therapeutics in SpA coexistent with ulcerative colitis. A tight collaboration between gastroenterologists and rheumatologists with mutual referral from early accurate diagnosis to appropriately prompt therapy is required in this complex clinical scenario.
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Affiliation(s)
- Chrong-Reen Wang
- Department of Internal Medicine, National Cheng Kung University Hospital, Tainan 70403, Taiwan
| | - Hung-Wen Tsai
- Department of Pathology, National Cheng Kung University Hospital, Tainan 70403, Taiwan
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Spondyloarthropathy in Inflammatory Bowel Disease: From Pathophysiology to Pharmacological Targets. Drugs 2022; 82:1151-1163. [PMID: 35900700 DOI: 10.1007/s40265-022-01750-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/03/2022] [Indexed: 11/03/2022]
Abstract
Spondyloarthritis (SpA) represents one of the most frequent extraintestinal manifestations of inflammatory bowel disease (IBD). Evidence of shared genetic and molecular pathways underlying both diseases is emerging, which has led to rational approaches when treating patients with concomitant diseases. Clinical efficacy of tumor necrosis factor (TNF) antagonists has been ascertained over the years, and they currently represent the cornerstone of treatment in patients with IBD and SpA, but the therapeutic armamentarium in these cases has been recently expanded. Evidence for vedolizumab is controversial, as it was associated both with improvement and development of arthralgias, while ustekinumab, the first anti-interleukin 12/23 (IL-12/23) approved for IBD, has demonstrated good efficacy, especially in peripheral arthritis, and more IL-23 inhibitors are being developed in IBD. Tofacitinib was the first Janus kinase (JAK) inhibitor to be approved in IBD, and as it demonstrated efficacy in treating ankylosing spondylitis, it may represent a good choice in axial arthritis, while more selective JAK inhibitors are yet to be approved. Unexpectedly, the first anti-IL17 that was studied in IBD (secukinumab) has shown not to be effective in treating IBD, and the role of anti-IL17 drugs in these diseases needs further investigation. Therefore, as availability of biologics and small molecules is increasing, their positioning in clinical practice is becoming more and more challenging, and multidisciplinary management needs to be implemented in both research and clinical settings in order to enhance early recognition of SpA in IBD patients, optimize treatment and ultimately improve the patients' quality of life.
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Braun J, Kiltz U, Deodhar A, Tomita T, Dougados M, Bolce R, Sandoval D, Lin CY, Walsh J. Efficacy and safety of ixekizumab treatment in patients with axial spondyloarthritis: 2-year results from COAST. RMD Open 2022; 8:rmdopen-2021-002165. [PMID: 35853675 PMCID: PMC9301795 DOI: 10.1136/rmdopen-2021-002165] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2021] [Accepted: 05/23/2022] [Indexed: 11/04/2022] Open
Abstract
OBJECTIVES To study the efficacy and safety of ixekizumab (IXE) in patients with radiographic (r-) and non-radiographic (nr-)axial spondyloarthritis (axSpA) for up to 116 weeks. METHODS COAST-Y (NCT03129100) is the 2-year extension study following COAST-V, COAST-W and COAST-X. Patients were treated with either 80 mg IXE every 4 weeks or 2 weeks, as assigned in the originating studies. Efficacy was assessed in all participants continuously treated with IXE through week 116 and in subgroups based on disease subtype and dosing. Missing data were handled by non-responder imputation for categorical variables and modified baseline observation carried forward for continuous variables. Safety data were analysed in all patients having received ≥1 IXE dose. RESULTS Of 932 patients who received ≥1 IXE dose, 773 enrolled in COAST-Y (82.9%); 665 of which (86.0%) completed week 116. Of 352 continuously treated patients, the proportion achieving Assessment of Spondyloarthritis International Society (ASAS40) at week 52 was 51.4%, which increased to 56.0% at week 116. The proportion of patients achieving ASAS40 at week 116 was 64.9% and 57.7% for biological disease-modifying antirheumatic drug (bDMARD)-naïve patients with r-axSpA and nr-axSpA, respectively, and 47.0% for TNFi-experienced patients. The proportion of patients achieving Ankylosing Spondylitis Disease Activity Score <2.1 through week 116 was 57.0% and 52.9% for bDMARD-naïve patients with r-axSpA and nr-axSpA, respectively, and 33.6% for TNFi-experienced patients. Incidences of treatment-emergent adverse events and serious adverse events were consistent with previous reports. CONCLUSION IXE treatment led to sustained long-term improvements in patients with axSpA, with similar efficacy for r-axSpA and nr-axSpA, and for patients receiving the approved every 4 weeks dose. The safety profile of IXE was consistent with previous reports. No new safety signals were identified.
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Affiliation(s)
- Jürgen Braun
- Rheumazentrum Ruhrgebiet, Herne, and Department of Biochemistry, Ruhr Universität, Bochum, Germany
| | - Uta Kiltz
- Rheumazentrum Ruhrgebiet, Herne, and Department of Biochemistry, Ruhr Universität, Bochum, Germany
| | - Atul Deodhar
- Division of Arthritis and Rheumatic Diseases, School of Medicine, Oregon Health & Science University, Portland, Oregon, USA
| | - Tetsuya Tomita
- Department of Orthopaedic Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| | | | | | | | - Chen-Yen Lin
- Eli Lilly and Company, Indianapolis, Indiana, USA
| | - Jessica Walsh
- Division of Rheumatology, University of Utah, Salt Lake City, Utah, USA
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Kamoi K, Watanabe T, Uchimaru K, Okayama A, Kato S, Kawamata T, Kurozumi-Karube H, Horiguchi N, Zong Y, Yamano Y, Hamaguchi I, Nannya Y, Tojo A, Ohno-Matsui K. Updates on HTLV-1 Uveitis. Viruses 2022; 14:v14040794. [PMID: 35458524 PMCID: PMC9030471 DOI: 10.3390/v14040794] [Citation(s) in RCA: 16] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/26/2022] [Revised: 04/07/2022] [Accepted: 04/08/2022] [Indexed: 02/06/2023] Open
Abstract
HTLV-1 uveitis (HU) is the third clinical entity to be designated as an HTLV-1-associated disease. Although HU is considered to be the second-most frequent HTLV-1-associated disease in Japan, information on HU is limited compared to that on adult T-cell leukemia/lymphoma (ATL) and HTLV-1-associated myelopathy (HAM). Recent studies have addressed several long-standing uncertainties about HU. HTLV-1-related diseases are known to be caused mainly through vertical transmission (mother-to-child transmission), but emerging HTLV-1 infection by horizontal transmission (such as sexual transmission) has become a major problem in metropolitan areas, such as Tokyo, Japan. Investigation in Tokyo showed that horizontal transmission of HTLV-1 was responsible for HU with severe and persistent ocular inflammation. The development of ATL and HAM is known to be related to a high provirus load and hence involves a long latency period. On the other hand, factors contributing to the development of HU are poorly understood. Recent investigations revealed that severe HU occurs against a background of Graves’ disease despite a low provirus load and short latency period. This review highlights the recent knowledge on HU and provides an update on the topic of HU in consideration of a recent nationwide survey.
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Affiliation(s)
- Koju Kamoi
- Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan; (H.K.-K.); (N.H.); (Y.Z.); (K.O.-M.)
- Department of Hematology/Oncology, Research Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; (T.W.); (K.U.); (S.K.); (T.K.); (Y.N.); (A.T.)
- Correspondence: ; Tel.: +81-3-5803-5302
| | - Toshiki Watanabe
- Department of Hematology/Oncology, Research Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; (T.W.); (K.U.); (S.K.); (T.K.); (Y.N.); (A.T.)
- Department of Practical Management of Medical Information, St. Marianna University School of Medicine, Kanagawa 216-8512, Japan
| | - Kaoru Uchimaru
- Department of Hematology/Oncology, Research Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; (T.W.); (K.U.); (S.K.); (T.K.); (Y.N.); (A.T.)
- Department of Medical Computational Biology and Genome Sciences, Laboratory of Tumor Cell Biology, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo 108-8639, Japan
| | - Akihiko Okayama
- Department of Rheumatology, Infectious Diseases and Laboratory Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki 889-1601, Japan;
| | - Seiko Kato
- Department of Hematology/Oncology, Research Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; (T.W.); (K.U.); (S.K.); (T.K.); (Y.N.); (A.T.)
| | - Toyotaka Kawamata
- Department of Hematology/Oncology, Research Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; (T.W.); (K.U.); (S.K.); (T.K.); (Y.N.); (A.T.)
| | - Hisako Kurozumi-Karube
- Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan; (H.K.-K.); (N.H.); (Y.Z.); (K.O.-M.)
| | - Noe Horiguchi
- Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan; (H.K.-K.); (N.H.); (Y.Z.); (K.O.-M.)
| | - Yuan Zong
- Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan; (H.K.-K.); (N.H.); (Y.Z.); (K.O.-M.)
| | - Yoshihisa Yamano
- Division of Neurology, Department of Internal Medicine, St. Marianna University School of Medicine, Kanagawa 216-8511, Japan;
| | - Isao Hamaguchi
- Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, Tokyo 208-0011, Japan;
| | - Yasuhito Nannya
- Department of Hematology/Oncology, Research Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; (T.W.); (K.U.); (S.K.); (T.K.); (Y.N.); (A.T.)
| | - Arinobu Tojo
- Department of Hematology/Oncology, Research Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo 108-8639, Japan; (T.W.); (K.U.); (S.K.); (T.K.); (Y.N.); (A.T.)
- Institute of Innovation Advancement, Tokyo Medical and Dental University, Tokyo 113-8510, Japan
| | - Kyoko Ohno-Matsui
- Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, Tokyo 113-8510, Japan; (H.K.-K.); (N.H.); (Y.Z.); (K.O.-M.)
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Garcia-Montoya L, Emery P. Disease modification in ankylosing spondylitis with TNF inhibitors: spotlight on early phase clinical trials. Expert Opin Investig Drugs 2021; 30:1109-1124. [PMID: 34842481 DOI: 10.1080/13543784.2021.2010187] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
INTRODUCTION Ankylosing spondylitis (AS) is a chronic inflammatory disease whose main hallmark is involvement of the axial skeleton. Non-steroidal anti-inflammatory drugs (NSAIDs) are the first line treatment; however, their use is limited because of side effects. Tumor necrosis factor inhibitors (TNFi) are a safe and effective therapy, and they have been approved for the management of AS. AREAS COVERED This is a review of the efficacy of TNFi in disease modification in AS. It is focused on results from early-phase clinical trials; however, it also discusses the most relevant findings in order to optimize anti-TNF treatment. A literature search was done using PubMed, Medline, Embase, Google Scholar, and Cochrane library, looking for scientific publications from inception to August 2021. Further information was retrieved from ClinicalTrial.gov and Clinicaltrialsregister.eu. EXPERT OPINION TNFi have demonstrated short- and long-term improvements in all aspects of disease activity, as well as physical function in patients with AS. They have drastically revolutionized the management of the disease; and even though new drugs have become available in the market, TNFi has not been displaced for the treatment of AS, and still constitute the best alternative when NSAIDs are no-longer an option.
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Affiliation(s)
- Leticia Garcia-Montoya
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.,National Institute for Health Research, Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | - Paul Emery
- Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK.,National Institute for Health Research, Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK
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Tatsuoka J, Igarashi T, Kajimoto R, Kobayashi M, Moro N, Suma T, Oshima H, Yoshino A. High-dose-infliximab-associated Cerebral Venous Sinus Thrombosis: A Case Report and Review of the Literature. Intern Med 2021; 60:2677-2681. [PMID: 33678739 PMCID: PMC8429287 DOI: 10.2169/internalmedicine.6447-20] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/26/2022] Open
Abstract
A 28-year-old woman experienced severe headache and right homonymous hemianopia after receiving high-dose infliximab for Crohn's disease. Computed tomography showed hemorrhagic infarction in the left temporal and parietal lobes. An angiogram revealed left transverse to sigmoid sinus occlusion and a stagnated Labbe vein. The patient was treated surgically and achieved a good outcome. Inflammatory bowel diseases are known to accompany venous and arterial thrombosis in 1-2% of cases. Recently, infliximab has been suggested to increase this possibility. A case of Crohn's disease presenting with cerebral sinus thrombosis in the remission period during long-term/high-dose use of infliximab is presented. In addition, infliximab-associated thrombosis cases were reviewed.
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Affiliation(s)
- Juri Tatsuoka
- Division of Neurosurgery, Department of Neurological Surgery, Nihon University School of Medicine, Japan
| | - Takahiro Igarashi
- Division of Neurosurgery, Department of Neurological Surgery, Nihon University School of Medicine, Japan
| | - Ryuta Kajimoto
- Division of Neurosurgery, Department of Neurological Surgery, Nihon University School of Medicine, Japan
| | - Masato Kobayashi
- Division of Neurosurgery, Department of Neurological Surgery, Nihon University School of Medicine, Japan
| | - Nobuhiro Moro
- Division of Neurosurgery, Department of Neurological Surgery, Nihon University School of Medicine, Japan
| | - Takeshi Suma
- Division of Neurosurgery, Department of Neurological Surgery, Nihon University School of Medicine, Japan
| | - Hideki Oshima
- Division of Neurosurgery, Department of Neurological Surgery, Nihon University School of Medicine, Japan
| | - Atsuo Yoshino
- Division of Neurosurgery, Department of Neurological Surgery, Nihon University School of Medicine, Japan
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McGonagle D, Aydin SZ, Marzo-Ortega H, Eder L, Ciurtin C. Hidden in plain sight: Is there a crucial role for enthesitis assessment in the treatment and monitoring of axial spondyloarthritis? Semin Arthritis Rheum 2021; 51:1147-1161. [PMID: 34537464 DOI: 10.1016/j.semarthrit.2021.07.011] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2021] [Accepted: 07/05/2021] [Indexed: 01/06/2023]
Abstract
OBJECTIVE To review the evidence surrounding the pathophysiology of enthesitis in axial spondyloarthritis (axSpA), its prevalence and contribution to the overall disease burden, and response to treatment at axial and peripheral sites. METHODS Literature searches of the Cochrane Library, PubMed, and Embase / Medline using the terms "enthesitis", "enthesopathy", "spondyloarthritis", "axial spondyloarthritis", and "ankylosing spondylitis" were conducted. Publications mentioning enthesitis or enthesopathy in the context of pathophysiology, diagnosis, or treatment were included. RESULTS Enthesitis is a common symptom of axSpA, occurring with high prevalence at axial and several peripheral sites. Inflammation at the site of enthesis is an early key manifestation of axSpA. Clinically evaluable enthesitis contributes significantly to the burden of disease, correlating with worse symptomatology and downstream structural damage. Despite its importance in driving axSpA disease processes, enthesitis is somewhat neglected in current approaches to disease assessment and management. Enthesitis is excluded from some commonly used disease activity measures, is not routinely assessed in clinical practice, and many methods of clinical assessment omit key accessible axial sites, such as the spinous processes. CONCLUSION Enthesitis plays a central role in driving the pathophysiology of axSpA. There is a need for a renewed focus on the early detection, measurement and treatment of enthesitis.
