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1
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Tukek NB, Bakkaloglu OK, Sen G, Hatemi İ, Celik AF, Erzin YZ. The effects of biologics on ulcerative colitis-related colectomy rate: results of a 22-year study. Scand J Gastroenterol 2025; 60:548-557. [PMID: 40302309 DOI: 10.1080/00365521.2025.2497954] [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: 01/02/2025] [Revised: 02/25/2025] [Accepted: 04/22/2025] [Indexed: 05/02/2025]
Abstract
BACKGROUND To assess the impact of the biological era on colectomy rates in ulcerative colitis (UC) patients and identify factors associated with the necessity for colectomy in a large cohort from Eastern Europe. METHODS A retrospective cohort study was conducted on UC patients followed at a tertiary care center covering 1999 to 2021. Patients who underwent colectomy due to disease activity were compared to those who did not. Factors related to colectomy and the influence of the biological era were analyzed. RESULTS Among 1197 patients with a median follow-up of 3.3 years, 18% received biological agents and 5.3% underwent colectomy due to disease activity. The colectomy rate was lower in the biological era compared to the pre-biological era (2% vs. 12%; p < 0.001). Independent predictors of colectomy included steroid dependency, steroid resistance, lack of mucosal remission, and elevated CRP levels. Patients who achieved and maintained mucosal remission and had CRP levels below 3 mg/L had a significantly lower risk of colectomy. CONCLUSIONS The biological era has significantly reduced colectomy rates in UC patients. Achieving mucosal remission and maintaining low CRP levels are essential for preventing colectomy and improving long-term outcomes.
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Affiliation(s)
- Nur Beyza Tukek
- Clinic of Internal Medicine, Tekirdag Dr Ismail Fehmi Cumalioglu City Hospital, Tekirdag, Turkey
| | - Oguz Kagan Bakkaloglu
- Division of Gastroenterology, Department of Internal Medicine, Kosuyolu High Specialization Research and Education Hospital, Istanbul, Turkey
| | - Gozde Sen
- Clinic of Internal Medicine, Istanbul Bahcelievler State Hospital, Istanbul, Turkey
| | - İbrahim Hatemi
- Division of Gastroenterology, Department of Internal Medicine, Cerrahpasa Medical Faculty, Istanbul University, Cerrahpasa, Istanbul, Turkey
| | - Aykut Ferhat Celik
- Division of Gastroenterology, Department of Internal Medicine, Cerrahpasa Medical Faculty, Istanbul University, Cerrahpasa, Istanbul, Turkey
| | - Yusuf Ziya Erzin
- Division of Gastroenterology, Department of Internal Medicine, Cerrahpasa Medical Faculty, Istanbul University, Cerrahpasa, Istanbul, Turkey
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2
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Kawczak P, Feszak IJ, Bączek T. Abatacept, Golimumab, and Sarilumab as Selected Bio-Originator Disease-Modifying Antirheumatic Drugs with Diverse Mechanisms of Action in Their Current Use in Treatment. J Clin Med 2025; 14:2107. [PMID: 40142915 PMCID: PMC11943273 DOI: 10.3390/jcm14062107] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2025] [Revised: 03/13/2025] [Accepted: 03/17/2025] [Indexed: 03/28/2025] Open
Abstract
Background/Objectives: Arthritis encompasses a range of joint-related conditions, including osteoarthritis and rheumatoid arthritis, along with inflammatory diseases such as gout and lupus. This research study explores the underlying causes, challenges, and treatment options for arthritis, aiming to enhance the effectiveness of therapies. Methods: This research study evaluated current treatment strategies and examined the effectiveness of selected biological disease-modifying antirheumatic drugs (bDMARDs), i.e., abatacept, golimumab, and sarilumab, with a focus on emerging drug classes and their distinct mechanisms of action. Results: Biologic DMARDs like abatacept, golimumab, and sarilumab offer hopeful treatment alternatives for patients who fail to respond to conventional therapies. However, individual outcomes differ because of the disease's complexity and the influence of accompanying health conditions. Conclusions: Treating arthritis continues to be challenging due to its numerous underlying causes and the varied ways in which patients respond to treatment. Although biologics and targeted therapies have brought progress, additional research is needed to identify new treatment targets and enhance patient results.
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Affiliation(s)
- Piotr Kawczak
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University of Gdańsk, 80-416 Gdańsk, Poland;
| | - Igor Jarosław Feszak
- Institute of Health Sciences, Pomeranian University in Słupsk, 76-200 Słupsk, Poland;
| | - Tomasz Bączek
- Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Medical University of Gdańsk, 80-416 Gdańsk, Poland;
- Department of Nursing and Medical Rescue, Institute of Health Sciences, Pomeranian University in Słupsk, 76-200 Słupsk, Poland
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3
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Okazaki R, Hirata I, Ikegami H, Rokutanda R, Funakoshi R. Case report: Ulcerative colitis-related spondyloarthritis treated with golimumab until 27 weeks of gestation. Obstet Med 2024:1753495X241297559. [PMID: 39605871 PMCID: PMC11590078 DOI: 10.1177/1753495x241297559] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2024] [Accepted: 10/17/2024] [Indexed: 11/29/2024] Open
Abstract
Although tumor necrosis factor inhibitors are recommended for preventing flare-ups in pregnant women with ulcerative colitis (UC), studies on golimumab use during pregnancy are scant. Herein, we present a 39-year-old woman with UC and spondyloarthritis. The patient preferred treatment with a long dosing interval that minimally affects the working life of the patient. Golimumab, considering its long dosing interval, was prescribed after discussion with the patient, physician and pharmacists. Clinical remission was achieved during pregnancy, and the patient delivered a healthy baby. The vaccines were administered according to the vaccine schedule: during the first year after birth, there were neither infections caused by live vaccines nor diseases that the administered vaccines are meant to prevent. Overall, this case suggests that golimumab treatment during pregnancy may be compatible; however, further evaluations, including drug-level analysis, are needed.
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Affiliation(s)
- Ryuichi Okazaki
- Department of Pharmacy, Kameda General Hospital, Kamogawa Shi, Chiba Ken, Japan
| | - Ikkou Hirata
- Department of Pharmacy, Kameda General Hospital, Kamogawa Shi, Chiba Ken, Japan
| | | | - Ryou Rokutanda
- Department of Rheumatology, Kameda General Hospital, Kamogawa Shi, Chiba Ken, Japan
| | - Ryohkan Funakoshi
- Department of Pharmacy, Kameda General Hospital, Kamogawa Shi, Chiba Ken, Japan
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4
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Qiu W, Wang Z, Liu Q, Du Q, Zeng X, Wu Z, Pan D, Zhang X, Tu M. Structure and regulatory mechanisms of food-derived peptides in inflammatory bowel disease: A review. Food Sci Nutr 2024; 12:6055-6069. [PMID: 39554349 PMCID: PMC11561845 DOI: 10.1002/fsn3.4228] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/10/2024] [Revised: 05/01/2024] [Accepted: 05/02/2024] [Indexed: 11/19/2024] Open
Abstract
The number of patients with inflammatory bowel disease (IBD) is increasing worldwide. Since IBD is a chronic disease that seriously affects patients' life quality, preventing and alleviating IBD with natural and less side effect substances has become a research hotspot. Food-derived bioactive peptides have been an attractive research focus due to their high efficiency and low toxicity. This paper comprehensively summarizes food-derived peptides with intestinal health effects, focusing on peptide sequences with IBD-regulatory effects and emphasizing the effects of their structure and physicochemical properties such as peptide length, amino acid composition, and net charge on their function. We also analyzed its regulatory mechanisms, mainly in 5 aspects: modulating the intestinal microbiota, decreasing intestinal epithelial permeability, increasing antioxidant ability, regulating the expression of inflammatory cytokines, and targeting signaling pathways. This review will help establish novel, efficient screening methods for IBD-regulatory peptides and contribute to further research and discovery of them.
