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Nielsen OH, Hammerhøj A, Ainsworth MA, Gubatan J, D'Haens G. Immunogenicity of Therapeutic Antibodies Used for Inflammatory Bowel Disease: Treatment and Clinical Considerations. Drugs 2025; 85:67-85. [PMID: 39532820 DOI: 10.1007/s40265-024-02115-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 10/15/2024] [Indexed: 11/16/2024]
Abstract
The introduction of tumor necrosis factor inhibitors has led to a paradigm shift in the management of inflammatory bowel disease (IBD). The subsequent introduction of both anti-integrins and cytokine blockers has since expanded the biologic armamentarium. However, immunogenicity, defined as the production of anti-drug antibodies (ADAs) to the prescribed biopharmaceutical, means a significant fraction of patients exposed to biologic agents will experience a secondary loss of response to one or more of the drugs. In clinical settings, immunogenicity may be caused by several factors, both patient related (e.g., underlying chronic disease, systemic immune burden, including previous biologic therapy failure, and [epi]genetic background) and treatment related (e.g., dose and administration regimens, drug physical structure, photostability, temperature, and agitation). Here, we outline these elements in detail to enhance biopharmaceutical delivery and therapy for patients with IBD. Moreover, concurrent immunomodulator medication may reduce the risks of ADA generation, especially when using the chimeric drug infliximab. Summarizing the latest developments and knowledge in the field, this review aims to provide strategies to prevent ADA production and information on managing non-responsiveness or loss of response to biologics. Better understanding of the molecular mechanisms underlying the formation of ADAs and the critical factors influencing the immunogenicity of biopharmaceuticals may lead to improved health outcomes in the IBD community that may benefit both the individual patient and society through lower healthcare expenses.
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Affiliation(s)
- Ole Haagen Nielsen
- Department of Gastroenterology D112, Herlev Hospital, University of Copenhagen, Borgmester Ib Juuls Vej 1, 2730 Herlev, Copenhagen, Denmark.
| | - Alexander Hammerhøj
- Department of Gastroenterology D112, Herlev Hospital, University of Copenhagen, Borgmester Ib Juuls Vej 1, 2730 Herlev, Copenhagen, Denmark
| | - Mark Andrew Ainsworth
- Department of Gastroenterology, Odense University Hospital, University of Southern Denmark, Odense, Denmark
| | - John Gubatan
- Department of Gastroenterology & Hepatology, Stanford University School of Medicine, Palo Alto, CA, USA
| | - Geert D'Haens
- Department of Gastroenterology and Hepatology, Amsterdam University Medical Center, Amsterdam, The Netherlands
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Dharmaraj R, Lemon TP, Elmaoued R, Castillo RO, Alkhouri R. Infusion Reactions to Infliximab in Pediatric Patients with Inflammatory Bowel Disease. CHILDREN (BASEL, SWITZERLAND) 2024; 11:1366. [PMID: 39594941 PMCID: PMC11592503 DOI: 10.3390/children11111366] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/24/2024] [Revised: 11/02/2024] [Accepted: 11/07/2024] [Indexed: 11/28/2024]
Abstract
Infliximab (IFX) is a recombinant DNA-derived chimeric IgG monoclonal antibody protein that inhibits tumor necrosis factor alpha (TNF-α). IFX, like other agents derived from foreign proteins, can cause infusion reactions both during and after the infusion. The incidence of infusion reactions ranges between 0% and 15% in pediatric patients. The potential underlying mechanisms for these reactions may include anaphylaxis and anaphylactoid reactions, cytokine release syndrome, serum sickness-like reactions, and the development of antibodies against IFX. Several precautions can help reduce the risk of a new infusion reaction, such as a gradual increase in the infusion rate, scheduled infusions, and administering premedication or immunomodulators alongside IFX. Acute mild to moderate reactions often resolve spontaneously after a temporary cessation of the infusion or reduction in the infusion rate. Strategies like graded dose challenges and premedication can be utilized to prevent recurrence. In cases of severe reactions, desensitization or switching to an alternative biologic may be considered. This article aims to review the most recent guidelines for managing IFX-related infusion reactions in pediatric patients with inflammatory bowel disease (IBD), relying on the best available evidence.
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Affiliation(s)
- Rajmohan Dharmaraj
- Division of Gastroenterology, Department of Pediatrics, University of New Mexico, Albuquerque, NM 87131, USA; (T.P.L.); (R.E.); (R.O.C.); (R.A.)
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3
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Wride AM, Chen GF, Spaulding SL, Tkachenko E, Cohen JM. Biologics for Psoriasis. Dermatol Clin 2024; 42:339-355. [PMID: 38796266 DOI: 10.1016/j.det.2024.02.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/28/2024]
Abstract
Biologic therapies targeting tumor necrosis factor alpha (TNF-α) (infliximab, adalimumab, certolizumab, etanercept), the p40 subunit shared by IL-12 and IL-23 (ustekinumab), the p19 subunit of IL-23 (guselkumab, tildrakizumab, risankizumab), IL-17A (secukinumab, ixekizumab), IL-17-RA (brodalumab) and both IL-17A and IL-17F (bimekizumab) have revolutionized the treatment of psoriasis. In both the short and long term, risankizumab had highest Psoriasis Area and Severity Index 90 scores compared to other oral and injectable biologics. IL-23 inhibitors had lowest rates of short-term and long-term adverse events and most favorable long-term risk-benefit profile compared to IL-17, IL-12/23, and TNF-α inhibitors.
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Affiliation(s)
- Anthony Mitchel Wride
- Department of Dermatology, Yale School of Medicine, Yale University, 15 York Street, New Haven, CT 06510, USA
| | - Gloria F Chen
- Department of Dermatology, Yale School of Medicine, Yale University, 15 York Street, New Haven, CT 06510, USA
| | - Sarah L Spaulding
- Department of Dermatology, Yale School of Medicine, Yale University, 15 York Street, New Haven, CT 06510, USA
| | - Elizabeth Tkachenko
- Department of Dermatology, Yale School of Medicine, Yale University, 15 York Street, New Haven, CT 06510, USA
| | - Jeffrey M Cohen
- Department of Dermatology, Yale School of Medicine, Yale University, 15 York Street, New Haven, CT 06510, USA.
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Rosenthal B, Aulakh S, Patel PV, Wong JT, Ali S. Direct transition from rapid-infusion originator to rapid-infusion biosimilar tumor necrosis factor inhibitor in children with inflammatory bowel disease: A case series. Am J Health Syst Pharm 2024; 81:61-65. [PMID: 37773728 PMCID: PMC11484643 DOI: 10.1093/ajhp/zxad217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Indexed: 10/01/2023] Open
Abstract
PURPOSE Biosimilar tumor necrosis factor inhibitors (b-TNFi) reduce healthcare costs and maintain equal efficacy when compared to their originator counterparts (o-TNFi). Current practice is to start patients on a slower standard infusion rate during the initial transition from an o-TNFi to a b-TNFi. There is a knowledge gap around switching from rapid originator infusion to rapid biosimilar infusion in the pediatric inflammatory bowel disease (IBD) population. SUMMARY We present a case series of 8 pediatric patients with IBD who were switched from a rapid-infusion o-TNFi to a rapid-infusion b-TNFi from 2016 through 2022. Our primary interest was safety, which we evaluated based on the occurrence of infusion reactions or need for new premedications within the first 6 months of starting a b-TNFi. We also examined effectiveness through the incidence of IBD-related hospitalizations, TNFi failure, and need for co-medication or dose escalation over the same period. In our cohort, 4 patients had Crohn's disease and 4 had ulcerative colitis. All patients were switched to a biosimilar for nonmedical reasons. During the follow-up period, no patients had infusion reactions necessitating new premedications, serious adverse events, or medication nonresponse. CONCLUSION Patients who directly transitioned from a rapid-infusion o-TNFi to a rapid-infusion b-TNFi did not experience serious adverse events. Given the fiscal and patient experience advantages of rapid-rate infusions, larger studies are needed to consider a change in practice.
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Affiliation(s)
| | - Sabreen Aulakh
- University of California San Francisco, University of California San Francisco Benioff Children’s Hospital, San Francisco, CA, USA
| | - Perseus V Patel
- Department of Pediatrics, University of California San Francisco, San Francisco, CA, USA
| | - Jason T Wong
- University of California San Francisco Benioff Children’s Hospital Oakland, Oakland, CA, USA
| | - Sabina Ali
- University of California San Francisco, University of California San Francisco Benioff Children’s Hospital Oakland, Oakland, CA, USA
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Balan RG, Deleanu DM, Pintea I, Dobrican Baruta CT, Man MA, Bocsan IC, Muntean IA. Managing Severe Adverse Reactions to Biologicals in Severe Asthma. Biomedicines 2023; 11:3108. [PMID: 38137329 PMCID: PMC10740468 DOI: 10.3390/biomedicines11123108] [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: 10/11/2023] [Revised: 11/16/2023] [Accepted: 11/17/2023] [Indexed: 12/24/2023] Open
Abstract
BACKGROUND The use of biological agents in the treatment of various inflammatory and malignancy conditions has expanded rapidly. However, these agents can induce hypersensitivity reactions, posing significant clinical challenges. METHODS We conducted a retrospective study that included nine patients with severe asthma who experienced hypersensitivity reactions to biological agents (omalizumab, benralizumab and dupilumab). RESULTS Hypersensitivity reactions to biologicals in severe asthma were observed in 9 of 68 patients treated. In five cases, treatment was stopped or changed to another available biological, and for four patients administered under close surveillance, titrated provocation or desensitization was applied. Successful desensitization was achieved in three of the patients, allowing them to continue therapy without adverse reactions. Improvements in asthma control were observed post-desensitization, leading to the reduced need for systemic steroid treatments and an increase in quality of life. CONCLUSIONS This study highlights the importance of recognizing hypersensitivity reactions to biologicals to have an appropriate approach for patients with severe asthma. As an effective approach for patients experiencing hypersensitivity reactions to biological agents, desensitization allows treatment continuation.