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Affiliation(s)
- Dennis McGonagle
- The Leeds Institute of the Rheumatic and Musculoskeletal Disease, University of Leeds, Chapeltown Road, Leeds LS7 4SA, United Kingdom; National Institute for Health Research, Leeds Biomedical Research Centre, Leeds Teaching Hospitals Trust, Leeds, United Kingdom.
| | - Sibel Z Aydin
- Division of Rheumatology, Department of Internal Medicine, Faculty of Medicine, University of Ottawa, and Ottawa Hospital Research Institute, Ottawa, Canada
| | - Helena Marzo-Ortega
- The Leeds Institute of the Rheumatic and Musculoskeletal Disease, University of Leeds, Chapeltown Road, Leeds LS7 4SA, United Kingdom; National Institute for Health Research, Leeds Biomedical Research Centre, Leeds Teaching Hospitals Trust, Leeds, United Kingdom
| | - Lihi Eder
- Division of Rheumatology, Department of Medicine, Women's College Research Institute, Women's College Hospital, University of Toronto, Canada
| | - Coziana Ciurtin
- Department of Rheumatology, Centre for Adolescent Rheumatology Versus Arthritis, Department of Medicine, University College London, Rayne Building, London, United Kingdom
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10
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Su J, Li M, He L, Zhao D, Wan W, Liu Y, Xu J, Xu J, Liu H, Jiang L, Wu H, Zuo X, Huang C, Liu X, Li F, Zhang Z, Liu X, Dong L, Li T, Chen H, Li J, He D, Lu X, Huang A, Tao Y, Wang Y, Zhang Z, Wei W, Li X, Zeng X. Changes in Efficacy Indicators for Adalimumab Biosimilar Candidate (HS016) for the Treatment of Active Ankylosing Spondylitis at Various Time Points. Front Pharmacol 2020; 11:606497. [PMID: 33364967 PMCID: PMC7750525 DOI: 10.3389/fphar.2020.606497] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/15/2020] [Accepted: 11/12/2020] [Indexed: 02/05/2023] Open
Abstract
Objectives: A phase III, 24-weeks Chinese clinical trial demonstrated that efficacy and safety outcomes of treatments with 40 mg/0.8 ml HS016 (n = 416) or adalimumab (n = 232) for active ankylosing spondylitis (AS) patients was comparable. In the present study, a subanalysis of the clinical trial was conducted to determine whether also individual efficacy indicators were comparable between HS016 and adalimumab. Methods: The individual efficacy indicators total and nocturnal back pain, global assessment of disease activity, swollen joint count, Maastricht AS Enthesitis Score, Bath AS Disease Activity Index, Bath AS Functional Index, Bath AS Metrology Index and chest expansion, were assessed at baseline and every 2 weeks during the treatment period. Results: This subanalysis revealed no significant difference between the patient groups treated with HS016 or adalimumab for any individual efficacy indicator investigated at any time point (all p > 0.05) beside faster total back pain score improvements in the adalimumab group on week 10, 12 and 22, which became equal at week 24. Among these indicators, chest expansion showed a significant increase at each time point compared with baseline, whereas all other efficacy indicators showed significant decreases compared with baseline at each time point (all p < 0.05). All efficacy indicators had increased or decreased rapidly by week 2, and the values continued to increase/decrease up to week 12, with subsequent smaller changes thereafter up to week 24 of treatment. Conclusion: The response trajectory of most individual efficacy indicators was comparable between HS016 and adalimumab at each time point during the 24 weeks of the trial. Clinical Trial Registration: http://www.chictr.org.cn/showproj.aspx?proj=37910, identifier [ChiCTR1900022520].
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Affiliation(s)
- Jinmei Su
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, National Clinical Research Center for Immunologic Diseases, Ministry of Science and Technology, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Mengtao Li
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, National Clinical Research Center for Immunologic Diseases, Ministry of Science and Technology, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
| | - Lan He
- Department of Rheumatology and Immunology, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, China
| | - Dongbao Zhao
- Department of Rheumatology, Changhai Hospital, Shanghai, China
| | - Weiguo Wan
- Department of Rheumatology, Huashan Hospital, Fudan University, Shanghai, China
| | - Yi Liu
- Department of Rheumatology, West China Hospital, Sichuan University, Chengdu, China
| | - Jianhua Xu
- Department of Rheumatology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
| | - Jian Xu
- Department of Rheumatology, The First Affiliated Hospital of Kunming Medical University, Kunming, China
| | - Huaxiang Liu
- Department of Rheumatology, Qilu Hospital of Shandong University, Jinan, China
| | - Lindi Jiang
- Department of Rheumatology, Zhongshan Hospital, Fudan University, Shanghai, China
| | - Huaxiang Wu
- Department of Rheumatology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, China
| | - Xiaoxia Zuo
- Department of Rheumatology, Xiangya Hospital, Central South University, Changsha, China
| | - Cibo Huang
- Department of Rheumatology, Beijing Hospital, Beijing, China
| | - Xiumei Liu
- Department of Rheumatology, The First Affiliated Hospital of Shanxi Medical University, Taiyuan, China
| | - Fen Li
- Department of Rheumatology, The Second Xiangya Hospital of Central South University, Changsha, China
| | - Zhiyi Zhang
- Department of Rheumatology, The First Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Xiangyuan Liu
- Department of Rheumatology, Peking University Third Hospital, Beijing, China
| | - Lingli Dong
- Department of Rheumatology, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
| | - Tianwang Li
- Department of Rheumatology, Guangdong Second Provincial General Hospital, Guangzhou, China
| | - Haiying Chen
- Department of Rheumatology, The Third Hospital of Hebei Medical University, Shijiazhuang, China
| | - Jingyang Li
- Department of Rheumatology, Zhuzhou Central Hospital, Zhuzhou, China
| | - Dongyi He
- Department of Rheumatology, Shanghai Guanghua Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai, China
| | - Xin Lu
- Department of Rheumatology, China-Japan Friendship Hospital, Beijing, China
| | - Anbin Huang
- Department of Rheumatology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China
| | - Yi Tao
- Department of Rheumatology, The Second Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Yanyan Wang
- Department of Rheumatology, Jiangsu Province Hospital, Nanjing, China
| | - Zhuoli Zhang
- Department of Rheumatology, Peking University First Hospital, Beijing, China
| | - Wei Wei
- Department of Rheumatology, Tianjin Medical University General Hospital, Tianjin, China
| | - Xiaofeng Li
- Department of Rheumatology, The Second Affiliated Hospital of Shanxi Medical University, Taiyuan, China
| | - Xiaofeng Zeng
- Department of Rheumatology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, National Clinical Research Center for Immunologic Diseases, Ministry of Science and Technology, Key Laboratory of Rheumatology and Clinical Immunology, Ministry of Education, Beijing, China
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11
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Kurozumi-Karube H, Kamoi K, Ando N, Uchida M, Hamaguchi I, Ohno-Matsui K. In vitro Evaluation of the Safety of Adalimumab for the Eye Under HTLV-1 Infection Status: A Preliminary Study. Front Microbiol 2020; 11:522579. [PMID: 33424777 PMCID: PMC7785715 DOI: 10.3389/fmicb.2020.522579] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/23/2019] [Accepted: 12/07/2020] [Indexed: 01/29/2023] Open
Abstract
Adalimumab (ADA), a fully human monoclonal tumor necrosis factor (TNF)-α antibody, is one of the most widely used biologics in the treatment of inflammatory diseases. However, ADA can exacerbate infectious conditions, induce paradoxical reactions such as inflammation, and cause neoplasia. Human T-cell leukemia virus type 1 (HTLV-1) is an infectious agent that induces inflammation and neoplastic infiltration in the eye. To date, numerous HTLV-1 carriers have been treated with adalimumab to suppress inflammation out of necessity, when standard anti-inflammatory drugs such as steroids and immunosuppressive agents have proven inadequate to control the inflammation. Here, we clarify the safety of adalimumab for the eye under HTLV-1 infectious conditions in vitro. We used the adult retinal pigment epithelial cell line (ARPE)-19 cell line as ocular resident cells, and used MT2 and TL-Om1 as HTLV-1-infected cells. ARPE-19 and MT2/TL-Om1 were co-cultured, and then adalimumab was administered. Production of cytokines and chemokines, TNF-α receptor (TNF-R), HTLV-1 proviral load (PVL), and apoptosis were measured to assess the effects of adalimumab. Contact between ARPE-19 and MT2/TL-Om1 produced inflammatory cytokines such as TNF, interleukin (IL)-6, IL-8 and IL-10, and transduced chemokines such as interferon-inducible protein-10 (IP-10), monocyte chemotactic protein-1 (MCP-1), monokine induced by interferon-γ (MIG), and regulated on activation, normal T cell expressed and secreted (RANTES). No inflammatory cytokines and chemokines were exacerbated by adalimumab. Expression of TNF-R on ARPE-19 and MT2/TL-Om1 cells, HTLV-1 PVLs of MT2/TL-Om1 cells, and cell growth rate and apoptotic rate of ARPE-19 were unaffected by adalimumab. In conclusion, adalimumab does not appear to exacerbate HTLV-1-associated inflammatory conditions in the eye or increase PVL in HTLV-1-infected T cells. These data suggest that adalimumab could be used safely for the eye under HTLV-1 infectious conditions from the perspective of in vitro assessment.
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Affiliation(s)
- Hisako Kurozumi-Karube
- Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan
| | - Koju Kamoi
- Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan
| | - Naoko Ando
- Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan
| | - Minami Uchida
- Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan
| | - Isao Hamaguchi
- Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, Tokyo, Japan
| | - Kyoko Ohno-Matsui
- Department of Ophthalmology & Visual Science, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan
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12
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Achievement of Remission Endpoints with Secukinumab Over 3 Years in Active Ankylosing Spondylitis: Pooled Analysis of Two Phase 3 Studies. Rheumatol Ther 2020; 8:273-288. [PMID: 33351179 PMCID: PMC7991028 DOI: 10.1007/s40744-020-00269-6] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Accepted: 12/05/2020] [Indexed: 12/28/2022] Open
Abstract
Introduction Clinical remission in patients with ankylosing spondylitis (AS) has been determined using composite indices such as the AS Disease Activity Score inactive disease (ASDAS-ID), Assessment of SpondyloArthritis international Society criteria partial remission (ASAS-PR), and low Bath AS Disease Activity Index (BASDAI) scores. The objective of this exploratory analysis was to evaluate the proportion of secukinumab-treated patients with AS achieving remission defined based on the ASDAS-ID (score < 1.3), ASAS-PR or BASDAI score ≤ 2. Methods The analysis pooled data from the MEASURE 1 and 2 studies over 3 years. The proportion of patients who achieved ASDAS-ID, ASAS-PR, or BASDAI ≤ 2 with secukinumab was compared with placebo at week 16; results for secukinumab-treated patients were summarized through week 156. Sustainability of each criterion was assessed from week 16 to 156 using shift analysis. The association between each of these criteria and specific patient-reported outcomes (PROs), such as health-related quality of life, function, fatigue, and work impairment, was also explored. Results At week 16, a higher proportion of secukinumab-treated patients versus placebo achieved ASDAS-ID (17.6 vs. 3.5%), ASAS-PR (15.4 vs. 4.1%), or BASDAI ≤ 2 (22.3 vs. 6.4%) criteria (all P < 0.0001), which were sustained through 156 weeks. Shift analysis showed that the majority of secukinumab-treated patients achieving remission at week 16 maintained their status at week 156 (ASDAS-ID, 57.1%; ASAS-PR, 68.0% and BASDAI ≤ 2, 74.3%). Remission was also associated with improved PROs over 156 weeks. Conclusions Secukinumab-treated patients maintained ASDAS-ID, ASAS-PR, or BASDAI ≤ 2 from week 16 up to 3 years. Patients who achieved at least one of the three responses/states, reported improvement in PROs, which suggests an association of clinical remission/ID with PROs in patients with active AS. Trial registration ClinicalTrials.gov: NCT01358175, NCT01863732, and NCT01649375 Supplementary Information The online version contains supplementary material available at 10.1007/s40744-020-00269-6.
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13
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Cruz-Machado AR, Rodrigues-Manica S, Silva JL, Alho I, Coelho C, Duarte J, Florêncio C, Pimentel-Santos FM, Tavares-Costa J, Vieira-Sousa E. Effect of biologic disease-modifying anti-rheumatic drugs targeting remission in axial spondyloarthritis: systematic review and meta-analysis. Rheumatology (Oxford) 2020; 59:3158-3171. [PMID: 32696064 DOI: 10.1093/rheumatology/keaa268] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2019] [Revised: 03/17/2020] [Accepted: 04/08/2020] [Indexed: 01/20/2023] Open
Abstract
OBJECTIVES To assess the efficacy of biologic DMARDs (bDMARDs) in achieving Assessment of Spondyloarthritis International Society partial remission (ASAS-PR) and/or Ankylosing Spondylitis Disease Activity Score inactive disease (ASDAS-ID), as remission-like surrogates, in axial SpA (axSpA). METHODS Data from randomized controlled trials (RCTs), including long-term extensions, were included. A systematic literature review was performed using the MEDLINE database (first search May 2018, updated February 2020) and PICO criteria according to Patients-adults with radiographic or non-radiographic axSpA; Intervention-any bDMARD; Comparator-placebo and/or any different drug; Outcomes-ASAS-PR and/or ASDAS-ID as primary or secondary endpoints. Meta-analysis was performed after assessment of the homogeneity of study designs, populations and outcomes. RESULTS After screening 155 references, a total of 22 RCTs and 28 long-term extensions were retrieved. ASAS-PR was the dominant remission-like definition used. Concerning TNF inhibitors, 14/17 RCTs provided evidence of efficacy in reaching remission at different time points: 12, 16, 24 and 28 weeks (ASAS-PR in 16-62% of patients and ASDAS-ID in 24-40% of patients). With a limited number of studies available, IL-17A inhibitors exhibited remission rates of 15-21% for ASAS-PR and 11-16% for ASDAS-ID at week 16. A meta-analysis regarding ASAS-PR was performed considering RCTs with a similar duration (12, 16 or 24 weeks). The relative risk for achieving remission was 3.864 (95% CI 2.937, 5.085). CONCLUSION bDMARDs have a clear impact in axSpA remission evaluated by ASAS-PR. Nevertheless, these data show an unmet need for improved reporting of remission-like outcomes.