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Affiliation(s)
- Wenpei Qiu
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro‐ProductsNingbo UniversityNingboZhejiangChina
- Zhejiang‐Malaysia Joint Research Laboratory for Agricultural Product Processing and Nutrition, College of Food Science and EngineeringNingbo UniversityNingboChina
| | - Zhicheng Wang
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro‐ProductsNingbo UniversityNingboZhejiangChina
- Zhejiang‐Malaysia Joint Research Laboratory for Agricultural Product Processing and Nutrition, College of Food Science and EngineeringNingbo UniversityNingboChina
| | - Qirui Liu
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro‐ProductsNingbo UniversityNingboZhejiangChina
- Zhejiang‐Malaysia Joint Research Laboratory for Agricultural Product Processing and Nutrition, College of Food Science and EngineeringNingbo UniversityNingboChina
| | - Qiwei Du
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro‐ProductsNingbo UniversityNingboZhejiangChina
- Zhejiang‐Malaysia Joint Research Laboratory for Agricultural Product Processing and Nutrition, College of Food Science and EngineeringNingbo UniversityNingboChina
| | - Xiaoqun Zeng
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro‐ProductsNingbo UniversityNingboZhejiangChina
- Zhejiang‐Malaysia Joint Research Laboratory for Agricultural Product Processing and Nutrition, College of Food Science and EngineeringNingbo UniversityNingboChina
| | - Zhen Wu
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro‐ProductsNingbo UniversityNingboZhejiangChina
- Zhejiang‐Malaysia Joint Research Laboratory for Agricultural Product Processing and Nutrition, College of Food Science and EngineeringNingbo UniversityNingboChina
| | - Daodong Pan
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro‐ProductsNingbo UniversityNingboZhejiangChina
- Zhejiang‐Malaysia Joint Research Laboratory for Agricultural Product Processing and Nutrition, College of Food Science and EngineeringNingbo UniversityNingboChina
| | | | - Maolin Tu
- State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro‐ProductsNingbo UniversityNingboZhejiangChina
- Zhejiang‐Malaysia Joint Research Laboratory for Agricultural Product Processing and Nutrition, College of Food Science and EngineeringNingbo UniversityNingboChina
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5
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Sakib S, Zou S. Attenuation of Chronic Inflammation in Intestinal Organoids with Graphene Oxide-Mediated Tumor Necrosis Factor-α_Small Interfering RNA Delivery. LANGMUIR : THE ACS JOURNAL OF SURFACES AND COLLOIDS 2024. [PMID: 38325360 PMCID: PMC10883062 DOI: 10.1021/acs.langmuir.3c02741] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/09/2024]
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the gastrointestinal tract with a complex and multifactorial etiology, making it challenging to treat. While recent advances in immunomodulatory biologics, such as antitumor necrosis factor-α (TNF-α) antibodies, have shown moderate success, systemic administration of antibody therapeutics may lead to several adverse effects, including the risk of autoimmune disorders due to systemic cytokine depletion. Transient RNA interference using exogenous short interfering RNA (siRNA) to regulate target gene expression at the transcript level offers an alternative to systemic immunomodulation. However, siRNAs are susceptible to premature degradation and have poor cellular uptake. Graphene oxide (GO) nanoparticles have been shown to be effective nanocarriers for biologics due to their reduced cytotoxicity and enhanced bioavailability. In this study, we evaluate the therapeutic efficacy of GO mediated TNF-α_siRNA using in vitro models of chronic inflammation generated by treating murine small intestines (enteroids) and large intestines (colonoids) with inflammatory agents IL-1β, TNF-α, and LPS. The organotypic mouse enteroids and colonoids developed an inflammatory phenotype similar to that of IBD, characterized by impaired epithelial homeostasis and an increased production of inflammatory cytokines such as TNF-α, IL-1β, and IL-6. We assessed siRNA delivery to these inflamed organoids using three different GO formulations. Out of the three, small-sized GO with polymer and dendrimer modifications (smGO) demonstrated the highest transfection efficiency, which led to the downregulation of inflammatory cytokines, indicating an attenuation of the inflammatory phenotype. Moreover, the transfection efficiency and inflammation-ameliorating effects could be further enhanced by increasing the TNF-α_siRNA/smGO ratio from 1:1 to 3:1. Overall, the results of this study demonstrate that ex vivo organoids with disease-specific phenotypes are invaluable models for assessing the therapeutic potential of nanocarrier-mediated drug and biologic delivery systems.
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Affiliation(s)
- Sadman Sakib
- Metrology Research Centre, National Research Council of Canada, 100 Sussex Drive, Ottawa, ONK1A 0R6, Canada
| | - Shan Zou
- Metrology Research Centre, National Research Council of Canada, 100 Sussex Drive, Ottawa, ONK1A 0R6, Canada
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6
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Sharma P, Joshi RV, Pritchard R, Xu K, Eicher MA. Therapeutic Antibodies in Medicine. Molecules 2023; 28:6438. [PMID: 37764213 PMCID: PMC10535987 DOI: 10.3390/molecules28186438] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2023] [Revised: 08/05/2023] [Accepted: 08/28/2023] [Indexed: 09/29/2023] Open
Abstract
Antibody engineering has developed into a wide-reaching field, impacting a multitude of industries, most notably healthcare and diagnostics. The seminal work on developing the first monoclonal antibody four decades ago has witnessed exponential growth in the last 10-15 years, where regulators have approved monoclonal antibodies as therapeutics and for several diagnostic applications, including the remarkable attention it garnered during the pandemic. In recent years, antibodies have become the fastest-growing class of biological drugs approved for the treatment of a wide range of diseases, from cancer to autoimmune conditions. This review discusses the field of therapeutic antibodies as it stands today. It summarizes and outlines the clinical relevance and application of therapeutic antibodies in treating a landscape of diseases in different disciplines of medicine. It discusses the nomenclature, various approaches to antibody therapies, and the evolution of antibody therapeutics. It also discusses the risk profile and adverse immune reactions associated with the antibodies and sheds light on future applications and perspectives in antibody drug discovery.