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Affiliation(s)
- Radu-Gheorghe Balan
- Department of Allergology and Immunology, “Iuliu Hațieganu” University of Medicine and Pharmacy, Str. Croitorilor 19–21, 400058 Cluj-Napoca, Romania; (R.-G.B.); (D.M.D.); (I.C.B.); (I.A.M.)
- Department of Science and Technology, George Emil Palade University of Medicine, Pharmacy, Science and Technology, 540067 Târgu Mureş, Romania
| | - Diana Mihaela Deleanu
- Department of Allergology and Immunology, “Iuliu Hațieganu” University of Medicine and Pharmacy, Str. Croitorilor 19–21, 400058 Cluj-Napoca, Romania; (R.-G.B.); (D.M.D.); (I.C.B.); (I.A.M.)
- Department of Allergology, “Professor Doctor Octavian Fodor” Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania
- Department of Internal Medicine, “Professor Doctor Octavian Fodor” Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania
| | - Irena Pintea
- Department of Allergology and Immunology, “Iuliu Hațieganu” University of Medicine and Pharmacy, Str. Croitorilor 19–21, 400058 Cluj-Napoca, Romania; (R.-G.B.); (D.M.D.); (I.C.B.); (I.A.M.)
- Department of Allergology, “Professor Doctor Octavian Fodor” Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania
| | - Carmen Teodora Dobrican Baruta
- Department of Allergology and Immunology, “Iuliu Hațieganu” University of Medicine and Pharmacy, Str. Croitorilor 19–21, 400058 Cluj-Napoca, Romania; (R.-G.B.); (D.M.D.); (I.C.B.); (I.A.M.)
- Department of Allergology, “Professor Doctor Octavian Fodor” Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania
| | - Milena Adina Man
- Department of Medical Sciences, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania;
- Department of Pneumology, “Leon Daniello” Clinical Hospital of Pulmonology, 400332 Cluj-Napoca, Romania
| | - Ioana Corina Bocsan
- Department of Allergology and Immunology, “Iuliu Hațieganu” University of Medicine and Pharmacy, Str. Croitorilor 19–21, 400058 Cluj-Napoca, Romania; (R.-G.B.); (D.M.D.); (I.C.B.); (I.A.M.)
- Department of Pharmacology, Toxicology and Clinical Pharmacology, “Iuliu Hațieganu” University of Medicine and Pharmacy, 400337 Cluj-Napoca, Romania
- Almedo—Allergology and Clinical Immunology Outpatient Clinic, 400394 Cluj-Napoca, Romania
| | - Ioana Adriana Muntean
- Department of Allergology and Immunology, “Iuliu Hațieganu” University of Medicine and Pharmacy, Str. Croitorilor 19–21, 400058 Cluj-Napoca, Romania; (R.-G.B.); (D.M.D.); (I.C.B.); (I.A.M.)
- Department of Allergology, “Professor Doctor Octavian Fodor” Regional Institute of Gastroenterology and Hepatology, 400162 Cluj-Napoca, Romania
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Oylumlu E, Uzel G, Durmus L, Ciraci C. IgE Immune Complexes Mitigate Eosinophilic Immune Responses through NLRC4 Inflammasome. Mediators Inflamm 2023; 2023:3224708. [PMID: 37885469 PMCID: PMC10599938 DOI: 10.1155/2023/3224708] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/19/2023] [Revised: 09/25/2023] [Accepted: 09/30/2023] [Indexed: 10/28/2023] Open
Abstract
Immune complexes (ICs) skew immune responses toward either a pro- or anti-inflammatory direction based on the type of stimulation. Immunoglobulin E (IgE) is associated with Th2 immune responses and known to activate innate immune cells. However, roles of antigen (Ag)-specific-IgE ICs in regulating human eosinophil responses remain elusive; therefore, this study builts upon the mechanism of which ovalbumin (Ova)-IgE ICs affects eosinophilic responses utilizing human EoL-1 cell line as a model. Eosinophils are granulocytes functioning through pattern recognition receptors (PRRs) and destructive granule contents in allergic inflammation and parasitic infections. One of the PRRs that eosinophils express is NLRC4, a member of the CARD domain containing nucleotide-binding oligomerization (NOD)-like receptor (NLR) family. Upon recognition of its specific ligand flagellin, NLRC4 inflammasome is formed and leads to the release of interleukin-1β (IL-1β). We exhibited that Ova-IgE ICs induced the NLRC4-inflammasome components, including NLRC4, caspase-1, intracellular IL-1β, and secretion of IL-1β, as well as the granule contents MMP9, TIMP1, and TIMP2 proteins via TLR2 signaling; these responses were suppressed, when NLRC4 inflammasome got actived in the presence of ICs. Furthermore, Ova-IgE ICs induced mRNA expressions of MMP9, TIMP2, and ECP and protein expressions of MMP9 and TIMP2 in EoL-1 through FcɛRII. Interestingly, TLR2 ligand and Ova-IgE ICs costimulation elevated the number of CD63+ cells, a degranulation marker, as compared to the native IgE. Collectively, our findings provide a mechanism for the impacts of Ova-IgE ICs on eosinophilic responses via NLRC4-inflammasome and may help understand eosinophil-associated diseases, including chronic eosinophilic pneumonia, eosinophilic esophagitis, eosinophilic granulomatosis, parasitic infections, allergy, and asthma.
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Affiliation(s)
- Ece Oylumlu
- Molecular Biology and Genetics Department, Istanbul Technical University, Istanbul 34469, Turkey
| | - Goksu Uzel
- Molecular Biology and Genetics Department, Istanbul Technical University, Istanbul 34469, Turkey
| | - Lubeyne Durmus
- Molecular Biology and Genetics Department, Istanbul Technical University, Istanbul 34469, Turkey
| | - Ceren Ciraci
- Molecular Biology and Genetics Department, Istanbul Technical University, Istanbul 34469, Turkey
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Shentova-Eneva RR, Kofinova DR, Baycheva MZ, Hadzhiyski PG, Naydenov HB, Yaneva PG, Lazarova EA. Anti-tumor necrosis factor therapy in Bulgarian pediatric patients with inflammatory bowel disease - an 8-year experience of a referral center. Folia Med (Plovdiv) 2023; 65:605-611. [PMID: 37655379 DOI: 10.3897/folmed.65.e84368] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2022] [Accepted: 06/10/2022] [Indexed: 09/02/2023] Open
Abstract
INTRODUCTION Anti-tumor necrosis factor (anti-TNF) therapy has become a mainstay in the treatment of patients with inflammatory bowel disease over the past few decades.
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Abstract
The spondyloarthritides are a diverse group of distinct yet interrelated disease processes with overlapping clinical features. They are ankylosing spondylitis, reactive arthritis, inflammatory bowel disease-associated arthritis, and psoriatic arthritis. Genetically, these disease processes have been linked by the presence of HLA-B27. They manifest with axial and peripheral symptoms, such as inflammatory back pain, enthesitis, oligoarthritis, and dactylitis. The onset of symptoms can begin before the age of 45; however, because of the wide range of signs and symptoms, diagnosis can be delayed, leading to unchecked inflammation, structural damage, and later, restriction in physical mobility.
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Affiliation(s)
- Hope A Taitt
- Department of Emergency Medicine, Kings County Hospital, SUNY Downstate Medical Center, Kings County Hospital Center, Room CG65, 451 Clarkson Avenue, Brooklyn, NY 11203, USA
| | - Rithvik Balakrishnan
- Department of Emergency Medicine, Kings County Hospital, SUNY Downstate Medical Center, Kings County Hospital Center, Room CG65, 451 Clarkson Avenue, Brooklyn, NY 11203, USA.