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Affiliation(s)
- Ana Rita Cruz-Machado
- Rheumatology Department, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Lisbon Academic Medical Centre, Lisbon, Portugal.,Rheumatology Research Unit, Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
| | - Santiago Rodrigues-Manica
- Rheumatology Department, Hospital Egas Moniz, Centro Hospitalar de Lisboa Ocidental, Lisbon, Portugal.,CEDOC, NOVA Medical School, Lisbon, Portugal
| | - Joana Leite Silva
- Rheumatology Department, Unidade Local de Saúde do Alto Minho, Ponte de Lima, Portugal
| | - Irina Alho
- Genetics Laboratory, Institute of Environmental Health, Lisbon Medical School, University of Lisbon, Lisbon, Portugal
| | - Constança Coelho
- Genetics Laboratory, Institute of Environmental Health, Lisbon Medical School, University of Lisbon, Lisbon, Portugal
| | - Joana Duarte
- Medical Department, Novartis Pharma, Porto Salvo, Portugal
| | | | - Fernando M Pimentel-Santos
- Rheumatology Department, Hospital Egas Moniz, Centro Hospitalar de Lisboa Ocidental, Lisbon, Portugal.,CEDOC, NOVA Medical School, Lisbon, Portugal
| | - José Tavares-Costa
- Rheumatology Department, Unidade Local de Saúde do Alto Minho, Ponte de Lima, Portugal
| | - Elsa Vieira-Sousa
- Rheumatology Department, Hospital de Santa Maria, Centro Hospitalar Universitário Lisboa Norte, Lisbon Academic Medical Centre, Lisbon, Portugal.,Rheumatology Research Unit, Instituto de Medicina Molecular João Lobo Antunes, Faculdade de Medicina, Universidade de Lisboa, Lisbon, Portugal
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14
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Shim J, Dean LE, Karabayas M, Jones GT, Macfarlane GJ, Basu N. Quantifying and predicting the effect of anti-TNF therapy on axSpA-related fatigue: results from the BSRBR-AS registry and meta-analysis. Rheumatology (Oxford) 2020; 59:3408-3414. [PMID: 32337555 PMCID: PMC7590410 DOI: 10.1093/rheumatology/keaa132] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/02/2019] [Revised: 02/24/2020] [Indexed: 01/20/2023] Open
Abstract
OBJECTIVES Effective management of axial spondyloarthritis (axSpA)-related fatigue is a major unmet clinical need. Anti-TNF therapy may reduce fatigue levels, although any effect has yet to be definitively quantified and predictors of any such improvements are unknown. METHODS The British Society of Rheumatology Register in Axial Spondyloarthritis (BSRBR-AS) prospectively recruited axSpA patients across the UK. Changes in fatigue levels (measured using the Chalder Fatigue Scale) >1 year were compared between those starting anti-TNF therapy at the time of recruitment and those not. Differences between treatment groups were adjusted using propensity score matching. Results were meta-analysed with the extant literature to calculate pooled estimates. Then, among those BSRBR-AS anti-TNF commencers with clinically relevant fatigue, baseline predictors of response were investigated. RESULTS Of the 998 BSRBR-AS recruits with complete fatigue data, 310 were anti-TNF commencers. At 1-year follow-up, the former group reported a mean fatigue change of -2.6 (95% CI -4.1, -1.9) points while the latter reported a mean worsening of fatigue by 0.2 points. Following propensity score adjustment, those commencing anti-TNF therapy reduced fatigue by 3.0 points compared with those not. Of those with significant fatigue and commencing anti-TNF, poor sleep quality at baseline predicted fatigue improvement. In the meta-analysis, including 1109 subjects, treatment with anti-TNF therapy resulted in a significant improvement in fatigue [Standardized mean difference (SMD) = 0.36, 95% CI 0.15, 1.56]. CONCLUSION Anti-TNF therapy results in a significant but modest reduction in fatigue amongst axSpA patients, with those reporting poor sleep quality most likely to report improvement. Effective management will likely require additional approaches.
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Affiliation(s)
- Joanna Shim
- Epidemiology Group, School of Medicine, Medical Sciences and Nutrition.,Aberdeen Centre for Arthritis and Musculoskeletal Health.,Medical Research Council/Versus Arthrtis Centre for Musculoskeletal Health and Work, University of Aberdeen.,Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK
| | - Linda E Dean
- Epidemiology Group, School of Medicine, Medical Sciences and Nutrition.,Aberdeen Centre for Arthritis and Musculoskeletal Health.,Medical Research Council/Versus Arthrtis Centre for Musculoskeletal Health and Work, University of Aberdeen
| | - Maira Karabayas
- Department of Rheumatology, Aberdeen Royal Infirmary, Aberdeen
| | - Gareth T Jones
- Epidemiology Group, School of Medicine, Medical Sciences and Nutrition.,Aberdeen Centre for Arthritis and Musculoskeletal Health.,Medical Research Council/Versus Arthrtis Centre for Musculoskeletal Health and Work, University of Aberdeen
| | - Gary J Macfarlane
- Epidemiology Group, School of Medicine, Medical Sciences and Nutrition.,Aberdeen Centre for Arthritis and Musculoskeletal Health.,Medical Research Council/Versus Arthrtis Centre for Musculoskeletal Health and Work, University of Aberdeen
| | - Neil Basu
- Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK
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15
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Resende GG, Meirelles EDS, Marques CDL, Chiereghin A, Lyrio AM, Ximenes AC, Saad CG, Gonçalves CR, Kohem CL, Schainberg CG, Campanholo CB, Bueno Filho JSDS, Pieruccetti LB, Keiserman MW, Yazbek MA, Palominos PE, Goncalves RSG, Lage RDC, Assad RL, Bonfiglioli R, Anti SMA, Carneiro S, Oliveira TL, Azevedo VF, Bianchi WA, Bernardo WM, Pinheiro MDM, Sampaio-Barros PD. The Brazilian Society of Rheumatology guidelines for axial spondyloarthritis - 2019. Adv Rheumatol 2020; 60:19. [PMID: 32171329 DOI: 10.1186/s42358-020-0116-2] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2019] [Accepted: 01/22/2020] [Indexed: 12/13/2022] Open
Abstract
Spondyloarthritis is a group of chronic inflammatory systemic diseases characterized by axial and/or peripheral joints inflammation, as well as extra-articular manifestations. The classification axial spondyloarthritis is adopted when the spine and/or the sacroiliac joints are predominantly involved. This version of recommendations replaces the previous guidelines published in May 2013.A systematic literature review was performed, and two hundred thirty-seven studies were selected and used to formulate 29 recommendations answering 15 clinical questions, which were divided into four sections: diagnosis, non-pharmacological therapy, conventional drug therapy and biological therapy. For each recommendation the level of evidence supporting (highest available), the strength grade according to Oxford, and the degree of expert agreement (inter-rater reliability) is informed.These guidelines bring evidence-based information on clinical management of axial SpA patients, including, diagnosis, treatment, and prognosis.
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Affiliation(s)
- Gustavo Gomes Resende
- Universidade Federal de Minas Gerais (UFMG), Alameda Álvaro Celso, 175 / 2° Andar. Santa Efigênia. CEP 30.150-260, Belo Horizonte, MG, Brazil.
| | | | | | | | - Andre Marun Lyrio
- Pontifície Universidade Católica (PUC) de Campinas, Campinas, Brazil
| | | | | | | | | | | | | | | | | | | | | | | | | | - Ricardo da Cruz Lage
- Universidade Federal de Minas Gerais (UFMG), Alameda Álvaro Celso, 175 / 2° Andar. Santa Efigênia. CEP 30.150-260, Belo Horizonte, MG, Brazil
| | | | | | | | - Sueli Carneiro
- Universidade Federal do Rio De Janeiro (UFRJ), Rio de Janeiro, Brazil
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16
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Kiltz U, Braun J, Becker A, Chenot JF, Dreimann M, Hammel L, Heiligenhaus A, Hermann KG, Klett R, Krause D, Kreitner KF, Lange U, Lauterbach A, Mau W, Mössner R, Oberschelp U, Philipp S, Pleyer U, Rudwaleit M, Schneider E, Schulte TL, Sieper J, Stallmach A, Swoboda B, Winking M. [Long version on the S3 guidelines for axial spondyloarthritis including Bechterew's disease and early forms, Update 2019 : Evidence-based guidelines of the German Society for Rheumatology (DGRh) and participating medical scientific specialist societies and other organizations]. Z Rheumatol 2020; 78:3-64. [PMID: 31784900 DOI: 10.1007/s00393-019-0670-3] [Citation(s) in RCA: 33] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Affiliation(s)
- U Kiltz
- Rheumazentrum Ruhrgebiet, Ruhr-Universität Bochum, Claudiusstr. 45, 44649, Herne, Deutschland.
| | - J Braun
- Rheumazentrum Ruhrgebiet, Ruhr-Universität Bochum, Claudiusstr. 45, 44649, Herne, Deutschland
| | | | - A Becker
- Allgemeinmedizin, präventive und rehabilitative Medizin, Universität Marburg, Karl-von-Frisch-Str. 4, 35032, Marburg, Deutschland
| | | | - J-F Chenot
- Universitätsmedizin Greifswald, Fleischmann Str. 6, 17485, Greifswald, Deutschland
| | - M Dreimann
- Zentrum für Operative Medizin, Klinik und Poliklinik für Unfall‑, Hand- und Wiederherstellungschirurgie, Universitätsklinikum Hamburg-Eppendorf (UKE), Martinistraße 52, 20251, Hamburg, Deutschland
| | | | - L Hammel
- Geschäftsstelle des Bundesverbandes der DVMB, Metzgergasse 16, 97421, Schweinfurt, Deutschland
| | | | - A Heiligenhaus
- Augenzentrum und Uveitis-Zentrum, St. Franziskus Hospital, Hohenzollernring 74, 48145, Münster, Deutschland
| | | | - K-G Hermann
- Institut für Radiologie, Charité Berlin, Charitéplatz 1, 10117, Berlin, Deutschland
| | | | - R Klett
- Praxis Manuelle & Osteopathische Medizin, Fichtenweg 17, 35428, Langgöns, Deutschland
| | | | - D Krause
- , Friedrich-Ebert-Str. 2, 45964, Gladbeck, Deutschland
| | - K-F Kreitner
- Klinik und Poliklinik für Diagnostische und Interventionelle Radiologie, Universitätsmedizin Mainz, Langenbeckstr. 1, 55131, Mainz, Deutschland
| | - U Lange
- Kerckhoff-Klinik, Rheumazentrum, Osteologie & Physikalische Medizin, Benekestr. 2-8, 61231, Bad Nauheim, Deutschland
| | | | - A Lauterbach
- Schule für Physiotherapie, Orthopädische Universitätsklinik Friedrichsheim, Marienburgstraße 2, 60528, Frankfurt, Deutschland
| | | | - W Mau
- Institut für Rehabilitationsmedizin, Medizinische Fakultät, Martin-Luther-Universität Halle-Wittenberg, 06097, Halle (Saale), Deutschland
| | - R Mössner
- Klinik für Dermatologie, Universitätsmedizin Göttingen, Robert-Koch-Straße 40, 37075, Göttingen, Deutschland
| | | | - U Oberschelp
- , Barlachstr. 6, 59368, Werne a.d. L., Deutschland
| | | | - S Philipp
- Praxis für Dermatologie, Bernauer Str. 66, 16515, Oranienburg, Deutschland
| | - U Pleyer
- Campus Virchow-Klinikum, Charité Centrum 16, Klinik f. Augenheilkunde, Charité, Augustenburger Platz 1, 13353, Berlin, Deutschland
| | - M Rudwaleit
- Klinikum Bielefeld, An der Rosenhöhe 27, 33647, Bielefeld, Deutschland
| | - E Schneider
- Abt. Fachübergreifende Frührehabilitation und Sportmedizin, St. Antonius Hospital, Dechant-Deckersstr. 8, 52249, Eschweiler, Deutschland
| | - T L Schulte
- Klinik für Orthopädie und Unfallchirurgie, Orthopädische Universitätsklinik, Ruhr-Universität Bochum, Gudrunstr. 65, 44791, Bochum, Deutschland
| | - J Sieper
- Medizinische Klinik für Gastroenterologie, Infektiologie und Rheumatologie, Charité - Universitätsmedizin Berlin, Hindenburgdamm 30, 12203, Berlin, Deutschland
| | - A Stallmach
- Klinik für Innere Medizin IV, Universitätsklinikum Jena, Am Klinikum 1, 07743, Jena, Deutschland
| | | | - B Swoboda
- Abteilung für Orthopädie und Rheumatologie, Orthopädische Universitätsklinik, Malteser Waldkrankenhaus St. Marien, 91054, Erlangen, Deutschland
| | | | - M Winking
- Zentrum für Wirbelsäulenchirurgie, Klinikum Osnabrück, Am Finkenhügel 3, 49076, Osnabrück, Deutschland
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17
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Qin J, Li J, Yang H, Jia M, Li X, Yao Q, Zhang Y, Zhu J, Li C. Values of intravoxel incoherent motion diffusion weighted imaging and dynamic contrast-enhanced MRI in evaluating the activity of sacroiliitis in ankylosing spondylitis of rat model. Magn Reson Imaging 2020; 68:30-35. [PMID: 31978516 DOI: 10.1016/j.mri.2020.01.007] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2019] [Revised: 11/22/2019] [Accepted: 01/19/2020] [Indexed: 12/27/2022]
Abstract
OBJECTIVE To prospectively evaluate the ability of IVIM-DWI and DCE-MRI in detecting early activity of sacroiliitis in rat model of ankylosing spondylitis by comparing with pathological results. METHODS 20 wistar male rats were induced by bovine proteoglycan combined with complete/incomplete Freund's adjuvant as model group, and 20 healthy male rats were used as the control group. The parameters of IVIM-DWI and DCE-MRI in synovial regions of SIJ were measured respectively at 7th, 12th, 17th, and 22th weeks after the last induction, and the pathological features of SIJ were taken also, further studying the pathological characteristics of sacroiliac region. Independent sample t-test and one-way ANOVA were used for statistical analysis. The prediction parameters and diagnostic efficiency were compared by ROC curve. RESULTS There was no significant difference of image parameters between the model and control groups at the 7th, 12th weeks after the last induction, and there were no positive findings in histopathological examination at the same time. At the 17th week after induction, the f and Fenh%, Senh% between the model and the control groups were statistically significant. At the 22th week, there was a statistically significant increase all the values in model group than those in control group (P < 0.05). Histologic examination confirmed inflmmtorycell infiitrtion at the 17th week and pannus forming of synovium on the surface of cartilage at the 22th week in the model groups. The Fenh%, Senh%, Dslow and f had the moderate diagnostic efficiency and the areas under the curve were 0.77, 0.75, 0.77 and 0.82 respectively. The Senh% demonstrated the highest sensitivity (71.4%) and f demonstrated the highest specificity (95.0%). CONCLUSION IVIM-DWI and DCE-MRI can be used as the sensitive imaging methods to detect and accurate diagnosis the early activity of sacroiliitis in AS.