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Affiliation(s)
- Prerna Sharma
- Geisinger Commonwealth School of Medicine, Scranton, PA 18509, USA
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7
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Gold S, Cohen L. Anti-TNF Therapies Other Than Infliximab for the Treatment of Pediatric Inflammatory Bowel Disease. PEDIATRIC INFLAMMATORY BOWEL DISEASE 2023:423-443. [DOI: 10.1007/978-3-031-14744-9_32] [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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8
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Goll R, Moe ØK, Johnsen KM, Meyer R, Friestad J, Gundersen MD, Kileng H, Johnsen K, Florholmen JR. Pharmacodynamic mechanisms behind a refractory state in inflammatory bowel disease. BMC Gastroenterol 2022; 22:464. [DOI: 10.1186/s12876-022-02559-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/31/2022] [Accepted: 10/29/2022] [Indexed: 11/18/2022] Open
Abstract
Abstract
Background and aims
Biological therapy for inflammatory bowel disease is efficient in many cases but not all. The underlying molecular mechanisms behind non-response to biological therapy in inflammatory bowel disease are poorly described. Therefore, we aimed to characterize the mucosal cytokine transcript profile in non-immunogenic, non-responder patients with adequate trough level.
Material and methods
Patients with ulcerative colitis (UC) (n = 21) and Crohn’s disease (CD) (n = 12) with non-response to biological therapy (anti-tumor necrosis factor (TNF) or vedolizumab) were included. Reference groups were A: untreated patients with UC or CD at debut of disease who had severe 1-year outcome, B: patients with UC or CD treated to endoscopic remission with biological agents, and C: healthy normal controls. Mucosal transcripts of TNF, interleukin (IL)17 and IL23 were measured by reverse transcription real-time quantitative polymerase chain reaction.
Results
Of the non-responders, 2 out of 12 CD and 1 out of 21 UC patients needed surgery during follow-up. Of the remaining non-responding patients, 8 out of 10 CD and 12 out of 20 UC patients switched biologic treatment. The remaining 2 CD and 8 UC patients continued treatment with the same biological agent with the addition of steroids, immunomodulators (AZA/MTX) and /or local steroids/5ASA. Twelve (8 UC/4 CD) out of 20 IBD patients were still non-responders after changing biological therapy to either anti-TNF (2), vedolizumab (9) or ustekinumab (1).
The transcripts of IL17, IL23 and TNF were significantly upregulated in the non-response group compared to normal controls and patients in remission. In UC, 24% of the non-responders had normal mucosal TNF transcript indicating a non-TNF mediated inflammation. No obvious differences in gene expression were observed between primary and secondary non-responders, nor between anti-TNF and vedolizumab non-responders.
Conclusions
Mucosal transcripts of IL17 and IL23 are highly associated with non-response to biological therapy, whereas some UC patients may also have a non-TNF mediated inflammatory pathway.
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9
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Oral Nanomedicines for siRNA Delivery to Treat Inflammatory Bowel Disease. Pharmaceutics 2022; 14:pharmaceutics14091969. [PMID: 36145716 PMCID: PMC9503894 DOI: 10.3390/pharmaceutics14091969] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2022] [Revised: 09/09/2022] [Accepted: 09/14/2022] [Indexed: 11/16/2022] Open
Abstract
RNA interference (RNAi) therapies have significant potential for the treatment of inflammatory bowel diseases (IBD). Although administering small interfering RNA (siRNA) via an oral route is desirable, various hurdles including physicochemical, mucus, and cellular uptake barriers of the gastrointestinal tract (GIT) impede both the delivery of siRNA to the target site and the action of siRNA drugs at the target site. In this review, we first discuss various physicochemical and biological barriers in the GI tract. Furthermore, we present recent strategies and the progress of oral siRNA delivery strategies to treat IBD. Finally, we consider the challenges faced in the use of these strategies and future directions of oral siRNA delivery strategies.
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10
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Huldani H, Margiana R, Ahmad F, Opulencia MJC, Ansari MJ, Bokov DO, Abdullaeva NN, Siahmansouri H. Immunotherapy of inflammatory bowel disease (IBD) through mesenchymal stem cells. Int Immunopharmacol 2022; 107:108698. [PMID: 35306284 DOI: 10.1016/j.intimp.2022.108698] [Citation(s) in RCA: 35] [Impact Index Per Article: 11.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Revised: 03/02/2022] [Accepted: 03/10/2022] [Indexed: 02/07/2023]
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11
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Risto A, Abdalla M, Myrelid P. Staging Pouch Surgery in Ulcerative Colitis in the Biological Era. Clin Colon Rectal Surg 2022; 35:58-65. [PMID: 35069031 PMCID: PMC8763463 DOI: 10.1055/s-0041-1740039] [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: 01/19/2023]
Abstract
Restorative proctocolectomy, or ileal pouch anal anastomosis, is considered the standard treatment for intractable ulcerative colitis. When the pelvic pouch was first introduced in 1978, a two-stage procedure with proctocolectomy, construction of the pelvic pouch, and a diverting loop with subsequent closure were suggested. Over the decades that the pelvic pouch has been around, some principal technical issues have been addressed to improve the method. In more recent days the laparoscopic approach has been additionally introduced. During the same time-period the medical arsenal has developed far more with the increasing use of immune modulators and the introduction of biologicals. Staging of restorative proctocolectomy with a pelvic pouch refers to how many sessions, or stages, the procedure should be divided into. The main goal with restorative proctocolectomy is a safe operation with optimal short- and long-term function. In this paper we aim to review the present knowledge and views on staging of the pouch procedure in ulcerative colitis, especially with consideration to the treatment with biologicals.
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Affiliation(s)
- Anton Risto
- Department of Surgery, Linköping University Hospital and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Maie Abdalla
- Department of Surgery, Vrinnevi Hospital, Norrköping and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden
| | - Pär Myrelid
- Department of Surgery, Linköping University Hospital and Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden,Address for correspondence Pär Myrelid, MD, PhD Department of Surgery, Linköping University HospitalSE-581 85 LinköpingSweden
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12
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Roy A, Geetha RV, Magesh A, Vijayaraghavan R, Ravichandran V. Autoinjector - A smart device for emergency cum personal therapy. Saudi Pharm J 2021; 29:1205-1215. [PMID: 34703373 PMCID: PMC8523323 DOI: 10.1016/j.jsps.2021.09.004] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2021] [Accepted: 09/11/2021] [Indexed: 12/18/2022] Open
Abstract
Autoinjectors are self-injectable devices; they are important class of medical devices which can deliver drugs through subcutaneous or intramuscular route. They enclose prefilled syringes or cartridges which are driven by a spring system. The major benefits of this device are easy self-administration, improved patient compliance, reduced anxiety, and dosage accuracy. Immediate treatment during emergency conditions such as anaphylaxis, migraine, and status epilepticus or for chronic conditions like psoriasis, diabetes, multiple sclerosis, and rheumatoid arthritis, Reformulation of first-generation biologics, technical advancements, innovative designs, patient compliance, overwhelming interest for self-administration all these made entry of more and more autoinjectors into use. In this review, intensive efforts have been made for exploring the different types of currently available autoinjectors for the management of emergency and chronic diseases.