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Abushamma S, Walker T, Garza K, Chen L, Nix D, Chen CH. Accelerated Infliximab Infusion Safety and Tolerability Is Non-inferior to Standard Infusion Protocol in Inflammatory Bowel Disease Patients: A Randomized Controlled Study. CROHN'S & COLITIS 360 2023; 5:otad022. [PMID: 37288326 PMCID: PMC10243871 DOI: 10.1093/crocol/otad022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/10/2023] [Indexed: 06/09/2023] Open
Abstract
BACKGROUND AND AIM Infliximab is typically given over an infusion time of 2 hours, leading to a significant burden in inflammatory bowel disease (IBD) patients. We aimed to determine the safety and cost-effectiveness of an accelerated infliximab infusion of 1 hour, compared with the standard 2-hour infusion. METHODS Open-label randomized trial where IBD patients receiving maintenance infliximab infusions were randomly assigned to 1- and 2-hour infusion groups, corresponding to study and control groups, respectively. The primary outcome was the rate of infusion reactions. Secondary outcomes were assessment of the effect of premedications and immunomodulators on the rate of infusion reactions, and cost-effectiveness analysis. The cost-effectiveness analysis was based on direct nursing costs for the infusion time, indirect infusion center costs, and cost of productivity loss for patients. This trial is registered with ClinicalTrials.gov, NCT05340764. RESULTS From November 2020 to November 2021, 96 patients were randomly assigned: 51 (53%) to the 1-hour infusion group and 45 (47%) to the 2-hour infusion group. Over a median time of 1 year, 309 infusions were administered in the control group, and 376 in the study group. Fifty-seven (18%) infusions in the control group and 45 (12%) infusions in the study group experienced an infusion reaction. The only infusion reaction was asymptomatic hypotension not requiring infusion discontinuation. No other infusion reactions (mild or moderate/severe) were seen. Diphenhydramine was associated with an increased rate of infusion reactions (OR 2.04 [95% CI 1.18-3.52], P = .01). The average costs were estimated to reduce by 37% in the accelerated infusion group. CONCLUSIONS Accelerated 1-hour infusions are non-inferior in safety and superior in cost-effectiveness compared with standard 2-hour infusions in IBD patients receiving maintenance infliximab infusions. TRIAL IDENTIFICATION NUMBER Registered with ClinicalTrials.gov, NCT05340764.
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Affiliation(s)
- Suha Abushamma
- Division of Gastroenterology, John T. Milliken Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA
| | - Ted Walker
- Division of Gastroenterology, John T. Milliken Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA
| | - Kevin Garza
- Division of General Medicine, John T. Milliken Department of Medicine, Washington University School of Medicine, St. Louis, Missouri, USA
| | - Ling Chen
- Division of Biostatistics, Washington University School of Medicine, Saint Louis, Missouri, USA
| | - Darren Nix
- Division of Gastroenterology, John T. Milliken Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA
| | - Chien-Huan Chen
- Division of Gastroenterology, John T. Milliken Department of Medicine, Washington University School of Medicine, Saint Louis, Missouri, USA
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10
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Grillo TG, Silveira CFDSMP, Quaglio AEV, Dutra RDM, Baima JP, Bazan SGZ, Sassaki LY. Acute heart failure as an adverse event of tumor necrosis factor inhibitor therapy in inflammatory bowel disease: A review of the literature. World J Cardiol 2023; 15:217-228. [PMID: 37274378 PMCID: PMC10237008 DOI: 10.4330/wjc.v15.i5.217] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Revised: 02/09/2023] [Accepted: 04/12/2023] [Indexed: 05/19/2023] Open
Abstract
Tumor necrosis factor inhibitors (anti-TNFs) are widely used therapies for the treatment of inflammatory bowel diseases (IBD); however, their administration is not risk-free. Heart failure (HF), although rare, is a potential adverse event related to administration of these medications. However, the exact mechanism of development of HF remains obscure. TNFα is found in both healthy and damaged hearts. Its effects are concentration- and receptor-dependent, promoting either cardio-protection or cardiomyocyte apoptosis. Experimental rat models with TNFα receptor knockout showed increased survival rates, less reactive oxygen species formation, and improved diastolic left ventricle pressure. However, clinical trials employing anti-TNF therapy to treat HF had disappointing results, suggesting abolishment of the cardioprotective properties of TNFα, making cardiomyocytes susceptible to apoptosis and oxidation. Thus, patients with IBD who have risk factors should be screened for HF before initiating anti-TNF therapy. This review aims to discuss adverse events associated with the administration of anti-TNF therapy, with a focus on HF, and propose some approaches to avoid cardiac adverse events in patients with IBD.
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Affiliation(s)
- Thais Gagno Grillo
- Department of Internal Medicine, Medical School, São Paulo State University, Botucatu, Botucatu 18618686, Brazil
| | | | - Ana Elisa Valencise Quaglio
- Department of Biophysics and Pharmacology, Institute of Biosciences, São Paulo State University, Botucatu, Botucatu 18618689, Brazil
| | - Renata de Medeiros Dutra
- Department of Internal Medicine, Medical School, São Paulo State University, Botucatu, Botucatu 18618686, Brazil
| | - Julio Pinheiro Baima
- Department of Internal Medicine, Medical School, São Paulo State University, Botucatu, Botucatu 18618686, Brazil
| | - Silmeia Garcia Zanati Bazan
- Department of Internal Medicine, Medical School, São Paulo State University, Botucatu, Botucatu 18618686, Brazil
| | - Ligia Yukie Sassaki
- Department of Internal Medicine, Medical School, São Paulo State University, Botucatu, Botucatu 18618686, Brazil.
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Alhazmi HA, Albratty M. Analytical Techniques for the Characterization and Quantification of Monoclonal Antibodies. Pharmaceuticals (Basel) 2023; 16:291. [PMID: 37259434 PMCID: PMC9967501 DOI: 10.3390/ph16020291] [Citation(s) in RCA: 33] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 01/17/2023] [Accepted: 01/18/2023] [Indexed: 08/12/2023] Open
Abstract
Monoclonal antibodies (mAbs) are a fast-growing class of biopharmaceuticals. They are widely used in the identification and detection of cell makers, serum analytes, and pathogenic agents, and are remarkably used for the cure of autoimmune diseases, infectious diseases, or malignancies. The successful application of therapeutic mAbs is based on their ability to precisely interact with their appropriate target sites. The precision of mAbs rely on the isolation techniques delivering pure, consistent, stable, and safe lots that can be used for analytical, diagnostic, or therapeutic applications. During the creation of a biologic, the key quality features of a particular mAb, such as structure, post-translational modifications, and activities at the biomolecular and cellular levels, must be characterized and profiled in great detail. This implies the requirement of powerful state of the art analytical techniques for quality control and characterization of mAbs. Until now, various analytical techniques have been developed to characterize and quantify the mAbs according to the regulatory guidelines. The present review summarizes the major techniques used for the analyses of mAbs which include chromatographic, electrophoretic, spectroscopic, and electrochemical methods in addition to the modifications in these methods for improving the quality of mAbs. This compilation of major analytical techniques will help students and researchers to have an overview of the methodologies employed by the biopharmaceutical industry for structural characterization of mAbs for eventual release of therapeutics in the drug market.