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Affiliation(s)
- Jian Qin
- Department of Radiology, The Second Affiliated Hospital of Shandong First Medical University, Tai'an, Shandong 271000, China
| | - Jiang Li
- Department of Radiology, The Second Affiliated Hospital of Shandong First Medical University, Tai'an, Shandong 271000, China
| | - Hui Yang
- Department of Radiology, The Second Affiliated Hospital of Shandong First Medical University, Tai'an, Shandong 271000, China
| | - Mingsheng Jia
- Department of Radiology, The Second Affiliated Hospital of Shandong First Medical University, Tai'an, Shandong 271000, China
| | - Xiaoqian Li
- Department of Radiology, The Second Affiliated Hospital of Shandong First Medical University, Tai'an, Shandong 271000, China
| | - Qianqian Yao
- Department of Radiology, The Second Affiliated Hospital of Shandong First Medical University, Tai'an, Shandong 271000, China
| | - Yue Zhang
- Department of Radiology, The Second Affiliated Hospital of Shandong First Medical University, Tai'an, Shandong 271000, China
| | - Jianzhong Zhu
- Department of Radiology, The Second Affiliated Hospital of Shandong First Medical University, Tai'an, Shandong 271000, China
| | - Changqin Li
- Department of Radiology, The Second Affiliated Hospital of Shandong First Medical University, Tai'an, Shandong 271000, China.
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18
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Disease Activity, Occupational Participation, and Quality of Life for Individuals with and without Severe Fatigue in Ankylosing Spondylitis. Occup Ther Int 2019; 2019:3027280. [PMID: 31354395 PMCID: PMC6636565 DOI: 10.1155/2019/3027280] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2018] [Revised: 03/24/2019] [Accepted: 04/11/2019] [Indexed: 01/21/2023] Open
Abstract
Background Fatigue is one of the most frequently reported symptoms by individuals with ankylosing spondylitis. However, it is often overlooked clinically and in research. Literature researching the impact of severe fatigue on occupational participation in ankylosing spondylitis is limited. Therefore, the aim of this research was to explore the impact of severe fatigue on occupational participation, disease activity, and quality of life in people with AS. Methods A sequential exploratory mixed method study design was used in this study. Self-reported questionnaires gathered quantitative data which were analysed with descriptive and inferential statistics. Qualitative data were generated through semistructured interviews and analysed using a content analysis approach. Results Fifty individuals with AS completed all study questionnaires. Participants had a mean age of 46.5 years; 72% were men with a mean disease duration of 14.5 years. High fatigue was reported by 38% of participants using the Multidimensional Assessment of Fatigue (MAF). Fatigue was significantly associated with lower occupational participation (p = 0.018), higher disease activity (p < 0.001), higher pain (p < 0.001), reduced physical capacity (p = 0.018), lower quality of life (p < 0.001), and lower global well-being (p < 0.001). There were significant differences between those with low and high fatigue levels for occupational participation (p = 0.007), disease activity (p < 0.001), physical capacity (p = 0.015), pain (p < 0.001), and quality of life (p < 0.001). Participants discussed the impact of fatigue on productivity and leisure. They also discussed a range of strategies for managing their fatigue but reported a lack of education from health professionals on managing this symptom. Conclusion Severe fatigue is a prevalent symptom for individuals with ankylosing spondylitis and results in reduced occupational participation in productivity and leisure. Early fatigue management interventions may reduce the occupational participation impact of this symptom for individuals with ankylosing spondylitis.
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Wink F, Arends S, Maas F, Bootsma H, Griep EN, Bruyn GAW, Spoorenberg A. High prevalence of hip involvement and decrease in inflammatory ultrasound lesions during tumour necrosis factor-α blocking therapy in ankylosing spondylitis. Rheumatology (Oxford) 2019; 58:1040-1046. [PMID: 30624693 DOI: 10.1093/rheumatology/key382] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/08/2018] [Revised: 10/03/2018] [Indexed: 12/25/2022] Open
Affiliation(s)
- Freke Wink
- 1Rheumatology, Medical Center Leeuwarden, Leeuwarden, The Netherlands
| | - Suzanne Arends
- Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Fiona Maas
- Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Hendrika Bootsma
- Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
| | - Ed N Griep
- Rheumatology, Antonius Hospital, Sneek, The Netherlands
| | | | - Anneke Spoorenberg
- Rheumatology and Clinical Immunology, University of Groningen, University Medical Center Groningen, Groningen, The Netherlands
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Factors Associated With Initiation of Biologics in Patients With Axial Spondyloarthritis in an Urban Asian City: A PRESPOND Study. J Clin Rheumatol 2018; 25:59-64. [PMID: 29667943 DOI: 10.1097/rhu.0000000000000762] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Abstract
OBJECTIVE The aim of this study was to examine if patients' sociodemographic, clinical characteristics, and patient-reported outcomes were associated with biologics initiation in patients with axial spondyloarthritis in Singapore. METHODS Data from a dedicated registry from a tertiary referral center in Singapore from January 2011 to July 2016 were used. Initiation of first biologics was the main outcome of interest. Logistic regression analyses were used to explore the association of various factors on biologics initiation. RESULTS Of 189 eligible patients (aged 37.7 ± 13.3 years; 76.2% were males), 30 (15.9 %) were started on biologics during follow-up. In the multivariable analysis model, age (odds ratio [OR]; 0.93; 95% confidence interval [CI], 0.89-0.98; p < 0.01), mental component summary score of Short-Form 36 Health Survey (OR, 0.18; 95% CI, 0.03-0.89; p = 0.04), erythrocyte sedimentation rate (OR, 1.02; 95% CI, 1.00-1.04; p = 0.02), presence of peptic ulcer disease (OR, 10.4; 95% CI, 2.21-48.8; p < 0.01), and lack of good response to nonsteroidal anti-inflammatory drugs (OR, 4.44; 95% CI, 1.63-12.1; p < 0.01) were found to be associated with biologics initiation. CONCLUSIONS Age, erythrocyte sedimentation rate, mental component summary score, comorbidities of peptic ulcer disease, and responsiveness to nonsteroidal anti-inflammatory drugs were associated with biologics initiation. It is essential that clinicians recognize these factors in order to optimize therapy.
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Webers C, Essers I, van Tubergen A, Braun J, Heldmann F, Baraliakos X, Boonen A. Valuing Treatment With Infliximab for Ankylosing Spondylitis Using a Willingness-to-Pay Approach. Arthritis Care Res (Hoboken) 2018; 70:608-616. [PMID: 28575536 PMCID: PMC5901401 DOI: 10.1002/acr.23299] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2016] [Accepted: 06/01/2017] [Indexed: 01/17/2023]
Abstract
OBJECTIVE To investigate willingness to pay (WTP) for treatment with infliximab by patients with ankylosing spondylitis (AS) and explore factors associated with WTP. METHODS Data from 85 patients participating in the European AS Infliximab Cohort (EASIC) open-label extension of the AS Study for the Evaluation of Recombinant Infliximab Therapy (ASSERT) were used. WTP was included at baseline in EASIC and comprised a hypothetical scenario exploring whether the patient would be willing to pay for beneficial effects of infliximab and, if so, what amount they would be willing to pay per administration. Factors associated with WTP were explored using zero-inflated negative binomial (ZINB) regressions. RESULTS Of the 85 patients, 63 (74.1%) were willing to pay, and among these, the mean amount they were willing to pay per administration was €275 (median €100 [interquartile range €50-200]). Multivariable ZINB analysis showed that Assessment of SpondyloArthritis international Society criteria for 20% improvement (ASAS20) response was associated with a 7-fold lower likelihood to pay 0 euros (odds ratio [OR] 0.14 [95% confidence interval (95% CI) 0.03-0.71]) and a 3-fold increase in the amount willing to pay (exp(β) = 3.32 [95% CI 1.44-7.69]). In addition, the country of residence was associated with a lower likelihood to pay 0 euros (OR 0.07 [95% CI 0.02-0.36]), while increased age was associated with the amount willing to pay (exp(β) = 1.05 [95% CI 1.01-1.09]). CONCLUSION In a hypothetical scenario, three-quarters of patients with AS receiving long-term infliximab stated that they were willing to pay an out-of-pocket contribution for this treatment. Treatment response contributed to the willingness as well as to the amount patients were willing to pay.
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Affiliation(s)
- Casper Webers
- Maastricht University Medical Center and School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, The Netherlands
| | - Ivette Essers
- Maastricht University Medical Center and School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, The Netherlands
| | - Astrid van Tubergen
- Maastricht University Medical Center and School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, The Netherlands
| | | | | | | | - Annelies Boonen
- Maastricht University Medical Center and School for Public Health and Primary Care (CAPHRI), Maastricht University, Maastricht, The Netherlands
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Fudman DI, Flier SN. Anti-TNF Therapy for Treatment of Extraintestinal Manifestations of Inflammatory Bowel Disease. TREATMENT OF INFLAMMATORY BOWEL DISEASE WITH BIOLOGICS 2018:49-57. [DOI: 10.1007/978-3-319-60276-9_4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Assessment of Correlation between Intravoxel Incoherent Motion Diffusion Weighted MR Imaging and Dynamic Contrast-Enhanced MR Imaging of Sacroiliitis with Ankylosing Spondylitis. BIOMED RESEARCH INTERNATIONAL 2017; 2017:8135863. [PMID: 29445743 PMCID: PMC5763214 DOI: 10.1155/2017/8135863] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/22/2017] [Revised: 11/07/2017] [Accepted: 12/03/2017] [Indexed: 12/18/2022]
Abstract
The relationships between IVIM and DCE-MRI parameters in AS are not clear. We explore the correlation between intravoxel incoherent motion (IVIM) diffusion weighted imaging (DWI) and dynamic contrast-enhanced (DCE) parameters obtained on MR images in patients with ankylosing spondylitis (AS). Forty-four patients with AS were prospectively examined using a 1.5-T MR system. IVIM DWI was performed with 11 b values (range, 0–800 s/mm2) for all patients. The correlation coefficients between IVIM and DCE-MRI parameters were analyzed using Spearman's method. Our results showed that intra- and interobserver reproducibility were excellent to relatively good (ICC = 0.804–0.981; narrow width of 95% limits of agreement). Moderate positive correlations were observed between pure molecular diffusion (Ds) and maximum enhancement (ME) and relative enhancement (RE) (r = 0.700, P < 0.001; r = 0.607, P < 0.001, resp.). Perfusion-related diffusion (Df) showed negative moderate correlation with ME (r = −0.608, P < 0.001). However, no correlation was observed between perfusion fraction (f) and any parameters of ME, RE, TTP, and BE (r = −0.093–0.213; P > 0.165). In conclusion, the IVIM parameters, especially f, might play a critical role in detecting the progression of AS, because it can provide more perfusion information compared with DCE-MRI; besides the IVIM MRI is a noninvasive method.
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Wang CR, Weng CT, Lee CT, Huang KY, Hsu SM, Liu MF. Rare occurrence of inflammatory bowel disease in a cohort of Han Chinese ankylosing spondylitis patients- a single institute study. Sci Rep 2017; 7:13165. [PMID: 29030592 PMCID: PMC5640612 DOI: 10.1038/s41598-017-13573-z] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/21/2017] [Accepted: 09/25/2017] [Indexed: 02/07/2023] Open
Abstract
Despite a high prevalence of ankylosing spondylitis (AS) in Han Chinese, the clinical experience remains very limited in the extra-articular presentation of inflammatory bowel disease (IBD). A monocentric retrospective study was performed for the AS-associated IBD manifestation. This study analyzed AS patients fulfilling the 1984 revised New York diagnostic criteria, excluding those who had the onset of IBD before or concurrently with the diagnosis of AS, for their demographic, clinical, laboratory, radiological, pathological and medication data, particularly in the usage of anti-TNF monoclonal antibody. Among 988 AS patients with 19.8% female, 4 (0.4%) had the overt IBD presentation, one female and 3 male aged 28 to 47 years (38.8 ± 4.6), all ulcerative colitis with the characteristic histopathological findings. At the onset of colitis, all had a long-term disease duration of 10 to 25 years (17.5 ± 6.5) and high BASDAI 7.5 to 8.8 (8.2 ± 0.5) with the hip joint involvement. There were recurrent flares of colitis despite the treatment with corticosteroids and messalazopyrin/salazopyrin, and no relapses of IBD were observed for 6.0 ± 1.1 years after the adalimumab (ADA) therapy. In this retrospective cohort, we demonstrate the rarity of AS-associated IBD manifestation in Han Chinese with a beneficent effect from the ADA therapy.
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Affiliation(s)
- Chrong-Reen Wang
- Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan.
| | - Chia-Tse Weng
- Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Chung-Ta Lee
- Pathology, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Kuo-Yuan Huang
- Orthopaedics, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Sheng-Min Hsu
- Opthalmology, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Ming-Fei Liu
- Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
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van der Heijde D, Dougados M, Landewé R, Sieper J, Maksymowych WP, Rudwaleit M, Van den Bosch F, Braun J, Mease PJ, Kivitz AJ, Walsh J, Davies O, Bauer L, Hoepken B, Peterson L, Deodhar A. Sustained efficacy, safety and patient-reported outcomes of certolizumab pegol in axial spondyloarthritis: 4-year outcomes from RAPID-axSpA. Rheumatology (Oxford) 2017; 56:1498-1509. [PMID: 28498975 PMCID: PMC5850296 DOI: 10.1093/rheumatology/kex174] [Citation(s) in RCA: 64] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/23/2017] [Indexed: 02/07/2023] Open
Abstract
Objective The aim was to assess the long-term safety and efficacy of certolizumab pegol over 4 years of continuous treatment in patients with axial spondyloarthritis (axSpA), including both AS and non-radiographic (nr-) axSpA. Methods RAPID-axSpA was a phase 3 randomized trial, double blind and placebo controlled to week 24, dose blind to week 48 and open label to week 204. Patients had a clinical diagnosis of axSpA, meeting Assessment of SpondyloArthritis international Society (ASAS) criteria, and had active disease. The assessed outcomes included ASAS20, ASAS40, AS DAS (ASDAS), BASDAI, BASFI and BASMI scores, along with selected measures of remission. Further patient-reported outcomes, peripheral arthritis, enthesitis, uveitis and quality-of-life measures are also reported. Results Two hundred and eighteen of 325 patients randomized (AS: 121; nr-axSpA: 97) received certolizumab pegol from week 0. Of these, 65% remained in the study at week 204 (AS: 67%; nr-axSpA: 63%). Across all outcomes, for AS and nr-axSpA, sustained improvements were observed to week 204 [week 204 overall axSpA: ASAS20: 54.1% (non-responder imputation); 83.7% (observed case, OC); ASAS40: 44.0% (non-responder imputation); 68.1% (OC); ASDAS inactive disease: 32.1% (last observation carried forward); 31.4% (OC)]. In the safety set (n = 315), there were 292.8 adverse events and 10.4 serious adverse events per 100 patient-years. No deaths were reported. Conclusion In the first study to evaluate the efficacy of an anti-TNF across both axSpA subpopulations, improvements in clinical and patient-reported outcomes at 24 and 96 weeks were sustained through 4 years of treatment, with no new safety signals. Trial registration ClinicalTrials.gov, http://clinicaltrials.gov, NCT01087762.