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Affiliation(s)
- Anitha Roy
- Department of Pharmacology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India
| | - Royapuram Veeraragavan Geetha
- Department of Microbiology, Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India
| | - Anitha Magesh
- Department of Research and Development, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India
| | - Rajagopalan Vijayaraghavan
- Department of Research and Development, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India
| | - Veerasamy Ravichandran
- Pharmaceutical Chemistry Unit, Faculty of Pharmacy, AIMST University, Semeling-08100, Bedong, Malaysia.,Centre of Excellence for Biomaterials Engineering, AIMST University, Semeling-08100, Bedong, Malaysia.,Saveetha Dental College and Hospitals, Saveetha Institute of Medical and Technical Sciences, Chennai, Tamil Nadu, India
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13
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Lubrano E, Luchetti MM, Benfaremo D, Mauro D, Ciccia F, Perrotta FM. Inflammatory bowel disease manifestations in spondyloarthritis: considerations for the clinician. Expert Rev Clin Immunol 2021; 17:1199-1209. [PMID: 34622735 DOI: 10.1080/1744666x.2021.1991315] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Spondyloarthropathies (SpA) are a group of inflammatory arthritis that can involve the spine and/or peripheral joints. Extra-articular manifestations, such as inflammatory bowel disease (IBD), are frequently observed within the clinical manifestations of SpA and are part of the SpA classification criteria. Evidence of IBD is observed in about 6-7% of SpA patients, and a silent, microscopic gut inflammation, could be present in up to 50% of patients. From a pathogenetic point of view, dysregulated microbiome and migration of T lymphocytes and other cells from gut to the joint ('gut-joint' axis) has been recognized, in the context of a common genetic background. AREAS COVERED The aim of this paper is to narratively review the recent evidences on the epidemiology, classification, clinical findings, pathogenesis, diagnosis, and treatment of IBD in patients with SpA and to provide advices for both rheumatologist and gastroenterologist in the management of IBD in SpA. EXPERT OPINION IBD manifestations in SpA frequently increase the burden of the disease and represent a clinical challenge, especially for the diagnosis, assessment, and treatment of patients affected by those conditions. New treatment strategies targeting both articular and intestinal manifestations are now available and may lead to a better outcome.
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Affiliation(s)
- Ennio Lubrano
- Dipartimento Di Medicina E Scienze Della Salute "Vincenzo Tiberio", Università Degli Studi Del Molise, Campobasso, Italy
| | - Michele Maria Luchetti
- Dipartimento Scienze Cliniche E Molecolari, Università Politecnica Delle Marche & Polo Didattico Ospedaliero "Umberto I-g.m. Lancisi-G.Salesi ", Ancona, Italy
| | - Devis Benfaremo
- Dipartimento Scienze Cliniche E Molecolari, Università Politecnica Delle Marche & Polo Didattico Ospedaliero "Umberto I-g.m. Lancisi-G.Salesi ", Ancona, Italy
| | - Daniele Mauro
- Dipartimento Di Medicina Di Precisione, Università Degli Studi Della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Francesco Ciccia
- Dipartimento Di Medicina Di Precisione, Università Degli Studi Della Campania "Luigi Vanvitelli", Napoli, Italy
| | - Fabio Massimo Perrotta
- Dipartimento Di Medicina E Scienze Della Salute "Vincenzo Tiberio", Università Degli Studi Del Molise, Campobasso, Italy
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14
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Hashash JG, Fadel CGA, Rimmani HH, Sharara AI. Biologic monotherapy versus combination therapy with immunomodulators in the induction and maintenance of remission of Crohn's disease and ulcerative colitis. Ann Gastroenterol 2021; 34:612-624. [PMID: 34475731 PMCID: PMC8375659 DOI: 10.20524/aog.2021.0645] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2021] [Accepted: 03/12/2021] [Indexed: 12/19/2022] Open
Abstract
Despite current guidelines, the optimal treatment of patients with inflammatory bowel disease (IBD) remains challenging. The available medications are not without risk and there is not a single correct treatment regimen for every patient. Personalizing treatment and selecting the most appropriate therapy is crucial for optimal response, remission, quality of life, and healthcare utilization. Biologics, especially anti-tumor necrosis factor-α medications, are widely used in the induction and maintenance of disease remission in patients with IBD. Similarly, immunomodulators, including thiopurines and methotrexate, are traditionally popular for the maintenance of remission. In this manuscript, we review the use of biologic monotherapy vs. combination therapy with immunomodulators for the treatment of ulcerative colitis and Crohn's disease. We examine overall remission, immunogenicity and adverse effects, mainly serious infections and malignancy, in an effort to help guide treatment decisions and weigh the risks and benefits of biologic monotherapy vs. combination therapy.
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Affiliation(s)
- Jana G. Hashash
- Division of Gastroenterology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut (Jana G. Hashash, Hussein H. Rimmani, Ala I. Sharara)
| | - Carla G. Abou Fadel
- Division of Gastroenterology, Bellevue Medical Center, Mansourieh (Carla G. Abou Fadel), Lebanon
| | - Hussein H. Rimmani
- Division of Gastroenterology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut (Jana G. Hashash, Hussein H. Rimmani, Ala I. Sharara)
| | - Ala I. Sharara
- Division of Gastroenterology, Department of Internal Medicine, American University of Beirut Medical Center, Beirut (Jana G. Hashash, Hussein H. Rimmani, Ala I. Sharara)
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Di Ruscio M, Variola A, Vernia F, Lunardi G, Castelli P, Bocus P, Geccherle A. Role of Ulcerative Colitis Endoscopic Index of Severity (UCEIS) versus Mayo Endoscopic Subscore (MES) in Predicting Patients' Response to Biological Therapy and the Need for Colectomy. Digestion 2021; 102:534-545. [PMID: 32739919 DOI: 10.1159/000509512] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/03/2020] [Accepted: 06/16/2020] [Indexed: 02/04/2023]
Abstract
BACKGROUND The main goal in the treatment of ulcerative colitis (UC) is to achieve mucosal healing. Despite being unvalidated, the most widely used scoring system is the Mayo endoscopic subscore (MES). However, the recently established and validated Ulcerative Colitis Endoscopic Index of Severity (UCEIS) represents an interesting alternative method in assessing endoscopic disease activity. OBJECTIVE Due to a lack of reliable prognostic factors, the aim of this study was to investigate the diagnostic accuracy of the UCEIS and the MES, in predicting response to biological therapy and the need for colectomy. METHODS We conducted a retrospective, uncontrolled, single-center study on UC patients with endoscopically active disease even with concomitant conventional and/or biological therapy, who had already started or had been changed a biological treatment. RESULTS Sixty-one UC patients were enrolled. At baseline, 71% were naive to biological therapies and 41% had an extensive colitis. At control time (median time of 11.5 months), MES and UCEIS scores significantly decreased from those at baseline (from 2.6 to 1.8 and 5 to 3.2, respectively, p < 0.001). UCEIS, but not MES, was found to be significantly associated with unresponsiveness to therapy (p = 0.040). Moreover, when UCEIS was ≥7, all patients underwent colectomy after a median time of 5 months (p < 0.001). CONCLUSION UCEIS may be superior to MES because of its accuracy and predictive role. Therefore, UCEIS should be considered for use in daily clinical practice.