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Affiliation(s)
- Hassan A. Alhazmi
- Department of Pharmaceutical Chemistry and Pharmacognosy, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia
- Substance Abuse and Toxicology Research Centre, Jazan University, Jazan 45142, Saudi Arabia
| | - Mohammed Albratty
- Department of Pharmaceutical Chemistry and Pharmacognosy, College of Pharmacy, Jazan University, Jazan 45142, Saudi Arabia
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12
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Khan DA, Banerji A, Blumenthal KG, Phillips EJ, Solensky R, White AA, Bernstein JA, Chu DK, Ellis AK, Golden DBK, Greenhawt MJ, Horner CC, Ledford D, Lieberman JA, Oppenheimer J, Rank MA, Shaker MS, Stukus DR, Wallace D, Wang J, Khan DA, Golden DBK, Shaker M, Stukus DR, Khan DA, Banerji A, Blumenthal KG, Phillips EJ, Solensky R, White AA, Bernstein JA, Chu DK, Ellis AK, Golden DBK, Greenhawt MJ, Horner CC, Ledford D, Lieberman JA, Oppenheimer J, Rank MA, Shaker MS, Stukus DR, Wallace D, Wang J. Drug allergy: A 2022 practice parameter update. J Allergy Clin Immunol 2022; 150:1333-1393. [PMID: 36122788 DOI: 10.1016/j.jaci.2022.08.028] [Citation(s) in RCA: 246] [Impact Index Per Article: 82.0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/17/2022] [Revised: 08/18/2022] [Accepted: 08/30/2022] [Indexed: 12/14/2022]
Affiliation(s)
- David A Khan
- Department of Internal Medicine, Division of Allergy and Immunology, University of Texas Southwestern Medical Center, Dallas, Tex
| | - Aleena Banerji
- Department of Internal Medicine, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, Mass
| | - Kimberly G Blumenthal
- Department of Internal Medicine, Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, Mass
| | - Elizabeth J Phillips
- Institute for Immunology and Infectious Diseases, Murdoch University, Murdoch, Western Australia; Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn
| | - Roland Solensky
- Corvallis Clinic, Oregon State University/Oregon Health Science University College of Pharmacy, Corvallis, Ore
| | - Andrew A White
- Department of Allergy, Asthma and Immunology, Scripps Clinic, San Diego, Calif
| | - Jonathan A Bernstein
- Department of Internal Medicine, Division of Immunology, Allergy Section, University of Cincinnati College of Medicine, Cincinnati, Ohio
| | - Derek K Chu
- Department of Health Research Methods, Evidence and Impact, McMaster University, Hamilton, Ontario, Canada; Department of Medicine, McMaster University, Hamilton, Ontario, Canada; The Research Institute of St Joe's Hamilton, Hamilton, Ontario, Canada
| | - Anne K Ellis
- Division of Allergy and Immunology, Department of Medicine, Queen's University, Kingston, Ontario, Canada
| | - David B K Golden
- Division of Allergy and Clinical Immunology, Johns Hopkins University School of Medicine, Baltimore, Md
| | - Matthew J Greenhawt
- Food Challenge and Research Unit Section of Allergy and Immunology, Children's Hospital Colorado University of Colorado School of Medicine, Aurora, Colo
| | - Caroline C Horner
- Department of Pediatrics, Division of Allergy Pulmonary Medicine, Washington University School of Medicine, St Louis, Mo
| | - Dennis Ledford
- Division of Allergy and Immunology, Department of Medicine, University of South Florida Morsani College of Medicine, Tampa, Fla; James A. Haley Veterans Affairs Hospital, Tampa, Fla
| | - Jay A Lieberman
- Division of Allergy and Immunology, The University of Tennessee Health Science Center, Memphis, Tenn
| | - John Oppenheimer
- Division of Allergy, Rutgers New Jersey Medical School, Rutgers, NJ
| | - Matthew A Rank
- Division of Allergy, Asthma, and Clinical Immunology, Mayo Clinic in Arizona, Scottsdale, Ariz
| | - Marcus S Shaker
- Department of Pediatrics, Dartmouth-Hitchcock Medical Center, Lebanon, NH
| | - David R Stukus
- Division of Allergy and Immunology, Nationwide Children's Hospital, Columbus, Ohio; The Ohio State University College of Medicine, Columbus, Ohio
| | - Dana Wallace
- Nova Southeastern Allopathic Medical School, Fort Lauderdale, Fla
| | - Julie Wang
- Division of Allergy and Immunology, Department of Pediatrics, The Elliot and Roslyn Jaffe Food Allergy Institute, Icahn School of Medicine at Mount Sinai, New York, NY
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Biologics for Inflammatory Bowel Disease in Clinical Practice: A Calabria (Southern Italy) Prospective Pharmacovigilance Study. Pharmaceutics 2022; 14:pharmaceutics14112449. [PMID: 36432640 PMCID: PMC9696291 DOI: 10.3390/pharmaceutics14112449] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/14/2022] [Revised: 11/05/2022] [Accepted: 11/11/2022] [Indexed: 11/16/2022] Open
Abstract
BACKGROUND The use of immune-modifying biological agents has markedly changed the clinical course and the management of Inflammatory bowel diseases (IBDs). Active post-marketing surveillance programs are fundamental to early recognize expected and unexpected adverse events (AEs), representing a powerful tool to better determine the safety profiles of biologics in a real-world setting. METHODS This study aimed to identify the occurrence of AEs and therapeutic failures linked to biological drugs used in gastroenterology units during a prospective pharmacovigilance program in Southern Italy. Patients affected by IBDs and treated with a biologic agent, from 1 January 2019, to 31 December 2021 (study period) in three gastroenterology units were enrolled. RESULTS Overall, 358 patients with a diagnosis of active Crohn's disease or ulcerative colitis satisfying inclusion criteria have been enrolled. Infliximab (IFX) was the most administered drug at the index date (214; 59.8%), followed by Adalimumab (ADA; 89; 24.9%), Golimumab (GOL; 37; 10.3%), Vedolizumab (VDZ; 17; 4.7%) and Ustekimumab (UST; 1; 0.3%). Seventy-three patients (20.4%) experienced at least one AE, while 62 patients (17.3%) had therapeutic ineffectiveness. No serious AEs were reported in the follow-up period in the enrolled patients. AEs have been described with IFX (50/214; p = 0.47), GOL (7/37; p = 0.78), ADA (13/89; p = 0.18), and VDZ (3/17; p = 0.52), no AEs have been noticed with UST (0/1). CONCLUSIONS Based on the low rate of AEs observed and withdrawal from treatment, our data seem to corroborate the favorable beneficial/risk profile of biologics for IBDs.
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14
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Efficacy and Safety of Infliximab Retreatment in Crohn's Disease: A Multicentre, Prospective, Observational Cohort (REGAIN) Study from the GETAID. Am J Gastroenterol 2022; 117:1482-1490. [PMID: 35973142 DOI: 10.14309/ajg.0000000000001842] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/21/2021] [Accepted: 05/06/2022] [Indexed: 12/11/2022]
Abstract
INTRODUCTION The objective of this study was to describe the efficacy and safety of infliximab (IFX) reintroduction in Crohn's disease (CD) after stopping for loss of response or intolerance. METHODS We conducted a prospective multicenter observational cohort study including adult patients with clinically (CD Activity Index >150) and objectively active luminal CD in whom IFX was reintroduced after at least 6 months of discontinuation. The reasons for the initial discontinuation could be a secondary loss of response or IFX intolerance. The reintroduction schedule included 3 IFX infusions at weeks 0, 4, and 8, after a systematic premedication. The primary end point was the efficacy of IFX retreatment at week 26 defined by a CD Activity Index of <150 in the absence of IFX discontinuation or use of corticosteroids, surgery, or other biologic. RESULTS At week 26, 24 patients (35%) among the 69 analyzed reached the primary end point. No significant difference was observed between rates of clinical remission at week 26 in patients with prior LOR (n = 48) and those with IFX intolerance (n = 21) (35% and 33%, P = 0.87, respectively). Thirty-two acute infusion reactions were recorded in 27 patients, leading to withdrawal of IFX in 20 patients. No pharmacokinetic characteristic at baseline but detection of positive anti-drug antibodies at week 4 was predictive of IFX failure or infusion reaction at week 26. DISCUSSION In this first prospective cohort study, IFX retreatment was safe and effective in one-third of the patients with CD, regardless the reason of prior discontinuation. Early detection of anti-drug antibodies can predict subsequent IFX reintroduction failure and infusion reactions.
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15
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Ong WC, Lim MS, Chan E, Lim TCT, Lim TG, Chan W. A quality improvement project reduces time spent at an inflammatory bowel disease infusion center with accelerated infliximab infusion protocol. JGH OPEN 2022; 6:470-476. [PMID: 35822121 PMCID: PMC9260204 DOI: 10.1002/jgh3.12776] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/06/2022] [Revised: 04/29/2022] [Accepted: 05/15/2022] [Indexed: 11/11/2022]
Abstract
Background and Aim Methods Results Conclusion
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Affiliation(s)
- Wan Chee Ong
- Department of Pharmacy Singapore General Hospital Singapore
| | - Miao Shan Lim
- Department of Gastroenterology and Hepatology Singapore General Hospital Singapore
| | - Elaine Chan
- Department of Nursing Singapore General Hospital Singapore
| | | | - Teong Guan Lim
- Department of Pharmacy Singapore General Hospital Singapore
| | - Webber Chan
- Department of Gastroenterology and Hepatology Singapore General Hospital Singapore
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16
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Joseph M, Kochanski J, Goyal A. A Case of Epinephrin-associated Refractory Hypotension Secondary to Lactic Acidosis. Inflamm Bowel Dis 2022; 28:e49-e50. [PMID: 34718560 DOI: 10.1093/ibd/izab268] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/28/2022]
Affiliation(s)
- Michael Joseph
- Department of Pediatrics, Stanford University, Palo Alto, CA, USA
| | - Justin Kochanski
- Department of Pediatrics, Stanford University, Palo Alto, CA, USA
| | - Alka Goyal
- Department of Pediatric Gastroenterology, Stanford University, Palo Alto, CA, USA
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17
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Hypersensitivity Reactions and Immune-Related Adverse Events to Immune Checkpoint Inhibitors: Approaches, Mechanisms, and Models. Immunol Allergy Clin North Am 2022; 42:285-305. [DOI: 10.1016/j.iac.2021.12.006] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
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18
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Casey J. Effectiveness of scheduled vital signs assessment during infliximab infusions in detecting infusion reactions: a multi-centre retrospective data review. BRITISH JOURNAL OF NURSING (MARK ALLEN PUBLISHING) 2022; 31:S16-S22. [PMID: 35094545 DOI: 10.12968/bjon.2022.31.2.s16] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/14/2023]
Abstract
PURPOSE To determine if scheduled vital signs monitoring is useful in the detection of infusion reactions to infliximab (IFX). METHODS The infusion records of 35,988 IFX infusions completed in 2017 were reviewed for infusion reactions that occurred during the infusion, which were then examined further to determine how those infusion reactions were detected. RESULTS Of the 90 complete infusion reaction records reviewed, no infusion reactions (0) were detected by scheduled vital signs assessment. CONCLUSIONS According to the infusion reaction data reviewed, scheduled vital sign assessment did not detect any infusion reactions and may not be necessary for the purpose of monitoring patients during infusions for early detection of infusion reactions. Previous research into IFX infusion reactions reviewed also concluded that scheduled vital signs assessment may not be helpful in the detection of infusion reactions and, in many cases, vital signs did not vary significantly enough from baseline to signal an infusion reaction.