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Affiliation(s)
| | | | - Robert Landewé
- Clinical Immunology and Rheumatology, Academic Medical Center, Amsterdam.,Department of Rheumatology, Zuyderland Medical Center, Heerlen, The Netherlands
| | - Joachim Sieper
- Rheumatology Department, Charité - University Medicine, Berlin, Germany
| | | | - Martin Rudwaleit
- Department of Internal Medicine and Rheumatology, Klinikum Bielefeld, Bielefeld, Germany
| | | | | | - Philip J Mease
- Swedish Medical Center, University of Washington, Seattle, WA
| | - Alan J Kivitz
- Altoona Center for Clinical Research, Duncansville, PA
| | - Jessica Walsh
- Division of Rheumatology, University of Utah School of Medicine, Salt Lake City, UT, USA
| | | | | | | | | | - Atul Deodhar
- Division of Arthritis and Rheumatic Diseases, Oregon Health & Science University, Portland, OR, USA
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Harmonization of Infliximab and Anti-Infliximab Assays Facilitates the Comparison Between Originators and Biosimilars in Clinical Samples. Inflamm Bowel Dis 2016; 22:969-75. [PMID: 26954707 DOI: 10.1097/mib.0000000000000709] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
BACKGROUND The availability of an infliximab ELISA for measuring the originator drug Remicade and its biosimilars, such as Remsima and Inflectra (CT-P13), would facilitate the implementation of therapeutic drug monitoring of biosimilars and enhance the extrapolation of treatment stratification algorithms established for Remicade. A universal calibrator for all anti-infliximab antibody bridging assays allows harmonization of anti-drug antibody titers. METHODS A panel of 55 mouse monoclonal antibodies raised against Remicade, including MA-IFX6B7 and MA-IFX10F9, were evaluated for their reactivity toward the biosimilars using a sandwich-type ELISA and surface plasmon resonance. To analyze the similarity of detection of the biosimilars and Remicade in the infliximab ELISA, quality control samples were used. Bridging assays to determine anti-infliximab antibodies were developed according to the bridging ELISA of Remicade using MA-IFX10F9 as calibrator. Serum of 36 patients treated with Remicade was analyzed for anti-infliximab antibodies toward Remicade, Remsima and Inflectra using their respective bridging ELISA. RESULTS MA-IFX6B7 and MA-IFX10F9 exhibit equal reactivity toward Remicade, Remsima, and Inflectra. The infliximab ELISA quantifies the biosimilars equally well as Remicade. Quantification of anti-infliximab antibodies in the serum of patients treated with Remicade revealed highly correlated titers between biosimilars and Remicade. CONCLUSIONS The assay for therapeutic drug monitoring of Remicade can also be used to determine Remsima and Inflectra concentrations. Anti-drug antibody assays for biosimilars were developed. Anti-Remicade antibodies cross-react with infliximab biosimilars and reveal consistent negative/positive anti-drug antibody responses and highly correlated titers.
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López-Medina C, Schiotis RE, Font-Ugalde P, Castro-Villegas MC, Calvo-Gutiérrez J, Ortega-Castro R, Jiménez-Gasco R, Escudero-Contreras A, Collantes-Estévez E. Assessment of Fatigue in Spondyloarthritis and Its Association with Disease Activity. J Rheumatol 2016; 43:751-7. [DOI: 10.3899/jrheum.150832] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 12/18/2015] [Indexed: 01/28/2023]
Abstract
Objective.To evaluate fatigue in patients with spondyloarthritis (SpA) and to define its association with disease-related factors and patients’ features.Methods.A cross-sectional multicenter study which includes 2251 patients with SpA selected from the national Spondyloarthropathies Registry (the Spanish Society of Rheumatology; REGISPONSER) Spanish cohort. The primary outcome was the assessment of fatigue performed with the first item of the Bath Ankylosing Spondyloarthritis Disease Activity Index followed by the study of its relation with different factors organized into 4 groups: sociodemographics, emotional, disease-related, and disease activity. Univariate logistic regressions, multivariate logistic regression, and multiple linear regressions were performed to relate fatigue with the studied covariates.Results.Mean fatigue score in all patients with SpA was 4.3 ± 2.9, with statistically significant differences between different SpA types. In univariate logistic regressions, significant differences were seen for many variables included in the 4 groups. Multivariate logistic regression showed that high fatigue score was related with sex (female), emotional component, the Ankylosing Spondylitis Quality of Life score, stiffness, and high levels of 2 visual analog scale items (vertebral pain in the last week and patient’s global assessment of disease activity). The multivariate linear regression showed that fatigue was mainly explained by disease-related factors and disease activity (54.1%), but sex and emotional status may also be involved in 13.5% of the variance.Conclusion.Fatigue is associated with disease-related factors and mostly with SpA activity. However, the emotional component and sex may contribute to the onset of fatigue.
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Corbett M, Soares M, Jhuti G, Rice S, Spackman E, Sideris E, Moe-Byrne T, Fox D, Marzo-Ortega H, Kay L, Woolacott N, Palmer S. Tumour necrosis factor-α inhibitors for ankylosing spondylitis and non-radiographic axial spondyloarthritis: a systematic review and economic evaluation. Health Technol Assess 2016; 20:1-334, v-vi. [PMID: 26847392 PMCID: PMC4781282 DOI: 10.3310/hta20090] [Citation(s) in RCA: 56] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
BACKGROUND Tumour necrosis factor (TNF)-α inhibitors (anti-TNFs) are typically used when the inflammatory rheumatologic diseases ankylosing spondylitis (AS) and non-radiographic axial spondyloarthritis (nr-AxSpA) have not responded adequately to conventional therapy. Current National Institute for Health and Care Excellence (NICE) guidance recommends treatment with adalimumab, etanercept and golimumab in adults with active (severe) AS only if certain criteria are fulfilled but it does not recommend infliximab for AS. Anti-TNFs for patients with nr-AxSpA have not previously been appraised by NICE. OBJECTIVE To determine the clinical effectiveness, safety and cost-effectiveness within the NHS of adalimumab, certolizumab pegol, etanercept, golimumab and infliximab, within their licensed indications, for the treatment of severe active AS or severe nr-AxSpA (but with objective signs of inflammation). DESIGN Systematic review and economic model. DATA SOURCES Fifteen databases were searched for relevant studies in July 2014. REVIEW METHODS Clinical effectiveness data from randomised controlled trials (RCTs) were synthesised using Bayesian network meta-analysis methods. Results from other studies were summarised narratively. Only full economic evaluations that compared two or more options and considered both costs and consequences were included in the systematic review of cost-effectiveness studies. The differences in the approaches and assumptions used across the studies, and also those in the manufacturer's submissions, were examined in order to explain any discrepancies in the findings and to identify key areas of uncertainty. A de novo decision model was developed with a generalised framework for evidence synthesis that pooled change in disease activity (BASDAI and BASDAI 50) and simultaneously synthesised information on function (BASFI) to determine the long-term quality-adjusted life-year and cost burden of the disease in the economic model. The decision model was developed in accordance with the NICE reference case. The model has a lifetime horizon (60 years) and considers costs from the perspective of the NHS and personal social services. Health effects were expressed in terms of quality-adjusted life-years. RESULTS In total, 28 eligible RCTs were identified and 26 were placebo controlled (mostly up to 12 weeks); 17 extended into open-label active treatment-only phases. Most RCTs were judged to have a low risk of bias overall. In both AS and nr-AxSpA populations, anti-TNFs produced clinically important benefits to patients in terms of improving function and reducing disease activity; for AS, the relative risks for ASAS 40 ranged from 2.53 to 3.42. The efficacy estimates were consistently slightly smaller for nr-AxSpA than for AS. Statistical (and clinical) heterogeneity was more apparent in the nr-AxSpA analyses than in the AS analyses; both the reliability of the nr-AxSpA meta-analysis results and their true relevance to patients seen in clinical practice are questionable. In AS, anti-TNFs are approximately equally effective. Effectiveness appears to be maintained over time, with around 50% of patients still responding at 2 years. Evidence for an effect of anti-TNFs delaying disease progression was limited; results from ongoing long-term studies should help to clarify this issue. Sequential treatment with anti-TNFs can be worthwhile but the drug survival response rates and benefits are reduced with second and third anti-TNFs. The de novo model, which addressed many of the issues of earlier evaluations, generated incremental cost-effectiveness ratios ranging from £19,240 to £66,529 depending on anti-TNF and modelling assumptions. CONCLUSIONS In both AS and nr-AxSpA populations anti-TNFs are clinically effective, although more so in AS than in nr-AxSpA. Anti-TNFs may be an effective use of NHS resources depending on which assumptions are considered appropriate. FUTURE WORK RECOMMENDATIONS Randomised trials are needed to identify the nr-AxSpA population who will benefit the most from anti-TNFs. STUDY REGISTRATION This study is registered as PROSPERO CRD42014010182. FUNDING The National Institute for Health Research Health Technology Assessment programme.
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Affiliation(s)
- Mark Corbett
- Centre for Reviews and Dissemination, University of York, York, UK
| | - Marta Soares
- Centre for Health Economics, University of York, York, UK
| | - Gurleen Jhuti
- Centre for Health Economics, University of York, York, UK
| | - Stephen Rice
- Centre for Reviews and Dissemination, University of York, York, UK
| | - Eldon Spackman
- Centre for Health Economics, University of York, York, UK
| | | | | | - Dave Fox
- Centre for Reviews and Dissemination, University of York, York, UK
| | - Helena Marzo-Ortega
- Division of Rheumatic and Musculoskeletal Disease, Chapel Allerton Hospital, Leeds Teaching Hospitals NHS Trust and University of Leeds, Leeds, UK
| | - Lesley Kay
- Division of Rheumatic and Musculoskeletal Disease, Chapel Allerton Hospital, Leeds Teaching Hospitals NHS Trust and University of Leeds, Leeds, UK
| | - Nerys Woolacott
- Centre for Reviews and Dissemination, University of York, York, UK
| | - Stephen Palmer
- Centre for Health Economics, University of York, York, UK
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Tran-Duy A, Boonen A, van de Laar MAFJ, Severens JL. Impact on total population health and societal cost, and the implication on the actual cost-effectiveness of including tumour necrosis factor-α antagonists in management of ankylosing spondylitis: a dynamic population modelling study. COST EFFECTIVENESS AND RESOURCE ALLOCATION 2015; 13:18. [PMID: 26451133 PMCID: PMC4597433 DOI: 10.1186/s12962-015-0044-x] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/29/2014] [Accepted: 09/29/2015] [Indexed: 12/30/2022] Open
Abstract
Background Sequential treatment of ankylosing spondylitis (AS) that includes tumour necrosis factor-α antagonists (anti-TNF agents) has been applied in most of the Western countries. Existing cost-effectiveness (CE) models almost exclusively presented the incremental CE of anti-TNF agents using a closed cohort while budget impact studies are mainly lacking. Notwithstanding, information on impact on total population health and societal budget as well as on actual incremental CE for a given decision time span are important for decision makers. This study aimed at quantifying, for different decision time spans starting from January 1, 2014 in the Dutch society, (1) impact of sequential drug treatment strategies without and with inclusion of anti-TNF agents (Strategies 1 and 2, respectively) on total population health and societal cost, and (2) the actual incremental CE of Strategy 2 compared to Strategy 1. Methods Dynamic population modelling was used to capture total population health and cost, and the actual incremental CE. Distinguishing the prevalent AS population on January 1, 2014 and the incident AS cohorts in the subsequent 20 years, the model tracked individually an actual number of AS patients until death or end of the simulation time. During the simulation, data on patient characteristics, history of drug use, costs and health at discrete time points were generated. In Strategy 1, five nonsteroidal anti-inflammatory drugs (NSAIDs) were available but anti-TNF agents withdrawn. In Strategy 2, five NSAIDs and two anti-TNF agents continued to be available. Results The predicted size of the prevalent AS population in the Dutch society varied within the range of 67,145–69,957 with 44–46 % of the patients receiving anti-TNF agents over the period 2014–2034. The use of anti-TNF agents resulted in an increase in the annual drug costs (168.54–205.28 million Euros), but at the same time caused a decrease in the annual productivity costs (12.58–31.21 million Euros) and in annual costs of healthcare categories other than drugs (7.23–11.90 million Euros). Incremental cost (Euros) per QALY gained in Strategy 2 compared to Strategy 1 corresponding to decision time spans of 5, 10, 15 and 20 years improved slightly from 75,379 to 67,268, 63,938 and 61,129, respectively. At willingness-to-pay thresholds of 118,656, 112,067, 110,188 and 110,512 Euros, it was 99 % certain that Strategy 2 was cost-effective for decision time spans of 5, 10, 15 and 20, respectively. Conclusions Using the dynamic population approach, the present model can project real-time data to inform a healthcare system decision that affects all actual number of AS patients eligible for anti-TNF agents within different decision time spans. The predicted total population costs of different categories in the present study can help plan the organization of the healthcare resources based on the national budget for the disease.
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Affiliation(s)
- An Tran-Duy
- Department of Clinical Epidemiology and Medical Technology Assessment, Maastricht University Medical Center, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands ; Division of Rheumatology, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands ; Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
| | - Annelies Boonen
- Division of Rheumatology, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands ; Caphri School for Public Health and Primary Care, Maastricht UMC+, Maastricht, The Netherlands
| | - Mart A F J van de Laar
- Department of Rheumatology and Clinical Immunology, Twente University and Medisch Spectrum Twente, Enschede, The Netherlands
| | - Johan L Severens
- Institute of Health Policy and Management, Erasmus University Rotterdam, Rotterdam, The Netherlands
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Abstract
The term axial spondyloarthritis covers both non-radiographic disease and radiographic disease (also known as ankylosing spondylitis). Some studies have been performed to investigate the prevalence of axial spondyloarthritis, although most are limited to patients with radiographic disease. A strong genetic association has been shown between axial spondyloarthritis and human leukocyte antigen-B27 (HLA-B27), but the pathogenetic role of HLA-B27 has not yet been clarified. Tumour necrosis factor (TNF), IL-17, IL-23 and downstream pathways also seem to be important - based on the good results of therapies directed against these molecules - but their exact role in the inflammatory process is also not yet clear. Elucidating the interaction between osteoproliferation and inflammation will be crucial for the prevention of long-term structural damage of the bone. The development of new criteria for classification, diagnosis and screening of patients with axial spondyloarthritis will enable earlier intervention for this chronic inflammatory disease. MRI has become an important tool for the early detection of axial spondyloarthritis. NSAIDs and TNF blockers are effective therapies, including in the early non-radiographic stage. Therapeutic blockade of IL-17 or IL-23 seems to be a promising new treatment option. Tools for measuring quality of life in axial spondyloarthritis have become relevant to assess the impact that the disease has on patients. These diagnostic and therapeutic advances will continue to change the management of axial spondyloarthritis, and new insights into the disease pathogenesis will hopefully accelerate this process. For an illustrated summary of this Primer, visit: http://go.nature.com/51b1af.