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Affiliation(s)
- Mirko Di Ruscio
- IBD Unit, IRCCS Sacro Cuore Don Calabria, Negrar di Valpolicella, Italy,
| | - Angela Variola
- IBD Unit, IRCCS Sacro Cuore Don Calabria, Negrar di Valpolicella, Italy
| | - Filippo Vernia
- Gastroenterology Unit, Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, Italy
| | - Gianluigi Lunardi
- Medical Analysis Laboratory, IRCCS Sacro Cuore Don Calabria, Negrar di Valpolicella, Italy
| | - Paola Castelli
- Department of Pathology, IRCCS Sacro Cuore Don Calabria, Negrar di Valpolicella, Italy
| | - Paolo Bocus
- Gastroenterology Unit, IRCCS Sacro Cuore Don Calabria, Negrar di Valpolicella, Italy
| | - Andrea Geccherle
- IBD Unit, IRCCS Sacro Cuore Don Calabria, Negrar di Valpolicella, Italy
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Melendez-Gonzalez MDM, Hamad J, Sayed C. Golimumab for the Treatment of Hidradenitis Suppurativa in Patients with Previous TNF-α Treatment Failure. J Invest Dermatol 2021; 141:2975-2979. [PMID: 34097922 DOI: 10.1016/j.jid.2021.04.026] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/02/2020] [Revised: 04/06/2021] [Accepted: 04/08/2021] [Indexed: 10/21/2022]
Affiliation(s)
| | - Judy Hamad
- UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
| | - Christopher Sayed
- Department of Dermatology, UNC School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
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Melo AT, Campanilho-Marques R, Fonseca JE. Golimumab (anti-TNF monoclonal antibody): where we stand today. Hum Vaccin Immunother 2021; 17:1586-1598. [PMID: 33369527 PMCID: PMC8115761 DOI: 10.1080/21645515.2020.1836919] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2020] [Revised: 09/17/2020] [Accepted: 10/09/2020] [Indexed: 01/07/2023] Open
Abstract
Tumor necrosis factor (TNF) is a pro-inflammatory cytokine and its overexpression has been implicated in the pathophysiology of several chronic immune-mediated inflammatory diseases. Biological therapies, like TNF inhibitors, have been revolutionizing the course of these disorders. Golimumab is a transgenic anti-TNF monoclonal antibody that acts primarily by targeting and neutralizing TNF, thus preventing inflammation. It is approved for the treatment of Rheumatoid Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis, Nonradiographic axial Spondyloarthritis, Juvenile Idiopathic Arthritis, and Ulcerative Colitis. Clinical trials are also being conducted in other conditions. This review charts the clinical development of golimumab and outlines the data that support its potential use across several Immune-mediated inflammatory diseases.
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Affiliation(s)
- Ana Teresa Melo
- 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
| | - Raquel Campanilho-Marques
- 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
| | - João Eurico Fonseca
- 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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Niu W, Chen X, Xu R, Dong H, Yang F, Wang Y, Zhang Z, Ju J. Polysaccharides from natural resources exhibit great potential in the treatment of ulcerative colitis: A review. Carbohydr Polym 2020; 254:117189. [PMID: 33357839 DOI: 10.1016/j.carbpol.2020.117189] [Citation(s) in RCA: 137] [Impact Index Per Article: 27.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2020] [Revised: 09/29/2020] [Accepted: 09/30/2020] [Indexed: 02/08/2023]
Abstract
The incidence of ulcerative colitis (UC) is high. Despite the availability of various therapeutic agents for the treatment of UC, the routine treatment has limitations and serious side effects. Therefore, a new drug that safely and effectively treats UC is urgently needed. Polysaccharides from natural resources have recently become a hot topic of study for their therapeutic effects on UC. These effects are associated with the regulation of inflammatory cytokines, intestinal flora, and immune system and protection of the intestinal mucosa. This review focuses on the recent advances of polysaccharides from natural resources in the treatment of UC. The mechanisms and practicability of polysaccharides, including pectin, guar gum, rhamnogalacturonan, chitosan, fructan, psyllium, glycosaminoglycan, algal polysaccharides, polysaccharides from fungi and traditional Chinese medicine, and polysaccharide derivatives, are discussed in detail. The good efficacy and safety of polysaccharides make them promising drugs for treating UC.
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Affiliation(s)
- Wei Niu
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, PR China; Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, PR China
| | - Xiaoqing Chen
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, PR China; Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, PR China
| | - Ruling Xu
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, PR China; Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, PR China; Anhui University of Chinese Medicine, Hefei, PR China
| | - Huimin Dong
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, PR China; Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, PR China
| | - Fuyan Yang
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, PR China; Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, PR China; Anhui University of Chinese Medicine, Hefei, PR China
| | - Yun Wang
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, PR China; Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, PR China
| | - Zhenhai Zhang
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, PR China; Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, PR China.
| | - Jianming Ju
- Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, PR China; Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, PR China.
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Mishra R, Dhawan P, Srivastava AS, Singh AB. Inflammatory bowel disease: Therapeutic limitations and prospective of the stem cell therapy. World J Stem Cells 2020; 12:1050-1066. [PMID: 33178391 PMCID: PMC7596447 DOI: 10.4252/wjsc.v12.i10.1050] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2020] [Revised: 06/02/2020] [Accepted: 09/22/2020] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD), consisting primarily of ulcerative colitis and Crohn’s disease, is a group of debilitating auto-immune disorders, which also increases the risk of colitis-associated cancer. However, due to the chronic nature of the disease and inconsistent treatment outcomes of current anti-IBD drugs (e.g., approximately 30% non-responders to anti-TNFα agents), and related serious side effects, about half of all IBD patients (in millions) turn to alternative treatment options. In this regard, mucosal healing is gaining acceptance as a measure of disease activity in IBD patients as recent studies have correlated the success of mucosal healing with improved prognosis. However, despite the increasing clinical realization of the significance of the concept of mucosal healing, its regulation and means of therapeutic targeting remain largely unclear. Here, stem-cell therapy, which uses hematopoietic stem cells or mesenchymal stem cells, remains a promising option. Stem cells are the pluripotent cells with ability to differentiate into the epithelial and/or immune-modulatory cells. The over-reaching concept is that the stem cells can migrate to the damaged areas of the intestine to provide curative help in the mucosal healing process. Moreover, by differentiating into the mature intestinal epithelial cells, the stem cells also help in restoring the barrier integrity of the intestinal lining and hence prevent the immunomodulatory induction, the root cause of the IBD. In this article, we elaborate upon the current status of the clinical management of IBD and potential role of the stem cell therapy in improving IBD therapy and patient’s quality of life.