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Affiliation(s)
- Julia Casey
- The Clinical Educator for Coverdale Infusion Clinics Inc. She has gained expertise in infusion therapy of monoclonal antibodies, having worked in this area in the private sector for more than nine years. Julia's poster abstract on vital signs assessment during infusion won first place at the 2019 CVAA conference
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19
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Shi D, Beasock D, Fessler A, Szebeni J, Ljubimova JY, Afonin KA, Dobrovolskaia MA. To PEGylate or not to PEGylate: Immunological properties of nanomedicine's most popular component, polyethylene glycol and its alternatives. Adv Drug Deliv Rev 2022; 180:114079. [PMID: 34902516 PMCID: PMC8899923 DOI: 10.1016/j.addr.2021.114079] [Citation(s) in RCA: 238] [Impact Index Per Article: 79.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2021] [Revised: 12/01/2021] [Accepted: 12/03/2021] [Indexed: 01/03/2023]
Abstract
Polyethylene glycol or PEG has a long history of use in medicine. Many conventional formulations utilize PEG as either an active ingredient or an excipient. PEG found its use in biotechnology therapeutics as a tool to slow down drug clearance and shield protein therapeutics from undesirable immunogenicity. Nanotechnology field applies PEG to create stealth drug carriers with prolonged circulation time and decreased recognition and clearance by the mononuclear phagocyte system (MPS). Most nanomedicines approved for clinical use and experimental nanotherapeutics contain PEG. Among the most recent successful examples are two mRNA-based COVID-19 vaccines that are delivered by PEGylated lipid nanoparticles. The breadth of PEG use in a wide variety of over the counter (OTC) medications as well as in drug products and vaccines stimulated research which uncovered that PEG is not as immunologically inert as it was initially expected. Herein, we review the current understanding of PEG's immunological properties and discuss them in the context of synthesis, biodistribution, safety, efficacy, and characterization of PEGylated nanomedicines. We also review the current knowledge about immunological compatibility of other polymers that are being actively investigated as PEG alternatives.
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Key Words
- Poly(ethylene)glycol, PEG, immunogenicity, immunology, nanomedicine, toxicity, anti-PEG antibodies, hypersensitivity, synthesis, drug delivery, biotherapeutics
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Affiliation(s)
- Da Shi
- Nanotechnology Characterization Lab, Frederick National Laboratory for Cancer Research Sponsored by the National Cancer Institute, Frederick, MD, USA
| | - Damian Beasock
- University of North Carolina Charlotte, Charlotte, NC, USA
| | - Adam Fessler
- University of North Carolina Charlotte, Charlotte, NC, USA
| | - Janos Szebeni
- Nanomedicine Research and Education Center, Institute of Translational Medicine, Semmelweis University, Budapest, Hungary; SeroScience LCC, Budapest, Hungary; Department of Nanobiotechnology and Regenerative Medicine, Faculty of Health, Miskolc University, Miskolc, Hungary
| | | | | | - Marina A Dobrovolskaia
- Nanotechnology Characterization Lab, Frederick National Laboratory for Cancer Research Sponsored by the National Cancer Institute, Frederick, MD, USA.
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Immunomodulatory Agents for Treatment of Patients with Inflammatory Bowel Disease (Review safety of anti-TNF, Anti-Integrin, Anti IL-12/23, JAK Inhibition, Sphingosine 1-Phosphate Receptor Modulator, Azathioprine / 6-MP and Methotrexate). Curr Gastroenterol Rep 2021; 23:30. [PMID: 34913108 DOI: 10.1007/s11894-021-00829-y] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 09/15/2021] [Indexed: 02/08/2023]
Abstract
PURPOSE OF THE REVIEW As treatment options for Inflammatory Bowel Disease (IBD) expand each class of medication will have specific safety concerns and side-effect profiles that need to be considered for optimal treatment of patients. We will review the most recent safety data for the newly approved immunomodulator therapies for the treatment of IBD. RECENT FINDINGS There are a growing number of publications outlining safety concerns for medications used to treat IBD. We reviewed safety profile of anti-tumor necrosis factor antibodies (TNF) with specific attention to combination therapy (anti-TNF plus immunomodulator). Recent publications have demonstrated increased risk of serious infection and malignancy (lymphoma and overall cancer rates) in patients receiving anti-TNF combination therapy when compared with patients receiving anti-TNF monotherapy or immunomodulator monotherapy. Recent publications on Janus Kinase Inhibitors indicate an increased risk of infection, specifically Herpes Zoster, and increased risk of major cardiovascular events and venous thromboembolic events resulting in a black box warning for the medication. In contrast, anti-interleukin 12/23 agents and gut selective anti-integrin antibody agents have demonstrated a favorable side-effect profile with low rates of infection and malignancy. The latest class of medications to be approved, sphingosine 1-phosphate (S1P) receptor modulators, have cardiac and infectious precautions. The field of IBD treatment is rapidly evolving with several mechanistic classes of medications now available. While corticosteroids continue to be associated with the greatest, overall, safety risks, each of the newer mechanistic classes have unique safety concerns. In the future, as we gain more experience with these agents, we will need to continue to evaluate the safety profile of our therapies used alone or in combination to make informed treatment decisions with our patients.
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Zvuloni M, Matar M, Levi R, Shouval DS, Shamir R, Assa A. High anti-TNFα Concentrations Are Not Associated With More Adverse Events in Pediatric Inflammatory Bowel Disease. J Pediatr Gastroenterol Nutr 2021; 73:717-721. [PMID: 34292219 DOI: 10.1097/mpg.0000000000003240] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/10/2022]
Abstract
ABSTRACT Anti-tumor necrosis factor alpha (anti-TNFα) therapy is commonly used to treat refractory pediatric inflammatory bowel disease (IBD) and carry risks for adverse events. We aimed to assess the relationship between anti-TNFα trough concentrations and adverse events rate among pediatric patients with IBD. The medical records of pediatric patients with IBD who were treated with anti-TNFα agents from 2015 to 2020 and had sequential monitoring of trough concentration (TC) were reviewed retrospectively for the presence of adverse events. The study cohort included 135 eligible patients (59 [43.7%] girls, mean age at diagnosis 12.9 [±3] years, 111 [82.2%] Crohn disease) who had 1589 measurements of TCs (1037 [63%] infliximab). During a median follow-up period of 1.7 years (IQR 1.1-2.7), we recorded 156 adverse events in 50 patients (37%). Higher TCs were not associated with higher rate of anti-TNFα-related adverse events whereas these events (excluding increase in liver transaminases) were associated with younger age.
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Affiliation(s)
- Maya Zvuloni
- The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv
| | - Manar Matar
- The institute of Gastroenterology, Nutrition and Liver diseases, Schneider Children's Hospital, Petach-Tikva
| | - Rachel Levi
- The institute of Gastroenterology, Nutrition and Liver diseases, Schneider Children's Hospital, Petach-Tikva
| | - Dror S Shouval
- The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv
- The institute of Gastroenterology, Nutrition and Liver diseases, Schneider Children's Hospital, Petach-Tikva
| | - Raanan Shamir
- The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv
- The institute of Gastroenterology, Nutrition and Liver diseases, Schneider Children's Hospital, Petach-Tikva
| | - Amit Assa
- The institute of Gastroenterology, Nutrition and Liver diseases, Schneider Children's Hospital, Petach-Tikva
- The Ben-Gurion University of the Negev, Beer Sheva, Israel
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22
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Abrantes FF, Moraes MPMD, Albuquerque Filho JMVD, Alencar JMD, Lopes AB, Pinto WBVDR, Souza PVSD, Oliveira EMLD, Oliveira ADSBD, Pedroso JL, Barsottini OGP. Immunosuppressors and immunomodulators in Neurology - Part I: a guide for management of patients underimmunotherapy. ARQUIVOS DE NEURO-PSIQUIATRIA 2021; 79:1012-1025. [PMID: 34816994 DOI: 10.1590/0004-282x-anp-2020-0593] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/05/2020] [Accepted: 03/12/2021] [Indexed: 11/22/2022]
Abstract
For patients with autoimmune diseases, the risks and benefits of immunosuppressive or immunomodulatory treatment are a matter of continual concern. Knowledge of the follow-up routine for each drug is crucial, in order to attain better outcomes and avoid new disease activity or occurrence of adverse effects. To achieve control of autoimmune diseases, immunosuppressive and immunomodulatory drugs act on different pathways of the immune response. Knowledge of the mechanisms of action of these drugs and their recommended doses, adverse reactions and risks of infection and malignancy is essential for safe treatment. Each drug has a specific safety profile, and management should be adapted for different circumstances during the treatment. Primary prophylaxis for opportunistic infections and vaccination are indispensable steps during the treatment plan, given that these prevent potential severe infectious complications. General neurologists frequently prescribe immunosuppressive and immunomodulatory drugs, and awareness of the characteristics of each drug is crucial for treatment success. Implementation of a routine before, during and after use of these drugs avoids treatment-related complications and enables superior disease control.