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Affiliation(s)
- Joachim Sieper
- Rheumatology, Charité, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany
| | | | - Maxime Dougados
- Faculty of Medicine, Paris Descartes University, Department of Rheumatology, Hôpital Cochin, Assistance Publique, Hôpitaux de Paris, INSERM (U1153), Clinical Epidemiology and Biostatistics, PRES Sorbonne Paris-Cité, Paris, France
| | - Dominique Baeten
- Clinical Immunology and Rheumatology and Amsterdam Rheumatology and Immunology Center, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
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Mease P, Sieper J, Van den Bosch F, Rahman P, Karunaratne PM, Pangan AL. Randomized controlled trial of adalimumab in patients with nonpsoriatic peripheral spondyloarthritis. Arthritis Rheumatol 2015; 67:914-23. [PMID: 25545240 PMCID: PMC4409087 DOI: 10.1002/art.39008] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/25/2013] [Accepted: 12/19/2014] [Indexed: 12/17/2022]
Abstract
OBJECTIVE To evaluate the efficacy and safety of adalimumab in patients with active nonpsoriatic peripheral spondyloarthritis (SpA). METHODS ABILITY-2 is an ongoing phase III, multicenter study of adalimumab treatment. Eligible patients age ≥18 years fulfilled the Assessment of SpondyloArthritis international Society (ASAS) classification criteria for peripheral SpA, did not have a prior diagnosis of psoriasis, psoriatic arthritis (PsA), or ankylosing spondylitis (AS), and had an inadequate response or intolerance to nonsteroidal antiinflammatory drugs (NSAIDs). Patients were randomized 1:1 to receive adalimumab 40 mg every other week or matching placebo for 12 weeks, followed by a 144-week open-label period. The primary end point was the proportion of patients achieving 40% improvement in disease activity according to the Peripheral SpA Response Criteria (PSpARC40) at week 12. This was defined as ≥40% improvement from baseline (≥20-mm absolute improvement on a visual analog scale) in patient's global assessments of disease activity and pain, and ≥40% improvement in at least one of the following features: swollen joint and tender joint counts, total enthesitis count, or dactylitis count. Adverse events were recorded throughout the study. RESULTS In total, 165 patients were randomized to a treatment group, of whom 81 were randomized to receive placebo and 84 to receive adalimumab. Baseline demographics and disease characteristics were generally similar between the 2 groups. At week 12, a greater proportion of patients receiving adalimumab achieved a PSpARC40 response compared to patients receiving placebo (39% versus 20%; P = 0.006). Overall, improvement in other outcomes was greater in the adalimumab group compared to the placebo group. The rates of adverse events were similar in both treatment groups. CONCLUSION Treatment with adalimumab ameliorated the signs and symptoms of disease and improved physical function in patients with active nonpsoriatic peripheral SpA who exhibited an inadequate response or intolerance to NSAIDs, with a safety profile consistent with that observed in patients with AS, PsA, or other immune-mediated diseases.
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Affiliation(s)
- Philip Mease
- Swedish Medical Center and University of WashingtonSeattle, Washington
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Detection of Active Sacroiliitis with Ankylosing Spondylitis through Intravoxel Incoherent Motion Diffusion-Weighted MR Imaging. Eur Radiol 2015; 25:2754-63. [PMID: 25678080 DOI: 10.1007/s00330-015-3634-2] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2014] [Revised: 01/10/2015] [Accepted: 01/21/2015] [Indexed: 12/16/2022]
Abstract
OBJECTIVE To confirm feasibility and assess intravoxel incoherent motion (IVIM) to differentiate active sacroiliitis and ankylosing spondylitis.. METHODS Forty-one patients were divided into two groups, an active group (n = 20) and a chronic group (n = 21), according to the Bath Ankylosing Spondylitis (AS) Disease Activity Index (BASDAI) and laboratory parameters. In addition, 21 healthy volunteers were chosen as the control group. Tissue diffusivity (Dslow), perfusion fraction (f), and pseudo-diffusion coefficient (Dfast) values were obtained for all three groups. One-way analysis of variance and receiver operating characteristic analysis were performed for all parameters. RESULTS There was good interobserver agreement on the measurements between the two observers. The optimal cut-off values (with respective AUC, sensitivity, specificity, positive likelihood ratio, and negative likelihood ratio) between active and chronic groups were Dslow = 0.53 × 10(-3) mm(2)/s (0.976, 90%, 95.2%, 18.9, 0.10) and f = 0.09 (0.545, 20%, 95.5%, 4.2, 0.84), and between chronic and control groups were Dslow = 0.22 × 10(-3) mm(2)/s (0.517, 9.52%, 100%, no number, 0.9) and f = 0.09 (0.935, 95.24%, 80.95%, 5, 0.059). CONCLUSION Dslow and f of IVIM diffusion-weighted (DW)-MRI in AS show a significant difference in the values of diffusion of water molecules and fractional perfusion-related volume among the three groups. KEY POINTS • D slow can be used to differentiate the activity of AS. • With perfusion fraction, the sensitivity of differentiating the AS activity is improved. • IVIM DWI plays an important role in detecting the activity in patients with AS.
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Coste E, Greig IR, Mollat P, Rose L, Gray M, Ralston SH, van 't Hof RJ. Identification of small molecule inhibitors of RANKL and TNF signalling as anti-inflammatory and antiresorptive agents in mice. Ann Rheum Dis 2015; 74:220-6. [PMID: 24095938 DOI: 10.1136/annrheumdis-2013-203700] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
INTRODUCTION Inflammatory joint diseases such as rheumatoid arthritis are associated with local bone erosions and systemic bone loss, mediated by increased osteoclastic activity. The receptor activator of nuclear factor (NF) κB ligand (RANKL) plays a key role in mediating inflammation-induced bone loss, whereas tumour necrosis factor (TNF) plays a central role in the inflammatory process. Here we tested whether a recently identified class of small molecule inhibitors of RANKL signalling (ABD compounds) also affect TNF signalling and whether these compounds inhibit inflammation in an animal model of rheumatoid arthritis. METHODS The inhibitory effects of the ABD compounds on TNF-induced signalling were tested in mouse macrophage cultures by western blotting and in an NFκB luciferase-reporter cell line. The anti-inflammatory effects of the compounds were tested in the mouse collagen-induced arthritis model of rheumatoid arthritis. RESULTS The ABD compounds ABD328 and ABD345 both inhibited TNF-induced activation of the NFκB pathway and the extracellular signal-regulated kinase (ERK) and Jun kinase (JNK) mitogen activated protein kinases (MAPKs). When tested in the mouse collagen-induced arthritis model of rheumatoid arthritis, the compounds suppressed inflammatory arthritis, inhibited joint destruction and prevented systemic bone loss. Furthermore, one of the compounds (ABD328) showed oral activity. CONCLUSIONS Here we describe a novel class of small molecule compounds that inhibit both RANKL- and TNF-induced NFκB and MAPK signalling in osteoclasts and macrophages, and inflammation and bone destruction in a mouse model of rheumatoid arthritis. These novel compounds therefore represent a promising new class of treatments for inflammatory diseases, such as rheumatoid arthritis.
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Affiliation(s)
- Emmanuel Coste
- Molecular Medicine Centre, Institute for Genetics and Molecular Medicine, University of Edinburgh, General Western Hospital, Edinburgh, UK
| | - Iain R Greig
- School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Aberdeen, UK
| | | | - Lorraine Rose
- Molecular Medicine Centre, Institute for Genetics and Molecular Medicine, University of Edinburgh, General Western Hospital, Edinburgh, UK
| | - Mohini Gray
- MRC Centre for Inflammation Research, The Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK
| | - Stuart H Ralston
- Molecular Medicine Centre, Institute for Genetics and Molecular Medicine, University of Edinburgh, General Western Hospital, Edinburgh, UK
| | - Rob J van 't Hof
- Molecular Medicine Centre, Institute for Genetics and Molecular Medicine, University of Edinburgh, General Western Hospital, Edinburgh, UK
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The SAPHO syndrome revisited with an emphasis on spinal manifestations. Skeletal Radiol 2015; 44:9-24. [PMID: 25331355 DOI: 10.1007/s00256-014-2025-0] [Citation(s) in RCA: 41] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2014] [Revised: 09/17/2014] [Accepted: 09/28/2014] [Indexed: 02/02/2023]
Abstract
The synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome includes a group of chronic, relapsing, inflammatory musculoskeletal disorders with similar manifestations, in particular synovitis, hyperostosis, and osteitis, which may or may not be associated with neutrophilic skin eruptions such as palmoplantar pustulosis and acne conglobata. The syndrome occurs at any age, can involve any skeletal site, and its imaging appearances are variable, depending on the stage/age of the lesion and imaging method. The diagnosis is difficult if there is no skin disease. Awareness of the imaging appearances, especially in the spine, may help the radiologist in avoiding misdiagnosis (e.g., infection, tumor) and unnecessary invasive procedures, while facilitating early diagnosis and selection of an effective treatment. In this article, we provide an overview of the radiological appearances of SAPHO syndrome, focusing on the magnetic resonance imaging findings of vertebral involvement, and present relevant clinical and pathological features that assist early diagnosis.
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van der Heijde D, Breban M, Halter D, DiVittorio G, Bratt J, Cantini F, Kary S, Pangan AL, Kupper H, Rathmann SS, Sieper J, Mease PJ. Maintenance of improvement in spinal mobility, physical function and quality of life in patients with ankylosing spondylitis after 5 years in a clinical trial of adalimumab. Rheumatology (Oxford) 2014; 54:1210-9. [PMID: 25541333 PMCID: PMC4473764 DOI: 10.1093/rheumatology/keu438] [Citation(s) in RCA: 41] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/11/2013] [Indexed: 12/25/2022] Open
Abstract
OBJECTIVE Chronic pain and progressive loss of physical function with AS may adversely affect health-related quality of life (HRQoL). The objective of this study was to assess the 5-year data regarding spinal mobility, physical function and HRQoL in patients with AS who participated in the Adalimumab Trial Evaluating Long-term Efficacy and Safety for AS (ATLAS) study. METHODS Patients received blinded adalimumab 40 mg or placebo every other week for 24 weeks, then open-label adalimumab for up to 5 years. Spinal mobility was evaluated using linear BASMI (BASMIlin). BASDAI, total back pain, CRP, BASFI, Short Form-36 and AS quality of life (ASQoL) were also assessed. Correlations between BASMIlin and clinical, functional and ASQoL outcomes after 12 weeks and after 5years of adalimumab exposure were evaluated using Spearman's rank correlation. Associations were further analysed using multivariate regression. RESULTS Three hundred and eleven patients received ≥1 dose of adalimumab; 125 of the 208 patients originally randomized to adalimumab received treatment for 5 years. Improvements in BASMIlin were sustained through 5 years, with a mean change of -0.6 from baseline in the population who completed 5 years of treatment with adalimumab. Improvements in disease activity, physical function and ASQoL were also sustained through 5 years. BASMIlin was significantly correlated with all evaluated clinical outcomes (P < 0.001). The highest correlation was with BASFI at 12 weeks (r = 0.52) and at 5 years (r = 0.65). Multivariate regression analysis confirmed this association (P < 0.001). CONCLUSION Treatment with adalimumab for up to 5 years demonstrated sustained benefits in spinal mobility, disease activity, physical function and HRQoL in patients with active AS. Spinal mobility was significantly associated with short- and long-term physical function in these patients. TRIAL REGISTRATION Clinicaltrials.gov; https://clinicaltrials.gov/NCT00085644.