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Affiliation(s)
- Rangnath Mishra
- Global Institute of Stem Cell Therapy and Research, San Diego, CA 92122, United States
| | - Punita Dhawan
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68118, United States
- Fred and Pamela Buffett Cancer Center, Omaha, NE 68118, United States
- VA Nebraska-Western Iowa Health Care System, Omaha, NE 68118, United States
| | - Anand S Srivastava
- Global Institute of Stem Cell Therapy and Research, San Diego, CA 92122, United States
| | - Amar B Singh
- Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE 68118, United States
- Fred and Pamela Buffett Cancer Center, Omaha, NE 68118, United States
- VA Nebraska-Western Iowa Health Care System, Omaha, NE 68118, United States
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20
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Cordeiro N, Freitas RHCN, Fraga CAM, Fernandes PD. Therapeutic Effects of Anti-Inflammatory N-Acylhydrazones in the Resolution of Experimental Colitis. J Pharmacol Exp Ther 2020; 374:420-427. [PMID: 32546529 DOI: 10.1124/jpet.120.000074] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2020] [Accepted: 06/04/2020] [Indexed: 01/15/2023] Open
Abstract
Inflammatory bowel diseases are caused by inflammation of the gastrointestinal tract, which may or may not have a specific cause or pathogen. They affect millions of people around the world and there are still few effective treatments. The aim of this work is to investigate the anti-inflammatory effect of the IKK-β inhibitor LASSBio-1524 and its three analogs, LASSBio-1760, LASSBio-1763, and LASSBio-1764, on mediator production and expression of inflammatory enzymes using experimental animal models of intestinal inflammatory diseases. Colitis was performed using two different models, which mimic Crohn disease (induced by dinitrobenzene acid) and ulcerative colitis (induced by sodium dextran sulfate) in mice. In both models, a therapeutic protocol with a daily dose of 1, 3, or 30 μmol/kg was performed. LASSBio-1524 and its three analogs reduced the secretion of tumor necrosis factor-α, IL-1β, IL-6, IL-12, and IFN-γ and increased secretion of IL-10, protecting gastrointestinal homeostasis. All compounds reduced macro- and microscopic colonic damage caused by experimental colitis and p38 mitogen-activated protein kinase expression in the colon, as well as leukocytosis and anemia resulting from the disease. Our data may suggest LASSBio-1524 and its analogs (LASSBio-1760, LASSBio-1763, and LASSBio-1764) as promising candidates for new prototypes designed to treat inflammatory bowel diseases. SIGNIFICANCE STATEMENT: Three new N-acylhydrazones were synthetized as analogs of LASSBio-1524. All new substances were evaluated in dextran sulfate- and dinitrobenzene acid-induced colitis, with LASSBio-1760, LASSBio-1762, and LASSBio-1763 presenting a significant effect in both models of colitis without toxic effects. The new substances could be considered as a new prototype for the development of new anti-inflammatory treatments of colitis.
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Affiliation(s)
- Natália Cordeiro
- Universidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Laboratório de Farmacologia da Dor e da Inflamação, Rio de Janeiro, Brasil (N.d.M.C., P.D.F.); Universidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Programa de Pós-graduação em Farmacologia e Química Medicinal, Rio de Janeiro, Brasil (N.d.M.C., P.D.F., C.A.M.F.); and Universidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Laboratório de Avaliação e Síntese de Substâncias Bioativas (LASSBio), Rio de Janeiro, Brasil (R.H.C.N.F., C.A.M.F.)
| | - Rosana Helena Coimbra Nogueira Freitas
- Universidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Laboratório de Farmacologia da Dor e da Inflamação, Rio de Janeiro, Brasil (N.d.M.C., P.D.F.); Universidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Programa de Pós-graduação em Farmacologia e Química Medicinal, Rio de Janeiro, Brasil (N.d.M.C., P.D.F., C.A.M.F.); and Universidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Laboratório de Avaliação e Síntese de Substâncias Bioativas (LASSBio), Rio de Janeiro, Brasil (R.H.C.N.F., C.A.M.F.)
| | - Carlos Alberto Manssour Fraga
- Universidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Laboratório de Farmacologia da Dor e da Inflamação, Rio de Janeiro, Brasil (N.d.M.C., P.D.F.); Universidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Programa de Pós-graduação em Farmacologia e Química Medicinal, Rio de Janeiro, Brasil (N.d.M.C., P.D.F., C.A.M.F.); and Universidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Laboratório de Avaliação e Síntese de Substâncias Bioativas (LASSBio), Rio de Janeiro, Brasil (R.H.C.N.F., C.A.M.F.)
| | - Patricia Dias Fernandes
- Universidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Laboratório de Farmacologia da Dor e da Inflamação, Rio de Janeiro, Brasil (N.d.M.C., P.D.F.); Universidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Programa de Pós-graduação em Farmacologia e Química Medicinal, Rio de Janeiro, Brasil (N.d.M.C., P.D.F., C.A.M.F.); and Universidade Federal do Rio de Janeiro, Instituto de Ciências Biomédicas, Laboratório de Avaliação e Síntese de Substâncias Bioativas (LASSBio), Rio de Janeiro, Brasil (R.H.C.N.F., C.A.M.F.)
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Yeshi K, Ruscher R, Hunter L, Daly NL, Loukas A, Wangchuk P. Revisiting Inflammatory Bowel Disease: Pathology, Treatments, Challenges and Emerging Therapeutics Including Drug Leads from Natural Products. J Clin Med 2020; 9:E1273. [PMID: 32354192 PMCID: PMC7288008 DOI: 10.3390/jcm9051273] [Citation(s) in RCA: 92] [Impact Index Per Article: 18.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/14/2020] [Revised: 04/18/2020] [Accepted: 04/20/2020] [Indexed: 02/07/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic and life-long disease characterized by gastrointestinal tract inflammation. It is caused by the interplay of the host's genetic predisposition and immune responses, and various environmental factors. Despite many treatment options, there is no cure for IBD. The increasing incidence and prevalence of IBD and lack of effective long-term treatment options have resulted in a substantial economic burden to the healthcare system worldwide. Biologics targeting inflammatory cytokines initiated a shift from symptomatic control towards objective treatment goals such as mucosal healing. There are seven monoclonal antibody therapies excluding their biosimilars approved by the US Food and Drug Administration for induction and maintenance of clinical remission in IBD. Adverse side effects associated with almost all currently available drugs, especially biologics, is the main challenge in IBD management. Natural products have significant potential as therapeutic agents with an increasing role in health care. Given that natural products display great structural diversity and are relatively easy to modify chemically, they represent ideal scaffolds upon which to generate novel therapeutics. This review focuses on the pathology, currently available treatment options for IBD and associated challenges, and the roles played by natural products in health care. It discusses these natural products within the current biodiscovery research agenda, including the applications of drug discovery techniques and the search for next-generation drugs to treat a plethora of inflammatory diseases, with a major focus on IBD.