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Affiliation(s)
- Fabiano Ferreira Abrantes
- Universidade Federal de São Paulo, Departamento de Neurologia, Divisão de Neurologia Geral, São Paulo SP, Brazil
| | | | | | - Jéssica Monique Dias Alencar
- Universidade Federal de São Paulo, Departamento de Neurologia, Divisão de Neurologia Geral, São Paulo SP, Brazil
| | - Alexandre Bussinger Lopes
- Universidade Federal de São Paulo, Departamento de Neurologia, Divisão de Neurologia Geral, São Paulo SP, Brazil
| | | | - Paulo Victor Sgobbi de Souza
- Universidade Federal de São Paulo, Departamento de Neurologia, Divisão de Neurologia Geral, São Paulo SP, Brazil
| | | | | | - José Luiz Pedroso
- Universidade Federal de São Paulo, Departamento de Neurologia, Divisão de Neurologia Geral, São Paulo SP, Brazil
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23
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The Efficacy of Antihistamines in Preventing Reactions to Infliximab in Patients With Crohn Disease/Ulcerative Colitis: A Review of the Evidence. Gastroenterol Nurs 2021; 43:345-349. [PMID: 33003021 DOI: 10.1097/sga.0000000000000482] [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] [Indexed: 11/26/2022] Open
Abstract
Inflammatory bowel diseases, including Crohn disease and ulcerative colitis, are most often diagnosed during adolescence and young adulthood, with a rising incidence in pediatric populations. Infliximab is an effective treatment option for Crohn disease and ulcerative colitis. The most common adverse event with infliximab is an infusion reaction. Patients are often treated prophylactically with combinations of acetaminophen, intravenous steroid, and an antihistamine to prevent an infusion reaction. There is a high degree of practice variation regarding pretreatment for infliximab infusions, the efficacy of pretreatment with an antihistamine is unproven in preventing infusion-related reactions, and there is no national clinical standard. Unnecessary pretreatment in adolescence and young adulthood may be harmful, as this is a time to focus on developing self-care management skills. Antihistamine side effects including somnolence and dizziness may adversely affect adolescents and/or young adults' ability to complete schoolwork, drive, and transition toward autonomous management of their chronic illness. This report presents the findings of an evidence-based practice project reviewing the efficacy of pretreatment with an antihistamine in patients with Crohn disease and ulcerative colitis receiving infliximab. Practice implications are discussed.
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Abstract
The spondyloarthritides are a diverse group of distinct yet interrelated disease processes with overlapping clinical features. They are ankylosing spondylitis, reactive arthritis, inflammatory bowel disease-associated arthritis, and psoriatic arthritis. Genetically, these disease processes have been linked by the presence of HLA-B27. They manifest with axial and peripheral symptoms, such as inflammatory back pain, enthesitis, oligoarthritis, and dactylitis. The onset of symptoms can begin before the age of 45; however, because of the wide range of signs and symptoms, diagnosis can be delayed, leading to unchecked inflammation, structural damage, and later, restriction in physical mobility.
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25
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Zeng-Wang YM, Cares K, Thomas R, El-Baba M. The Effectiveness of Methylprednisolone as a Premedication Among the Pediatric Population for Preventing Infusion-Related Reactions to Infliximab. Gastroenterol Nurs 2021; 44:449-454. [PMID: 34690297 DOI: 10.1097/sga.0000000000000592] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Accepted: 01/13/2021] [Indexed: 11/25/2022] Open
Abstract
Administering medications prior to infliximab infusions to prevent infusion-related infliximab reactions is a common practice in the United States. However, the premedication protocol varies among different institutions. The purpose of this study was to demonstrate whether the use of methylprednisolone was effective as a premedication to prevent infusion reactions while infliximab was administered to children with inflammatory bowel disease. The effect of concurrent use of other immunomodulators on the rate of reaction incidents was also studied. This was a retrospective chart review, assessing children younger than 21 years diagnosed with inflammatory bowel disease from January 2008 to April 2018. The incident rate of infusion reactions was also compared between two cohorts: those who received the premedication of methylprednisolone and those who did not. Subgroup analysis of concomitant immunomodulators, infliximab dose and frequency, and anti-infliximab assay were also performed. A total of 34 subjects received methylprednisolone as a premedication and 151 subjects did not. No statistically significant difference of allergic reactions was found between the two groups (p = .727). Concomitant immunomodulator therapy lowered the likelihood of developing reactions (p = .048). This study was conducted to help pediatric gastroenterology and infusion nurses better understand and implement evidence-based approaches in the premedication protocol for infusions of anti-tumor necrosis factor-α (anti-TNF-α) antibody products.
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Affiliation(s)
- Yiping Maggie Zeng-Wang
- Yiping Maggie Zeng-Wang, MSN, FNP-BC, is Nurse Practitioner, Children's Hospital of Michigan, Detroit Medical Center, Detroit
- Kristen Cares, MD, is Pediatrician/Assistant Professor, Children's Hospital of Michigan, Detroit Medical Center, Detroit
- Ronald Thomas, PhD, is Statistician, Children's Hospital of Michigan, Detroit Medical Center, Detroit
- Mohammad El-Baba, MD, is Pediatrician/Professor, Children's Hospital of Michigan, Detroit Medical Center, Detroit
| | - Kristen Cares
- Yiping Maggie Zeng-Wang, MSN, FNP-BC, is Nurse Practitioner, Children's Hospital of Michigan, Detroit Medical Center, Detroit
- Kristen Cares, MD, is Pediatrician/Assistant Professor, Children's Hospital of Michigan, Detroit Medical Center, Detroit
- Ronald Thomas, PhD, is Statistician, Children's Hospital of Michigan, Detroit Medical Center, Detroit
- Mohammad El-Baba, MD, is Pediatrician/Professor, Children's Hospital of Michigan, Detroit Medical Center, Detroit
| | - Ronald Thomas
- Yiping Maggie Zeng-Wang, MSN, FNP-BC, is Nurse Practitioner, Children's Hospital of Michigan, Detroit Medical Center, Detroit
- Kristen Cares, MD, is Pediatrician/Assistant Professor, Children's Hospital of Michigan, Detroit Medical Center, Detroit
- Ronald Thomas, PhD, is Statistician, Children's Hospital of Michigan, Detroit Medical Center, Detroit
- Mohammad El-Baba, MD, is Pediatrician/Professor, Children's Hospital of Michigan, Detroit Medical Center, Detroit
| | - Mohammad El-Baba
- Yiping Maggie Zeng-Wang, MSN, FNP-BC, is Nurse Practitioner, Children's Hospital of Michigan, Detroit Medical Center, Detroit
- Kristen Cares, MD, is Pediatrician/Assistant Professor, Children's Hospital of Michigan, Detroit Medical Center, Detroit
- Ronald Thomas, PhD, is Statistician, Children's Hospital of Michigan, Detroit Medical Center, Detroit
- Mohammad El-Baba, MD, is Pediatrician/Professor, Children's Hospital of Michigan, Detroit Medical Center, Detroit
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26
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A Practical Guide to Therapeutic Drug Monitoring of Biologic Medications for Inflammatory Bowel Disease. J Clin Med 2021; 10:jcm10214990. [PMID: 34768509 PMCID: PMC8584740 DOI: 10.3390/jcm10214990] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2021] [Revised: 10/19/2021] [Accepted: 10/20/2021] [Indexed: 02/07/2023] Open
Abstract
Therapeutic drug monitoring (TDM) is a useful strategy to optimize biologic medications for inflammatory bowel disease not responsive to standard dosing regimens. TDM is cost effective for anti-tumor necrosis factor agents in the setting of loss of response (reactive TDM). Optimizing drug dosing when patients are in remission (proactive TDM) may be beneficial in certain circumstances. However, frequently the serum drug concentration in isolation becomes the focus TDM. Additionally, the lines of reactive and proactive TDM can quickly blur in many common clinical settings. Physicians employing a TDM based strategy need to place the drug concentration in context with the inflammatory status of the patient, the underlying pharmacokinetics and pharmacodynamics of the drug, the risk of immunogenicity, and the therapeutic goals for the patient. Physicians should understand the limits of TDM and feel comfortable making therapeutic decisions with imperfect information. The goal of this narrative review is to provide a framework of questions that physicians can use to employ TDM effectively in practice.