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Affiliation(s)
- Désirée van der Heijde
- Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands, Rheumatology Division, Hôpital Ambroise Paré, AP-HP, University of Versailles-Saint-Quentin-en-Yvelines, Boulogne-Billancourt Cedex, France, Houston Institute for Clinical Research, Houston, TX, Coastal Clinical Research, Inc., Mobile, AL, USA, Department of Rheumatology, Karolinska University Hospital, Huddinge, Sweden, Department of Rheumatology, Nuovo Ospedale S. Stefano, Prato, Italy, Pharmaceutical Development, AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany, Pharmaceutical Development, AbbVie, Data and Statistical Sciences, AbbVie, North Chicago, IL, USA, Department of Gastroenterology, Infectiology and Rheumatology, Charité Universitätsmedizin Berlin, Berlin, Germany and Rheumatology and Internal Medicine, Seattle Rheumatology Associates, Swedish Medical Center, University of Washington School of Medicine, Seattle, WA, USA
| | - Maxime Breban
- Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands, Rheumatology Division, Hôpital Ambroise Paré, AP-HP, University of Versailles-Saint-Quentin-en-Yvelines, Boulogne-Billancourt Cedex, France, Houston Institute for Clinical Research, Houston, TX, Coastal Clinical Research, Inc., Mobile, AL, USA, Department of Rheumatology, Karolinska University Hospital, Huddinge, Sweden, Department of Rheumatology, Nuovo Ospedale S. Stefano, Prato, Italy, Pharmaceutical Development, AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany, Pharmaceutical Development, AbbVie, Data and Statistical Sciences, AbbVie, North Chicago, IL, USA, Department of Gastroenterology, Infectiology and Rheumatology, Charité Universitätsmedizin Berlin, Berlin, Germany and Rheumatology and Internal Medicine, Seattle Rheumatology Associates, Swedish Medical Center, University of Washington School of Medicine, Seattle, WA, USA
| | - Dale Halter
- Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands, Rheumatology Division, Hôpital Ambroise Paré, AP-HP, University of Versailles-Saint-Quentin-en-Yvelines, Boulogne-Billancourt Cedex, France, Houston Institute for Clinical Research, Houston, TX, Coastal Clinical Research, Inc., Mobile, AL, USA, Department of Rheumatology, Karolinska University Hospital, Huddinge, Sweden, Department of Rheumatology, Nuovo Ospedale S. Stefano, Prato, Italy, Pharmaceutical Development, AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany, Pharmaceutical Development, AbbVie, Data and Statistical Sciences, AbbVie, North Chicago, IL, USA, Department of Gastroenterology, Infectiology and Rheumatology, Charité Universitätsmedizin Berlin, Berlin, Germany and Rheumatology and Internal Medicine, Seattle Rheumatology Associates, Swedish Medical Center, University of Washington School of Medicine, Seattle, WA, USA
| | - Gino DiVittorio
- Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands, Rheumatology Division, Hôpital Ambroise Paré, AP-HP, University of Versailles-Saint-Quentin-en-Yvelines, Boulogne-Billancourt Cedex, France, Houston Institute for Clinical Research, Houston, TX, Coastal Clinical Research, Inc., Mobile, AL, USA, Department of Rheumatology, Karolinska University Hospital, Huddinge, Sweden, Department of Rheumatology, Nuovo Ospedale S. Stefano, Prato, Italy, Pharmaceutical Development, AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany, Pharmaceutical Development, AbbVie, Data and Statistical Sciences, AbbVie, North Chicago, IL, USA, Department of Gastroenterology, Infectiology and Rheumatology, Charité Universitätsmedizin Berlin, Berlin, Germany and Rheumatology and Internal Medicine, Seattle Rheumatology Associates, Swedish Medical Center, University of Washington School of Medicine, Seattle, WA, USA
| | - Johan Bratt
- Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands, Rheumatology Division, Hôpital Ambroise Paré, AP-HP, University of Versailles-Saint-Quentin-en-Yvelines, Boulogne-Billancourt Cedex, France, Houston Institute for Clinical Research, Houston, TX, Coastal Clinical Research, Inc., Mobile, AL, USA, Department of Rheumatology, Karolinska University Hospital, Huddinge, Sweden, Department of Rheumatology, Nuovo Ospedale S. Stefano, Prato, Italy, Pharmaceutical Development, AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany, Pharmaceutical Development, AbbVie, Data and Statistical Sciences, AbbVie, North Chicago, IL, USA, Department of Gastroenterology, Infectiology and Rheumatology, Charité Universitätsmedizin Berlin, Berlin, Germany and Rheumatology and Internal Medicine, Seattle Rheumatology Associates, Swedish Medical Center, University of Washington School of Medicine, Seattle, WA, USA
| | - Fabrizio Cantini
- Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands, Rheumatology Division, Hôpital Ambroise Paré, AP-HP, University of Versailles-Saint-Quentin-en-Yvelines, Boulogne-Billancourt Cedex, France, Houston Institute for Clinical Research, Houston, TX, Coastal Clinical Research, Inc., Mobile, AL, USA, Department of Rheumatology, Karolinska University Hospital, Huddinge, Sweden, Department of Rheumatology, Nuovo Ospedale S. Stefano, Prato, Italy, Pharmaceutical Development, AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany, Pharmaceutical Development, AbbVie, Data and Statistical Sciences, AbbVie, North Chicago, IL, USA, Department of Gastroenterology, Infectiology and Rheumatology, Charité Universitätsmedizin Berlin, Berlin, Germany and Rheumatology and Internal Medicine, Seattle Rheumatology Associates, Swedish Medical Center, University of Washington School of Medicine, Seattle, WA, USA
| | - Sonja Kary
- Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands, Rheumatology Division, Hôpital Ambroise Paré, AP-HP, University of Versailles-Saint-Quentin-en-Yvelines, Boulogne-Billancourt Cedex, France, Houston Institute for Clinical Research, Houston, TX, Coastal Clinical Research, Inc., Mobile, AL, USA, Department of Rheumatology, Karolinska University Hospital, Huddinge, Sweden, Department of Rheumatology, Nuovo Ospedale S. Stefano, Prato, Italy, Pharmaceutical Development, AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany, Pharmaceutical Development, AbbVie, Data and Statistical Sciences, AbbVie, North Chicago, IL, USA, Department of Gastroenterology, Infectiology and Rheumatology, Charité Universitätsmedizin Berlin, Berlin, Germany and Rheumatology and Internal Medicine, Seattle Rheumatology Associates, Swedish Medical Center, University of Washington School of Medicine, Seattle, WA, USA
| | - Aileen L Pangan
- Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands, Rheumatology Division, Hôpital Ambroise Paré, AP-HP, University of Versailles-Saint-Quentin-en-Yvelines, Boulogne-Billancourt Cedex, France, Houston Institute for Clinical Research, Houston, TX, Coastal Clinical Research, Inc., Mobile, AL, USA, Department of Rheumatology, Karolinska University Hospital, Huddinge, Sweden, Department of Rheumatology, Nuovo Ospedale S. Stefano, Prato, Italy, Pharmaceutical Development, AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany, Pharmaceutical Development, AbbVie, Data and Statistical Sciences, AbbVie, North Chicago, IL, USA, Department of Gastroenterology, Infectiology and Rheumatology, Charité Universitätsmedizin Berlin, Berlin, Germany and Rheumatology and Internal Medicine, Seattle Rheumatology Associates, Swedish Medical Center, University of Washington School of Medicine, Seattle, WA, USA
| | - Hartmut Kupper
- Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands, Rheumatology Division, Hôpital Ambroise Paré, AP-HP, University of Versailles-Saint-Quentin-en-Yvelines, Boulogne-Billancourt Cedex, France, Houston Institute for Clinical Research, Houston, TX, Coastal Clinical Research, Inc., Mobile, AL, USA, Department of Rheumatology, Karolinska University Hospital, Huddinge, Sweden, Department of Rheumatology, Nuovo Ospedale S. Stefano, Prato, Italy, Pharmaceutical Development, AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany, Pharmaceutical Development, AbbVie, Data and Statistical Sciences, AbbVie, North Chicago, IL, USA, Department of Gastroenterology, Infectiology and Rheumatology, Charité Universitätsmedizin Berlin, Berlin, Germany and Rheumatology and Internal Medicine, Seattle Rheumatology Associates, Swedish Medical Center, University of Washington School of Medicine, Seattle, WA, USA
| | - Suchitrita S Rathmann
- Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands, Rheumatology Division, Hôpital Ambroise Paré, AP-HP, University of Versailles-Saint-Quentin-en-Yvelines, Boulogne-Billancourt Cedex, France, Houston Institute for Clinical Research, Houston, TX, Coastal Clinical Research, Inc., Mobile, AL, USA, Department of Rheumatology, Karolinska University Hospital, Huddinge, Sweden, Department of Rheumatology, Nuovo Ospedale S. Stefano, Prato, Italy, Pharmaceutical Development, AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany, Pharmaceutical Development, AbbVie, Data and Statistical Sciences, AbbVie, North Chicago, IL, USA, Department of Gastroenterology, Infectiology and Rheumatology, Charité Universitätsmedizin Berlin, Berlin, Germany and Rheumatology and Internal Medicine, Seattle Rheumatology Associates, Swedish Medical Center, University of Washington School of Medicine, Seattle, WA, USA
| | - Joachim Sieper
- Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands, Rheumatology Division, Hôpital Ambroise Paré, AP-HP, University of Versailles-Saint-Quentin-en-Yvelines, Boulogne-Billancourt Cedex, France, Houston Institute for Clinical Research, Houston, TX, Coastal Clinical Research, Inc., Mobile, AL, USA, Department of Rheumatology, Karolinska University Hospital, Huddinge, Sweden, Department of Rheumatology, Nuovo Ospedale S. Stefano, Prato, Italy, Pharmaceutical Development, AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany, Pharmaceutical Development, AbbVie, Data and Statistical Sciences, AbbVie, North Chicago, IL, USA, Department of Gastroenterology, Infectiology and Rheumatology, Charité Universitätsmedizin Berlin, Berlin, Germany and Rheumatology and Internal Medicine, Seattle Rheumatology Associates, Swedish Medical Center, University of Washington School of Medicine, Seattle, WA, USA
| | - Phillip J Mease
- Department of Rheumatology, Leiden University Medical Center, Leiden, The Netherlands, Rheumatology Division, Hôpital Ambroise Paré, AP-HP, University of Versailles-Saint-Quentin-en-Yvelines, Boulogne-Billancourt Cedex, France, Houston Institute for Clinical Research, Houston, TX, Coastal Clinical Research, Inc., Mobile, AL, USA, Department of Rheumatology, Karolinska University Hospital, Huddinge, Sweden, Department of Rheumatology, Nuovo Ospedale S. Stefano, Prato, Italy, Pharmaceutical Development, AbbVie Deutschland GmbH & Co. KG, Ludwigshafen, Germany, Pharmaceutical Development, AbbVie, Data and Statistical Sciences, AbbVie, North Chicago, IL, USA, Department of Gastroenterology, Infectiology and Rheumatology, Charité Universitätsmedizin Berlin, Berlin, Germany and Rheumatology and Internal Medicine, Seattle Rheumatology Associates, Swedish Medical Center, University of Washington School of Medicine, Seattle, WA, USA
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Kotsis K, Voulgari PV, Drosos AA, Carvalho AF, Hyphantis T. Health-related quality of life in patients with ankylosing spondylitis: a comprehensive review. Expert Rev Pharmacoecon Outcomes Res 2014; 14:857-72. [PMID: 25193010 DOI: 10.1586/14737167.2014.957679] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
Ankylosing spondylitis (AS) is a complex systemic rheumatological disease which often causes severe disability and impaired quality of life (QoL). We searched the PubMed/MEDLINE electronic database for available literature on QoL and its predictors in patients with AS. Recent evidence indicates that AS patients have poorer QoL compared to the general population, but similar to that of patients with other rheumatological disorders. Disease activity is one of the most powerful predictors of QoL, however latest advances in pharmacological treatment (namely, anti-TNF-α) along with physical exercise can minimize the effects of AS on QoL. Psychological distress symptoms contribute to impaired QoL both directly and indirectly by influencing disease activity. The impact of other psychosocial variables, however, is less studied and more prospective investigations are necessary, which could eventually lead to the development of psychosocial interventions that are personalized to this patient population.
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Affiliation(s)
- Konstantinos Kotsis
- Department of Psychiatry, Division of Medicine, School of Health Sciences, University of Ioannina, Ioannina 45110, Greece
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Kiltz U, Sieper J, Kellner H, Krause D, Rudwaleit M, Chenot JF, Stallmach A, Jaresch S, Braun J. [German Society for Rheumatology S3 guidelines on axial spondyloarthritis including Bechterew's disease and early forms: 8.4 Pharmaceutical therapy, 8.5 Evaluation of therapy success of pharmaceutical measures]. Z Rheumatol 2014; 73 Suppl 2:78-96. [PMID: 25181978 DOI: 10.1007/s00393-014-1443-7] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Affiliation(s)
- U Kiltz
- Deutsche Gesellschaft für Rheumatologie (DGRh), Berlin, Deutschland,
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Song IH, Hermann KG, Haibel H, Althoff CE, Poddubnyy D, Listing J, Weiß A, Buß B, Freundlich B, Lange E, Alten R, Rudwaleit M, Sieper J. Consistently Good Clinical Response in Patients with Early Axial Spondyloarthritis After 3 Years of Continuous Treatment with Etanercept: Longterm Data of the ESTHER Trial. J Rheumatol 2014; 41:2034-40. [DOI: 10.3899/jrheum.140056] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Objective.In patients with early active axial spondyloarthritis (axSpA) with a disease duration of < 5 years, the longterm efficacy of 3 years of continuous etanercept (ETN) treatment was assessed.Methods.In a previously reported ESTHER trial, patients with axSpA were randomized to treatment with ETN (n = 40) versus sulfasalazine (SSZ; n = 36) in the first year. We analyzed the clinical, laboratory, and magnetic resonance imaging (MRI) response in the pooled dataset of patients (study population; n = 61), including patients with ankylosing spondylitis (AS, n = 31) and nonradiographic axSpA (nr-axSpA, n = 30) who were continuously treated with ETN for 3 consecutive years. Data were analyzed using the last observation carried forward and completer analysis.Results.In the entire group of patients in the study population (n = 61), the mean Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) decreased from 5.7 (± 1.3) at baseline to 2.6 (± 2.4) at Year 3. The Ankylosing Spondylitis Disease Activity Score (ASDAS) decreased from 3.4 (± 0.8) to 1.5 (± 1.0). Also, mean values for MRI spine and sacroiliac joint scores showed a significant decrease. Response rates in the nr-axSpA group were similar and at least as good compared to the AS group for all outcome measures. When comparing remission stages, we found that ASDAS inactive disease correlated better with C-reactive protein and MRI remission than with Assessment of SpondyloArthritis international Society partial remission.Conclusion.There was a consistent and sustained clinical response in patients with early axSpA treated with ETN over 3 years. ClinicalTrials.gov registration number NCT00844142.
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Baraliakos X, Braun J. Anti-TNF-α therapy with infliximab in spondyloarthritides. Expert Rev Clin Immunol 2014; 6:9-19. [DOI: 10.1586/eci.09.61] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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Landewé R, Braun J, Deodhar A, Dougados M, Maksymowych WP, Mease PJ, Reveille JD, Rudwaleit M, van der Heijde D, Stach C, Hoepken B, Fichtner A, Coteur G, de Longueville M, Sieper J. Efficacy of certolizumab pegol on signs and symptoms of axial spondyloarthritis including ankylosing spondylitis: 24-week results of a double-blind randomised placebo-controlled Phase 3 study. Ann Rheum Dis 2014; 73:39-47. [PMID: 24013647 PMCID: PMC3888598 DOI: 10.1136/annrheumdis-2013-204231] [Citation(s) in RCA: 355] [Impact Index Per Article: 32.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2013] [Revised: 08/19/2013] [Accepted: 08/20/2013] [Indexed: 12/14/2022]
Abstract
OBJECTIVES To evaluate the efficacy and safety of certolizumab pegol (CZP) after 24 weeks in RAPID-axSpA (NCT01087762), an ongoing Phase 3 trial in patients with axial spondyloarthritis (axSpA), including patients with ankylosing spondylitis (AS) and non-radiographic axSpA (nr-axSpA). METHODS Patients with active axSpA were randomised 1:1:1 to placebo, CZP 200 mg every 2 weeks (Q2W) or CZP 400 mg every 4 weeks (Q4W). In total 325 patients were randomised. Primary endpoint was ASAS20 (Assessment of SpondyloArthritis international Society 20) response at week 12. Secondary outcomes included change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), and Bath Ankylosing Spondylitis Metrology Index (BASMI) linear. RESULTS Baseline disease activity was similar between AS and nr-axSpA. At week 12, ASAS20 response rates were significantly higher in CZP 200 mg Q2W and CZP 400 mg Q4W arms versus placebo (57.7 and 63.6 vs 38.3, p≤0.004). At week 24, combined CZP arms showed significant (p<0.001) differences in change from baseline versus placebo in BASFI (-2.28 vs -0.40), BASDAI (-3.05 vs -1.05), and BASMI (-0.52 vs -0.07). Improvements were observed as early as week 1. Similar improvements were reported with CZP versus placebo in both AS and nr-axSpA subpopulations. Adverse events were reported in 70.4% vs 62.6%, and serious adverse events in 4.7% vs 4.7% of All CZP versus placebo groups. No deaths or malignancies were reported. CONCLUSIONS CZP rapidly reduced the signs and symptoms of axSpA, with no new safety signals observed compared to the safety profile of CZP in RA. Similar improvements were observed across CZP dosing regimens, and in AS and nr-axSpA patients.
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Affiliation(s)
- R Landewé
- Academic Medical Center Amsterdam & Atrium Medical Center Heerlen, , Amsterdam, The Netherlands
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Upadhyaya SK. Antibodies to Tumor Necrosis Factors in the Treatment of Rheumatoid Arthritis and Spondyloarthritis: The Basic Science, Clinical Science and Unmet Needs; Results from a Single Center. ACTA ACUST UNITED AC 2014. [DOI: 10.4236/ojra.2014.42013] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022]
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McArthur M, Birt L, Goodacre L. A Narrative Literature Review of the Impact of Anti-TNFα Treatment on the Occupational Performance of People with Rheumatoid Arthritis or Ankylosing Spondylitis. Br J Occup Ther 2013. [DOI: 10.4276/030802213x13807217284260] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/31/2023]
Abstract
Introduction: Anti-TNFα treatment has revolutionised the disease pathway for some people with rheumatoid arthritis and ankylosing spondylitis, although physiological improvements do not always readily translate into re-engagement in occupational activities. This review explores the evidence base for the impact of anti-TNFα on occupational performance. Method: Literature was searched from 2000–11. A four-stage process resulted in the review of 19 articles. The Weight of Evidence framework was used to assess quality and relevance to the review question. Findings: People on anti-TNFα treatment experience increased engagement in functional, psychological and social domains. Most studies focused on employment issues, with conflicting evidence about how well anti-TNFα protected against work disability and very limited evidence that anti-TNFα enabled return to paid work. The increase in productivity was to the detriment of other occupational domains, with resulting occupational imbalance. Conclusion: The assumption that clinical improvement is relatively trouble free is incorrect, as some people on anti-TNFα treatment continue to experience difficulties in all occupational domains, particularly work. People on anti-TNFα treatment do not routinely have access to occupational therapy services. Further research needs to explore the nuanced experiences of treatment and the role of occupational therapy in maximising the treatment potential of anti-TNFα.