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Affiliation(s)
- Karma Yeshi
- Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns QLD 4878, Australia
| | - Roland Ruscher
- Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns QLD 4878, Australia
| | - Luke Hunter
- School of Chemistry, University of New South Wales (UNSW), Sydney NSW 2052, Australia
| | - Norelle L. Daly
- Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns QLD 4878, Australia
| | - Alex Loukas
- Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns QLD 4878, Australia
| | - Phurpa Wangchuk
- Centre for Molecular Therapeutics, Australian Institute of Tropical Health and Medicine, James Cook University, Cairns QLD 4878, Australia
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Romeo AC, Ventimiglia M, Dipasquale V, Orlando A, Citrano M, Pellegrino S, Accomando S, Cottone M, Romano C. Effectiveness and safety of biologics in pediatric inflammatory boweldisease: Real-life data from the Sicilian Network. Clin Res Hepatol Gastroenterol 2020; 44:223-229. [PMID: 31204314 DOI: 10.1016/j.clinre.2019.05.008] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/12/2019] [Revised: 05/07/2019] [Accepted: 05/09/2019] [Indexed: 02/07/2023]
Abstract
BACKGROUND Biological therapies have modified the disease course of pediatric inflammatory bowel disease (IBD) and are routinely used in clinical practice. Our observational study aims to evaluate effectiveness and safety of biologics in IBD. METHOD Clinical benefit and safety data of 93 children with IBD, receiving biologics (Infliximab - IFX, Adalimumab - ADA, Golimumab - GOL) from January 2013 to December 2017, were extracted from the cohort of the Sicilian Network of IBD. RESULTS Among 87 children aged 7-17 years (63 Crohn's disease [CD], 24 Ulcerative colitis [UC]), 101 out of 108 biologic treatments were considered. Evaluation of 74 biologic treatments in CD patients at 26, 52, 104 weeks showed clinical benefit rates of 84.2%, 93.3%, 66.7% with IFX (n= 38) and 88.9%, 84.4%, 65.2% with ADA (n= 36). Biologic treatments (n=27) evaluated in the UC group at 26, 52, 104 weeks, led to clinical benefit rates of 85.7%, 83.3%, 50% in IFX subgroup (n=21) and 40%, 50%, 33% in the ADA subgroup (n=5), respectively. One patient treated with GOL showed 100% clinical benefit at 26 and 52 weeks. Overall adverse events (AEs) rate was 9.25%. Six younger children, <6 years, receiving 8 treatments (4 ADA, 4 IFX) presented a clinical remission rate of 75% at 12 weeks and 25% at 52 weeks. AEs rate was 25% in this group. CONCLUSION Our data show that biologic therapy in children, even at a younger age, is effective in allowing long-term remission with a good safety profile.
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Affiliation(s)
- Anna Claudia Romeo
- Pediatric Gastroenterology and Cystic Fibrosis Unit, Department of Human Pathology in Adulthood and Childhood "G. Barresi", University of Messina, Via Consolare Valeria 1, 98124 Messina, Italy
| | - Marco Ventimiglia
- Pediatric Gastroenterology and Cystic Fibrosis Unit, Department of Human Pathology in Adulthood and Childhood "G. Barresi", University of Messina, Via Consolare Valeria 1, 98124 Messina, Italy
| | - Valeria Dipasquale
- Pediatric Gastroenterology and Cystic Fibrosis Unit, Department of Human Pathology in Adulthood and Childhood "G. Barresi", University of Messina, Via Consolare Valeria 1, 98124 Messina, Italy
| | - Ambrogio Orlando
- Pediatric Gastroenterology and Cystic Fibrosis Unit, Department of Human Pathology in Adulthood and Childhood "G. Barresi", University of Messina, Via Consolare Valeria 1, 98124 Messina, Italy
| | - Michele Citrano
- Pediatric Gastroenterology and Cystic Fibrosis Unit, Department of Human Pathology in Adulthood and Childhood "G. Barresi", University of Messina, Via Consolare Valeria 1, 98124 Messina, Italy
| | - Salvatore Pellegrino
- Pediatric Gastroenterology and Cystic Fibrosis Unit, Department of Human Pathology in Adulthood and Childhood "G. Barresi", University of Messina, Via Consolare Valeria 1, 98124 Messina, Italy
| | - Salvatore Accomando
- Pediatric Gastroenterology and Cystic Fibrosis Unit, Department of Human Pathology in Adulthood and Childhood "G. Barresi", University of Messina, Via Consolare Valeria 1, 98124 Messina, Italy
| | - Mario Cottone
- Pediatric Gastroenterology and Cystic Fibrosis Unit, Department of Human Pathology in Adulthood and Childhood "G. Barresi", University of Messina, Via Consolare Valeria 1, 98124 Messina, Italy
| | - Claudio Romano
- Pediatric Gastroenterology and Cystic Fibrosis Unit, Department of Human Pathology in Adulthood and Childhood "G. Barresi", University of Messina, Via Consolare Valeria 1, 98124 Messina, Italy.
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Ibáñez Vodnizza SE, De La Fuente MPP, Parra Cancino EC. Approach to the Patient with Axial Spondyloarthritis and Suspected Inflammatory Bowel Disease. Rheum Dis Clin North Am 2020; 46:275-286. [PMID: 32340701 DOI: 10.1016/j.rdc.2020.01.004] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/25/2022]
Abstract
To adequately and efficiently evaluate patients with gastrointestinal symptoms in the context of axial spondyloarthritis can be difficult, considering that many of these patients suffer from chronic pain, present high inflammatory parameters, and use drugs with possible gastrointestinal adverse effects. In addition, the immunosuppressive treatments that these patients can receive make it necessary to always consider infections within the differential diagnoses of inflammatory bowel disease. In this article, we propose a practical approach to patients diagnosed with axial spondyloarthritis and suspected inflammatory bowel disease.
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Affiliation(s)
- Sebastián Eduardo Ibáñez Vodnizza
- Rheumatology Department, Clínica Alemana de Santiago, Chile; Rheumatology Department, Padre Hurtado Hospital, Santiago, Chile; Medicine Faculty Clínica Alemana de Santiago, Universidad del Desarrollo, Santiago, Chile.
| | - María Paz Poblete De La Fuente
- Medicine Faculty Clínica Alemana de Santiago, Universidad del Desarrollo, Santiago, Chile; Internal Medicine Department, Padre Hurtado Hospital, Secretaría de medicina interna, 4° piso, Esperanza 2150, San Ramón, Santiago 8860000, Chile
| | - Elisa Catalina Parra Cancino
- Medicine Faculty Clínica Alemana de Santiago, Universidad del Desarrollo, Santiago, Chile; Gastroenterology Department, Clínica Alemana de Santiago, Chile; Gastroenterology Department, Padre Hurtado Hospital, Secretaría de medicina interna, 4° piso, Esperanza 2150, San Ramón, Santiago 8860000, Chile
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Chevalier R. siRNA Targeting and Treatment of Gastrointestinal Diseases. Clin Transl Sci 2019; 12:573-585. [PMID: 31309709 PMCID: PMC6853152 DOI: 10.1111/cts.12668] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2019] [Accepted: 06/10/2019] [Indexed: 12/15/2022] Open
Abstract
RNA interference via small interfering RNA (siRNA) offers opportunities to precisely target genes that contribute to gastrointestinal (GI) pathologies, such as inflammatory bowel disease, celiac, and esophageal scarring. Delivering the siRNA to the GI tract proves challenging as the harsh environment of the intestines degrades the siRNA before it can reach its target or blocks its entry into its site of action in the cytoplasm. Additionally, the GI tract is large and disease is often localized to a specific site. This review discusses polymer and lipid‐based delivery systems for protection and targeting of siRNA therapies to the GI tract to treat local disease.