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27
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Larussa T, Basile A, Palleria C, Iannelli C, Vero A, Giubilei L, De Sarro C, Suraci E, Marasco R, Imeneo M, Russo E, Abenavoli L, De Sarro G, Luzza F. Real-life burden of adverse reactions to biological therapy in inflammatory bowel disease: a single-centre prospective case series. Med Pharm Rep 2021; 94:289-297. [PMID: 34430850 DOI: 10.15386/mpr-1897] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2020] [Revised: 02/20/2021] [Accepted: 03/15/2021] [Indexed: 12/13/2022] Open
Abstract
Background/aim Biologics represent a key therapeutic option in inflammatory bowel disease (IBD), but are associated with several side effects. Post-marketing surveillance, through a spontaneous adverse drug reactions (ADRs) monitoring system, is essential to assess the safety profile of biologics. The aim of the study was to prospectively evaluate the occurrence of ADRs in IBD patients treated with biologics from a single centre in Southern Italy. Methods Data from patients with Crohn's Disease (CD) and Ulcerative Colitis (UC) who underwent biological therapy were prospectively collected. ADRs were classified according to the Medical Dictionary for Regulatory Activities (MedDRA®). Results Overall, 68 (54% male, 68% with UC and 32% with CD) biologic-naïve IBD patients underwent biological therapy. Mean follow-up was 11.7 ± 6.2 months. As a results of switches, for 68 patients we obtained 96 biologic prescriptions. Overall, 45 ADRs occurred in 36 (53%) patients, distributed as follows (ADRs/prescriptions): 19/37 with IFX-Remicade, 5/12 with IFX-Remsima, 8/9 with GOL, 11/26 with ADA, and 2/12 with VDZ. Mild ADRs were 29 (64%), moderate 15 (34%) and 1 (2%) severe. General disorders and administration related reactions were the most frequent ADRs (35%), followed by skin and subcutaneous tissue disorders (20%), infections (15%), musculoskeletal (11%), respiratory (6%) blood (4%), gastrointestinal (4%), and vascular disorders (2%). In 9 cases (20%) the ADRs resulted in definitive discontinuation of biologic therapy. Conclusion In a prospective cohort of IBD patients, more than half experienced ADRs during biologic therapy. General disorders and administration related reactions were the most common ADRs, while infections were less common and rarely led to discontinuation of therapy. Findings underline the importance of surveillance in management of IBD patients during biologic therapy and implementing safety protocols with data from real-life settings.
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Affiliation(s)
- Tiziana Larussa
- Department of Health Sciences, University "Magna Græcia" of Catanzaro, Italy
| | - Antonio Basile
- Department of Health Sciences, University "Magna Græcia" of Catanzaro, Italy
| | - Caterina Palleria
- Department of Health Sciences, University "Magna Græcia" of Catanzaro, Italy
| | - Chiara Iannelli
- Department of Health Sciences, University "Magna Græcia" of Catanzaro, Italy
| | - Ada Vero
- Department of Health Sciences, University "Magna Græcia" of Catanzaro, Italy
| | - Lidia Giubilei
- Department of Health Sciences, University "Magna Græcia" of Catanzaro, Italy
| | - Caterina De Sarro
- Department of Health Sciences, University "Magna Græcia" of Catanzaro, Italy
| | - Evelina Suraci
- Department of Health Sciences, University "Magna Græcia" of Catanzaro, Italy
| | - Raffaella Marasco
- Department of Health Sciences, University "Magna Græcia" of Catanzaro, Italy
| | - Maria Imeneo
- Department of Health Sciences, University "Magna Græcia" of Catanzaro, Italy
| | - Emilio Russo
- Department of Health Sciences, University "Magna Græcia" of Catanzaro, Italy
| | - Ludovico Abenavoli
- Department of Health Sciences, University "Magna Græcia" of Catanzaro, Italy
| | | | - Francesco Luzza
- Department of Health Sciences, University "Magna Græcia" of Catanzaro, Italy
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Rong JM, Luo J, Huang Q, Miao YL. Individualized selection of biological agents in treatment of inflammatory bowel disease. Shijie Huaren Xiaohua Zazhi 2021; 29:893-900. [DOI: 10.11569/wcjd.v29.i15.893] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic non-specific inflammatory disease that can affect the ileum, colon, rectum, and even the entire digestive tract. In recent 10 years, with the in-depth understanding of its pathological mechanisms, the development of new drugs has been accelerated, and more and more biological agents have begun to be widely used in the treatment of IBD. The emergence of biological agents has significance for the treatment of IBD. This article will discuss how to individualize the selection of biologics from three aspects: The mechanism of action and clinical application of different biological agents, risk weighing, and rescue treatment for failure of anti-TNF therapy.
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Affiliation(s)
- Jia-Mei Rong
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan Province, China
| | - Juan Luo
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan Province, China
| | - Qi Huang
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan Province, China
| | - Ying-Lei Miao
- Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan Province, China
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Waldron JL, Schworer SA, Kwan M. Hypersensitivity and Immune-related Adverse Events in Biologic Therapy. Clin Rev Allergy Immunol 2021; 62:413-431. [PMID: 34319562 DOI: 10.1007/s12016-021-08879-w] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/13/2021] [Indexed: 12/13/2022]
Abstract
Biologic medications are an expanding field of therapeutics for various medical conditions including cancer and inflammatory diseases. Due to their targeted approach to therapy, biologics can be less toxic than traditional systemic medications. However, as use becomes more widespread, adverse effects from biologic administration have also become apparent. Immune-related adverse events are a common mechanism by which biologics can cause on-target immune-related toxicities and both immediate and delayed-type hypersensitivity reactions. Immediate hypersensitivity reactions can be mediated by cytokine release or antibody mediated reactions, while delayed-type hypersensitivity is most often caused by serum sickness-like reactions. Additionally, biologics used for treatment of cancer using checkpoint blockade and rheumatologic disease using cytokine blockade can result in autoimmunity. Finally, when inflammatory cytokines are targeted for treatment of autoimmune or autoinflammatory disease, the host immune defense can be compromised predisposing to secondary immunodeficiency. This review will discuss the mechanisms of these reactions and discuss examples of biologics implicated in each of these adverse events.
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Affiliation(s)
- Jamie L Waldron
- Department of Medicine, Division of Rheumatology, Allergy, and Immunology, UNC School of Medicine, Chapel Hill, NC, USA
| | - Stephen A Schworer
- Department of Pediatrics, Division of Allergy & Immunology, UNC School of Medicine, Chapel Hill, NC, USA
| | - Mildred Kwan
- Department of Medicine, Division of Rheumatology, Allergy, and Immunology, UNC School of Medicine, Chapel Hill, NC, USA.
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Premedication Does Not Influence the Incidence of Infliximab Infusion Reactions in Pediatric Patients with Inflammatory Bowel Disease-A Single Center Case-Control Study. J Clin Med 2021; 10:jcm10143177. [PMID: 34300342 PMCID: PMC8303466 DOI: 10.3390/jcm10143177] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/15/2021] [Revised: 07/14/2021] [Accepted: 07/15/2021] [Indexed: 12/15/2022] Open
Abstract
Background: Infusion reactions (IRs) are the most common adverse events (AEs) of infliximab (IFX) treatment in patients with inflammatory bowel disease (IBD). Prophylactic premedication (PM) with corticosteroids or antihistamines prior to IFX infusions has been used in clinical practice, but its efficacy is not known. The aim of this study was to assess the influence of steroid PM on IR incidence in pediatric patients with IBD receiving IFX. Methods: We performed a case–control study that included pediatric patients with IBD receiving IFX. Patients were divided into four subgroups according to the agent and PM they received: Remicade (original drug) + PM, and two biosimilars—Reshma +/− PM, and Flixabi—PM. At our site, until 2018, PM with steroids was used as a part of standard IFX infusion (PM+); however, since then, this method has no longer been administered (PM−). IRs were divided into mild/severe reactions. Differences between subgroups were assessed with the appropriate chi-square test. Multivariate logistic regression was used to assess associations between PM and IR incidence, correcting for co-medication usage. Results: There were 105 children (55 PM+, 44 male, mean age 15 years) included in the study who received 1276 infusions. There was no difference between the PM+ and PM− subgroups, either in incidence of IR (18.2% vs. 16.0% of patients, p > 0.05) or in percentage of infusions followed by IR (2.02% vs. 1.02% of infusions, p > 0.5). The OR of developing IR when using PM was 0.34, and the difference in IRs ratio in PM+ and PM− patients was not statistically significant (95% CI, 0.034–1.9). There were 11/18 (61.1%) severe IRs (anaphylactic shock) reported in all patients (both PM+ and PM−). Conclusion: At our site, the incidence of IR was low, and PM did not decrease the incidence of IR in pediatric patients with IBD receiving IFX. These results indicate that PM with steroids should not be a standard part of IFX infusion to prevent IR.