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Affiliation(s)
- Margaret McArthur
- Honorary Fellow, University of East Anglia, School of Rehabilitation Sciences, Norwich
| | - Linda Birt
- Research Associate, University of East Anglia, School of Rehabilitation Sciences, Norwich
| | - Lynne Goodacre
- Research Fellow, Lancaster University, School of Medicine and Health Sciences, Lancaster
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Plasencia C, Pascual-Salcedo D, García-Carazo S, Lojo L, Nuño L, Villalba A, Peiteado D, Arribas F, Díez J, López-Casla MT, Martín-Mola E, Balsa A. The immunogenicity to the first anti-TNF therapy determines the outcome of switching to a second anti-TNF therapy in spondyloarthritis patients. Arthritis Res Ther 2013; 15:R79. [PMID: 23890223 PMCID: PMC3978754 DOI: 10.1186/ar4258] [Citation(s) in RCA: 56] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2013] [Accepted: 07/26/2013] [Indexed: 01/09/2023] Open
Abstract
Introduction Anti-TNF drugs have proven to be effective against spondyloarthritis (SpA), although 30% of patients fail to respond or experience adverse events leading to treatment discontinuation. In rheumatoid arthritis, the presence of anti-drug antibodies (ADA) against the first TNF inhibitor influences the outcome after switching. Our aim was to assess whether the response to a second anti-TNF drug is related to the previous development of ADA to the first anti-TNF drug SpA patients. Methods Forty-two SpA patients began a second anti-TNF drug after failing to respond to the first anti-TNF therapy. Clinical activity was assessed by the Ankylosing Spondylitis Disease Activity Score (ASDAS) at baseline (at the beginning of the first and second anti-TNF therapy) and at 6 months after switching. The drug and ADA levels were measured by ELISA before each administration. Results All patients were treated with anti-TNF drugs and mainly due to inefficacy were switched to a second anti-TNF drug. Eleven of 42 (26.2%) developed ADA during the first biologic treatment. At baseline, no differences in ASDAS were found in patients with or without ADA to the first anti-TNF drug (3.52 ± 1.03 without ADA vs. 3.14 ± 0.95 with ADA, p = 0.399) and to the second anti-TNF drug (3.36 ± 0.94 without ADA vs. 3.09 ± 0.91 with ADA, p = 0.466). At 6 months after switching, patients with previous ADA had lower disease activity (1.62 ± 0.93 with ADA vs. 2.79 ± 1.01 without ADA, p = 0.002) and most patients without ADA had high disease activity state by the ASDAS (25 out of 31 (80.6%) without ADA vs. 3 out of 11 (27.3%) with ADA, p = 0.002). Conclusions In SpA the failure to respond to the first anti-TNF drug due to the presence of ADA predicts a better clinical response to a second anti-TNF drug.
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Moll M, Kuemmerle-Deschner JB. Inflammasome and cytokine blocking strategies in autoinflammatory disorders. Clin Immunol 2013; 147:242-75. [DOI: 10.1016/j.clim.2013.04.008] [Citation(s) in RCA: 57] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2012] [Revised: 04/07/2013] [Accepted: 04/12/2013] [Indexed: 12/20/2022]
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Ehrenfeld M. Spondyloarthropathies. Best Pract Res Clin Rheumatol 2013; 26:135-45. [PMID: 22424199 DOI: 10.1016/j.berh.2012.01.002] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/01/2011] [Revised: 12/20/2011] [Accepted: 01/04/2012] [Indexed: 12/17/2022]
Abstract
Spondyloarthropathies (SpA) are a group of common inflammatory rheumatic disorders characterised by axial and or peripheral arthritis, associated with enthesitis, dactylitis and potential extra-articular manifestations such as uveitis and skin rash. The diseases, which comprise the group, share a common genetic predisposition, the HLA-B27 gene; however, this association varies markedly among the various SpAs and among different ethnic groups. Environmental factors seem to be triggering the diseases in the genetically predisposed individuals. The radiographic hallmark of the group is sacroiliitis, which when present is of help in the diagnosis. Various sets of diagnostic and classification criteria were developed over the years including the European Spondyloarthropathy Study Group (ESSG) criteria which were until recently the most widely used. The new Assessment in SpondyloArthritis international Society (ASAS) international working group has recently proposed a new set of diagnostic criteria that would enable identification of SpA before structural changes develop in the spine. Magnetic resonance imaging (MRI) changes have now been included in the new classification criteria of early axial SpA and are now considered as a major tool in the diagnosis. Until recently, there were no real disease-modifying anti-rheumatic drugs which were able to halt the disease progression. Over the past decade, tumour necrosis factor (TNF)-alfa-blocking agents have been extensively investigated and became the mainstream of therapy providing the patients an effective treatment option.
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Affiliation(s)
- Michael Ehrenfeld
- Zabludowicz Center for Autoimmune Diseases, Chaim Sheba Medical Center, Tel-Hashomer 52621, Israel.
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Cytokine levels in the serum of healthy subjects. Mediators Inflamm 2013; 2013:434010. [PMID: 23533306 PMCID: PMC3606775 DOI: 10.1155/2013/434010] [Citation(s) in RCA: 245] [Impact Index Per Article: 20.4] [Reference Citation Analysis] [Abstract] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2012] [Accepted: 02/16/2013] [Indexed: 01/21/2023] Open
Abstract
Growing knowledge about the cytokine network response has led to a better comprehension of mechanisms of pathologies and to the development of new treatments with biological drugs, able to block specific molecules of the immune response. Indeed, when the cytokine production is deregulated, diseases often occur. The understanding of the physiological mechanism of the cytokine network would be useful to better comprehend pathological conditions. Moreover, since the immune system and response change their properties with development, differences in patients' age should be taken into account, both in physiological and in pathological conditions. In this study, we analyzed the profile of 48 cytokines and chemokines in the serum of healthy subjects, comparing adults (≥18 years) with young children and children (1–6 and 7–17 years). We found that a certain number of cytokines were not being produced in healthy subjects; others showed a constant serum level amongst the groups. Certain cytokines exhibited a downward or an upward trend with increasing age. The remaining cytokines were up- or downregulated in the group of the children with respect to the other groups. In conclusion, we drew some kinds of guidelines about the physiological production of cytokines and chemokines, underling the difference caused by aging.
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Baughman RP, Meyer KC, Nathanson I, Angel L, Bhorade SM, Chan KM, Culver D, Harrod CG, Hayney MS, Highland KB, Limper AH, Patrick H, Strange C, Whelan T. Monitoring of nonsteroidal immunosuppressive drugs in patients with lung disease and lung transplant recipients: American College of Chest Physicians evidence-based clinical practice guidelines. Chest 2012; 142:e1S-e111S. [PMID: 23131960 PMCID: PMC3610695 DOI: 10.1378/chest.12-1044] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 03/06/2012] [Indexed: 01/19/2023] Open
Abstract
OBJECTIVES Immunosuppressive pharmacologic agents prescribed to patients with diffuse interstitial and inflammatory lung disease and lung transplant recipients are associated with potential risks for adverse reactions. Strategies for minimizing such risks include administering these drugs according to established, safe protocols; monitoring to detect manifestations of toxicity; and patient education. Hence, an evidence-based guideline for physicians can improve safety and optimize the likelihood of a successful outcome. To maximize the likelihood that these agents will be used safely, the American College of Chest Physicians established a committee to examine the clinical evidence for the administration and monitoring of immunosuppressive drugs (with the exception of corticosteroids) to identify associated toxicities associated with each drug and appropriate protocols for monitoring these agents. METHODS Committee members developed and refined a series of questions about toxicities of immunosuppressives and current approaches to administration and monitoring. A systematic review was carried out by the American College of Chest Physicians. Committee members were supplied with this information and created this evidence-based guideline. CONCLUSIONS It is hoped that these guidelines will improve patient safety when immunosuppressive drugs are given to lung transplant recipients and to patients with diffuse interstitial lung disease.
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Affiliation(s)
| | - Keith C Meyer
- University of Wisconsin School of Medicine and Public Health, Madison, WI
| | | | - Luis Angel
- University of Texas Health Sciences, San Antonio, TX
| | | | - Kevin M Chan
- University of Michigan Health Systems, Ann Arbor, MI
| | | | | | - Mary S Hayney
- University of Wisconsin School of Pharmacy, Madison, WI
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Li ZH, Zhang Y, Wang J, Shi ZJ. Etanercept in the treatment of ankylosing spondylitis: a meta-analysis of randomized, double-blind, placebo-controlled clinical trials, and the comparison of the Caucasian and Chinese population. EUROPEAN JOURNAL OF ORTHOPAEDIC SURGERY AND TRAUMATOLOGY 2012; 23:497-506. [PMID: 23412168 DOI: 10.1007/s00590-012-1035-7] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/06/2012] [Accepted: 06/18/2012] [Indexed: 12/17/2022]
Abstract
BACKGROUND AND PURPOSE Ankylosing spondylitis (AS) is a kind of rheumatic disease, leading to pain, fatigue, stiffness, and functional impairment, which seriously affects the quality of life. Etanercept, a fully human recombinant protein, has been applied for the treatment of AS. However, there has not been a systematic analysis for its efficacy and safety. METHODS This meta-analysis of fourteen randomized, double-blind, placebo-controlled clinical trials with 1,570 participants was performed to investigate the efficacy and safety of etanercept, by means of calculating the overall relative risk, and to compare the different responses between the Caucasian population and the Chinese population. RESULTS Generally, there was sufficient evidence to prove that etanercept has its advantages in both disease activity controlling and symptoms relieving, especially for axial joints compared with peripheric joints, without higher incidence of serious adverse events. INTERPRETATION Our preliminary analysis provided that the Caucasian population has better response to etanercept treatment, with more treatment-emergent adverse events. Further specially designed clinical trials need to be performed to investigate the different responses between axial and peripheric joints, also between different races.
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Affiliation(s)
- Zhi-han Li
- Department of Orthopaedic Surgery, Nanfang Hospital, Guangzhou, Guangdong Province, China
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Wang YXJ, Griffith JF, Deng M, Li TK, Tam LS, Lee VWY, Lee KKC, Li EK. Vertebral body corner oedema vs gadolinium enhancement as biomarkers of active spinal inflammation in ankylosing spondylitis. Br J Radiol 2012; 85:e702-8. [PMID: 22595499 DOI: 10.1259/bjr/29661937] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
OBJECTIVE To investigate the relative performance of T(2) weighted short tau inversion-recovery (STIR) and fat-suppressed T(1) weighted gadolinium contrast-enhanced sequences in depicting active inflammatory lesions in ankylosing spondylitis (AS). METHODS Whole-spine MRI was performed on 32 patients with AS, who participated in a clinical trial of infliximab treatment, by STIR and contrast-enhanced sequences at baseline and after 30 weeks. The AS spine MRI-activity (ASspiMRI-a) scoring method was used. The images from these two imaging techniques were evaluated separately by two independent readers. RESULTS For the pre-treatment lesion status, the intraclass correlation coefficients comparing STIR readings and contrast-enhanced readings were 0.69±0.23 for Reader 1 and 0.65±0.21 for Reader 2. At baseline, the mean ASspiMRI-a score was 15.4% and 17.7% higher for contrast-enhanced images than for STIR images for Reader 1 and Reader 2, respectively. After infliximab treatment, Reader 1 rated an ASspiMRI-a score reduction of 50.8±33.6% and 25.3±35.3% for STIR images and contrast-enhanced images, respectively, whereas Reader 2 rated an ASspiMRI-a score reduction of 42.4±50.4% and 32.9±35.6% for STIR images and contrast-enhanced images, respectively. CONCLUSION While both contrast-enhanced and STIR sequences showed sensitivity to change over a short period of time after infliximab treatment, these two sequences may reflect different disease mechanisms.
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Affiliation(s)
- Y-X J Wang
- Department of Imaging and Interventional Radiology, The Chinese University of Hong Kong, Prince of Wales Hospital,Shatin, Hong Kong, China.
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Sieper J, van der Heijde D, Dougados M, Brown LS, Lavie F, Pangan AL. Early response to adalimumab predicts long-term remission through 5 years of treatment in patients with ankylosing spondylitis. Ann Rheum Dis 2012; 71:700-6. [PMID: 22128084 PMCID: PMC3329233 DOI: 10.1136/annrheumdis-2011-200358] [Citation(s) in RCA: 63] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/24/2011] [Accepted: 10/09/2011] [Indexed: 02/06/2023]
Abstract
OBJECTIVES To describe the efficacy and safety through 5 years of adalimumab treatment in patients with ankylosing spondylitis (AS), and to identify predictors of remission. METHODS Patients with active AS were followed up to 5 years during a 24-week randomised, controlled period, followed by an open-label extension. Disease activity and clinical improvement were evaluated by Assessment in Spondyloarthritis International Society (ASAS) responses, Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and Ankylosing Spondylitis Disease Activity Score (ASDAS). Kaplan-Meier was used to identify patients with sustained ASAS partial remission (PR) or ASDAS inactive disease (ID) for three or more consecutive visits spanning ≥ 6 months. Logistic regression was used to identify factors associated with remission. Explanatory variables included baseline demographic and disease characteristics and week 12 responses. RESULTS Of the 311 patients who received at least one dose of adalimumab, 202 (65%) completed the 5-year study. Among 125 patients who received 5 years of adalimumab, 70%, 77%, 51% and 61% achieved ASAS40, BASDAI 50, ASAS PR and ASDAS ID, respectively. Of 311 adalimumab-treated patients, 45% and 55% achieved sustained ASAS PR and ASDAS ID at any time during study participation. The strongest predictor of remission at years 1 and 5 and of sustained remission was achieving remission at 12 weeks of treatment; baseline characteristics showed weaker associations. Adverse events were comparable with previous reports on adalimumab safety. CONCLUSIONS In patients with active AS, the efficacy and safety of adalimumab were maintained through 5 years with about half of the patients experiencing sustained remission at any time during the study. Early achievement of remission was the best predictor of long-term and sustained remission.
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Affiliation(s)
- Joachim Sieper
- University Clinic Benjamin Franklin, Medical Department I, Rheumatology, PO Box, Berlin 12200, Germany.
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