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Affiliation(s)
- Rachel Chevalier
- Children's Mercy Kansas City, Kansas City, Missouri, USA.,University of Missouri-Kansas City School of Medicine, Kansas City, Missouri, USA
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25
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Retnakumar SV, Muller S. Pharmacological Autophagy Regulators as Therapeutic Agents for Inflammatory Bowel Diseases. Trends Mol Med 2019; 25:516-537. [PMID: 30952481 DOI: 10.1016/j.molmed.2019.03.002] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2019] [Revised: 03/03/2019] [Accepted: 03/06/2019] [Indexed: 12/12/2022]
Abstract
The arsenal of effective molecules to treat patients with chronic inflammatory bowel diseases (IBDs) remains limited. These remitting-relapsing diseases have become a global health issue and new therapeutic strategies are eagerly awaited to regulate the course of these disorders. Since the association between autophagy-related gene polymorphism and an increased risk of Crohn's disease (CD) has been discovered, a new domain of investigation has emerged, focused on the intracellular degradation system, with the objective of generating new medicines that are safer and more targeted. This review summarizes the drugs administered to IBD patients and describes recently emerged therapeutic agents. We compile evidence on the contribution of autophagy to IBD pathogenesis, give an overview of pharmacological autophagy regulators in animal models of colitis, and propose novel therapeutic avenues based on autophagy components.
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Affiliation(s)
- Sruthi Vijaya Retnakumar
- CNRS-University of Strasbourg, Biotechnology and Cell signaling, Institut de Science et d'ingénierie Supramoléculaire, 67000 Strasbourg, France
| | - Sylviane Muller
- CNRS-University of Strasbourg, Biotechnology and Cell signaling, Institut de Science et d'ingénierie Supramoléculaire, 67000 Strasbourg, France; University of Strasbourg Institute for Advanced Study, 67000 Strasbourg, France.
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Falloon K, Lazarev M. A Primer on IBD: Phenotypes, Diagnosis, Treatment, and Clinical Challenges. MOLECULAR GENETICS OF INFLAMMATORY BOWEL DISEASE 2019:3-24. [DOI: 10.1007/978-3-030-28703-0_1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Probert CS, Sebastian S, Gaya DR, Hamlin PJ, Gillespie G, Rose A, Tate H, Wheeler C, Irving PM. Golimumab induction and maintenance for moderate to severe ulcerative colitis: results from GO-COLITIS (Golimumab: a Phase 4, UK, open label, single arm study on its utilization and impact in ulcerative Colitis). BMJ Open Gastroenterol 2018; 5:e000212. [PMID: 30002864 PMCID: PMC6038835 DOI: 10.1136/bmjgast-2018-000212] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2018] [Revised: 05/16/2018] [Accepted: 05/25/2018] [Indexed: 01/14/2023] Open
Abstract
OBJECTIVE GO-COLITIS aimed to measure the effectiveness of subcutaneous golimumab in tumour necrosis factor-α antagonist-naive patients with moderate to severe ulcerative colitis (UC) despite conventional treatment. DESIGN GO-COLITIS was an open label, single arm, phase 4 study with a pragmatic design which reflected UK clinical practice. Adult patients were eligible if diagnosed with UC ≥3 months, partial Mayo score (PMS) 4-9. Patients received subcutaneous golimumab induction (200 mg initially and 100 mg at week 2) followed at week 6 by 50 mg or 100 mg (depending on weight) every 4 weeks until week 54 with a 12-week follow-up. Efficacy was measured by PMS at baseline, week 6, 30, 54 and 66. Health-related quality of life (HRQoL; Inflammatory Bowel Disease Questionnaire (IBDQ) and EuroQol Group 5 Dimensions Health Questionnaire (EQ-5D)) was assessed at baseline, week 6 and week 54. All safety adverse events (AEs) were recorded. RESULTS 207 patients were enrolled and 205 received golimumab (full analysis set (FAS)205). At week 6, 68.8% (95% CI 62.0% to 75.1%) and 38.5% (95% CI 31.8% to 45.6%) of patients were in response and remission, respectively, using PMS. At the end of the induction phase, 140/141 patients in clinical response continued into the maintenance phase (Maintenance FAS). Sustained clinical response through week 54 was achieved in 51/205 (24.9%) of the FAS205 population and 51/140 (36.4%) of the Maintenance FAS population. Statistically significant improvements from baseline to week 6 were observed for the IBDQ total score and for each IBDQ domain score (bowel symptoms, emotional function, systemic symptoms and social function), as well as the EQ-5D index score and associated visual analogue scale score (p<0.0001). Improvement of HRQoL was sustained through week 54. Serious AEs leading to treatment discontinuation occurred in 8.8% of patients. CONCLUSION In this study measuring patient-reported outcomes in patients with moderate to severe UC, golimumab induced and maintained response as measured by PMS and significantly improved quality of life measures. TRIAL REGISTRATION NUMBER NCT02092285; 2013-004583-56.
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Affiliation(s)
| | - Shaji Sebastian
- IBD Unit, Hull and East Yorkshire Hospitals NHS Trust Hull, Hull, Kingston upon Hull, UK
| | - Daniel R Gaya
- Gastroenterology Unit, Glasgow Royal Infirmary, Glasgow, UK
| | - P John Hamlin
- Department of Gastroenterology, Leeds Teaching Hospitals NHS Trust, Leeds, UK
| | | | | | - Helen Tate
- New House Farm, Purton End, Saffron Walden, UK
| | | | - Peter M Irving
- Department of Gastroenterology, Guy's and St. Thomas' NHS Foundation Trust, London, UK
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Rawla P, Sunkara T, Raj JP. Role of biologics and biosimilars in inflammatory bowel disease: current trends and future perspectives. J Inflamm Res 2018; 11:215-226. [PMID: 29844695 PMCID: PMC5961645 DOI: 10.2147/jir.s165330] [Citation(s) in RCA: 95] [Impact Index Per Article: 13.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD) is an idiopathic chronic inflammatory disease of the gastrointestinal system. The spectrum is of predominantly two types, namely, ulcerative colitis and Crohn’s disease. The incidence of IBD has been increasing steadily since 1990, and so the number of agents used in their treatment. Biologics that are derived partly or completely from living biological sources such as animals and humans have become widely available, which provide therapeutic benefits to the IBD patients. Currently, monoclonal antibodies against tumor necrosis factor-alpha (infliximab, adalimumab, certolizumab, and golimumab), integrins (vedolizumab and natalizumab), and interleukin (IL)-12 and IL-23 antagonists (ustekinumab) are approved for use in IBD. Biosimilars of infliximab and adalimumab are also available for the treatment of IBD. This review summarizes the clinical pharmacology, studies leading to their approval, overall indications and their use in IBD, usage in pregnancy and lactation, and the adverse effects of these agents. This review also summarizes the recent advances and future perspectives specific to biologics and biosimilars in IBD.
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Affiliation(s)
- Prashanth Rawla
- Department of Internal Medicine, Memorial Hospital of Martinsville and Henry County, Martinsville, VA
| | - Tagore Sunkara
- Division of Gastroenterology and Hepatology, The Brooklyn Hospital Center, Clinical Affiliate of The Mount Sinai Hospital, New York, NY, USA
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