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Baker MC, Weng Y, Fairchild R, Ahuja N, Rohatgi N. Comparison of Adverse Events Among Home- vs Facility-Administered Biologic Infusions, 2007-2017. JAMA Netw Open 2021; 4:e2110268. [PMID: 34081140 PMCID: PMC8176330 DOI: 10.1001/jamanetworkopen.2021.10268] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022] Open
Abstract
IMPORTANCE Infusion reactions occur in 7% to 20% of patients receiving biologics. Home infusions are convenient and incur lower costs but may be associated with more adverse events; the safety of receiving biologic infusions for immune-mediated diseases at home remains unclear. OBJECTIVE To assess whether patients receiving home biologic infusions have increased adverse events requiring emergency department (ED) or hospital admission compared with patients receiving facility infusions. DESIGN, SETTING, AND PARTICIPANTS This retrospective cohort study used administrative claims data from a large national insurer for adult patients who received biologic infusions for immune-mediated disease between January 2007 and December 2017. Patients with hematologic malignant neoplasms or bone marrow transplantation were excluded. Data were analyzed from August 2019 to October 2020. MAIN OUTCOMES AND MEASURES ED or hospital admission on the same or next day after administration of a biologic infusion at home vs at a facility; secondary outcomes included discontinuation of the biologic after an ED or hospital admission and postinfusion mortality. RESULTS Of a total of 57 220 patients (mean [SD] age, 50.1 [14.8] years; 512 314 [68.1%] women) who received 752 150 biologic infusions (34 078 home infusions [4.5%] to 3954 patients and 718 072 facility infusions [95.5%] to 54 770 patients), patients who received home infusions were younger (mean [SD] age, 43.2 [13.2] vs 51.3 [14.8] years), more likely to be men (14 031 [41.2%] vs 225 668 [31.4%]), and had a lower Charlson comorbidity score compared with patients who received facility infusions (mean [SD] score, 0.5 [1.0] vs 1.1 [1.3]). Home infusions were associated with 25% increased odds of ED or hospital admission on the same or next day after the infusion (odds ratio [OR], 1.25; 95% CI, 1.09-1.44; P = .002) and 28% increased odds of discontinuation of the biologic after the ED or hospital admission (OR, 1.28; 95% CI, 1.08-1.51; P = .005). There was no difference in postinfusion mortality between home or facility infusions. The rates of adverse events were highest with home infusions of tocilizumab (48 of 481 infusions [10.0%]), vedolizumab (150 of 2681 infusions [5.6%]), and infliximab (1085 of 20 653 infusions [5.3%]), although the number of tocilizumab and vedolizumab infusions was low. CONCLUSIONS AND RELEVANCE In this study, biologic infusions administered at home, compared with those administered at a facility, were associated with increased adverse events requiring escalation of care. Because the number of home infusions has increased and is expected to continue to rise, the safety implications of administering biologic infusions at home needs to be further assessed.
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Affiliation(s)
- Matthew C. Baker
- Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, California
| | - Yingjie Weng
- Quantitative Sciences Unit, Division of Biomedical Informatics Research, Department of Medicine, Stanford University, Stanford, California
| | - Robert Fairchild
- Division of Immunology and Rheumatology, Department of Medicine, Stanford University, Stanford, California
| | - Neera Ahuja
- Division of Hospital Medicine, Department of Medicine, Stanford University, Stanford, California
| | - Nidhi Rohatgi
- Division of Hospital Medicine, Department of Medicine, Stanford University, Stanford, California
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Li Q, Ding X, Liu Y, Marcella C, Dai M, Zhang T, Bai J, Xiang L, Wen Q, Cui B, Zhang F. Fecal Microbiota Transplantation is a Promising Switch Therapy for Patients with Prior Failure of Infliximab in Crohn's Disease. Front Pharmacol 2021; 12:658087. [PMID: 34079458 PMCID: PMC8166050 DOI: 10.3389/fphar.2021.658087] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/25/2021] [Accepted: 05/04/2021] [Indexed: 12/12/2022] Open
Abstract
Background: How to handle patients with anti-tumor necrosis factor (anti-TNF) failure was a common challenge to clinicians in Crohn's disease (CD). The present study is dedicated to clarifying whether fecal microbiota transplantation (FMT) could be a switch therapy for patients with prior failure of infiiximab (IFX) in CD in a long-term observation. Methods: Thirty-six patients with CD who had prior failure of IFX were recruited from January 2013 to December 2019. The "one-hour FMT protocol" was followed in all patients. All patients received the first course of FMT through gastroscopy or mid-gut transendoscopic enteral tubing. After April 2014, the methodology of FMT was coined as washed microbiota transplantation (WMT), substituting for the manual methods, which is dependent on the automatic microbiota purification system and the washing process. The primary endpoint of this study was the clinical remission at one month and one year after FMT. The secondary endpoint was the safety of FMT in the short and long term, and clinical factors as predictors for long-term efficacy of FMT. Clinical factors as independent predictors of efficacy from FMT were isolated using univariable and multivariable logistic regression analysis. Results: There was no significant difference in the rates of clinical response and remission between IFX treatment stage and FMT treatment stage (at one month, three months and six months after administration) (p > 0.05). Compared with those of 19 patients who achieved clinical remission at one month after FMT, the rates of clinical relapse were significantly higher in 18 patients who achieved clinical remission at one month after IFX [log-rank test p = 0.0009 HR = 3.081 (95% CI 1.43-6.639)]. Multivariate analysis revealed that the gender of donor (95% CI: 0.001-0.72; p = 0.031) was an independent predictor of efficacy at one year after FMT. No serious adverse events (AEs) associated with FMT were observed during and after FMT. The rate of AEs was significantly lower in group FMT than that in group IFX (p = 0.002). Conclusion: The present findings first time provided the evidence for clinicians to consider FMT into practice as an alternative switch therapy for patients with prior loss of response or intolerance to IFX in CD. Clinical Trial Registration: https://clinicaltrials.gov, identifier NCT01793831.
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Affiliation(s)
- Qianqian Li
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xiao Ding
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
| | - Yujie Liu
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Cicilia Marcella
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Min Dai
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Ting Zhang
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jianling Bai
- Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China
| | - Liyuan Xiang
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Quan Wen
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Bota Cui
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Key Lab of Holistic Integrative Enterology, Nanjing Medical University, Nanjing, China
| | - Faming Zhang
- Medical Center for Digestive Diseases, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Department of Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, China
- National Clinical Research Center for Digestive Diseases, Xi’an, China
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Broyles AD, Banerji A, Barmettler S, Biggs CM, Blumenthal K, Brennan PJ, Breslow RG, Brockow K, Buchheit KM, Cahill KN, Cernadas J, Chiriac AM, Crestani E, Demoly P, Dewachter P, Dilley M, Farmer JR, Foer D, Fried AJ, Garon SL, Giannetti MP, Hepner DL, Hong DI, Hsu JT, Kothari PH, Kyin T, Lax T, Lee MJ, Lee-Sarwar K, Liu A, Logsdon S, Louisias M, MacGinnitie A, Maciag M, Minnicozzi S, Norton AE, Otani IM, Park M, Patil S, Phillips EJ, Picard M, Platt CD, Rachid R, Rodriguez T, Romano A, Stone CA, Torres MJ, Verdú M, Wang AL, Wickner P, Wolfson AR, Wong JT, Yee C, Zhou J, Castells M. Practical Guidance for the Evaluation and Management of Drug Hypersensitivity: Specific Drugs. THE JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY-IN PRACTICE 2021; 8:S16-S116. [PMID: 33039007 DOI: 10.1016/j.jaip.2020.08.006] [Citation(s) in RCA: 121] [Impact Index Per Article: 30.3] [Reference Citation Analysis] [Subscribe] [Scholar Register] [Received: 08/10/2020] [Accepted: 08/10/2020] [Indexed: 02/06/2023]
Affiliation(s)
- Ana Dioun Broyles
- Division of Allergy/Immunology, Boston Children's Hospital, Boston, Mass
| | - Aleena Banerji
- Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, Mass
| | - Sara Barmettler
- Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, Mass
| | - Catherine M Biggs
- Department of Pediatrics, British Columbia Children's Hospital, University of British Columbia, Vancouver, Canada
| | - Kimberly Blumenthal
- Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, Mass
| | - Patrick J Brennan
- Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Boston, Mass
| | - Rebecca G Breslow
- Division of Sports Medicine, Brigham and Women's Hospital, Boston, Mass
| | - Knut Brockow
- Department of Dermatology and Allergy Biederstein, School of Medicine, Technical University of Munich, Munich, Germany
| | - Kathleen M Buchheit
- Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Boston, Mass
| | - Katherine N Cahill
- Division of Allergy, Pulmonary and Critical Care Medicine, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tenn
| | - Josefina Cernadas
- Allergology and Immunology Service, Centro Hospitalar Universitário de S.João Hospital, Porto, Portugal
| | - Anca Mirela Chiriac
- Division of Allergy, Department of Pulmonology, Hôpital Arnaud de Villeneuve, University Hospital of Montpellier, Montpellier, France
| | - Elena Crestani
- Division of Allergy/Immunology, Boston Children's Hospital, Boston, Mass
| | - Pascal Demoly
- Division of Allergy, Department of Pulmonology, Hôpital Arnaud de Villeneuve, University Hospital of Montpellier, Montpellier, France
| | - Pascale Dewachter
- Department of Anesthesiology and Intensive Care Medicine, Groupe Hospitalier Paris-Seine-Saint-Denis, Assistance Publique-Hôpitaux de Paris, Paris, France
| | - Meredith Dilley
- Division of Allergy/Immunology, Boston Children's Hospital, Boston, Mass
| | - Jocelyn R Farmer
- Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, Mass
| | - Dinah Foer
- Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Boston, Mass
| | - Ari J Fried
- Division of Allergy/Immunology, Boston Children's Hospital, Boston, Mass
| | - Sarah L Garon
- Associated Allergists and Asthma Specialists, Chicago, Ill
| | - Matthew P Giannetti
- Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Boston, Mass
| | - David L Hepner
- Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Boston, Mass
| | - David I Hong
- Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Boston, Mass
| | - Joyce T Hsu
- Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Boston, Mass
| | - Parul H Kothari
- Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Boston, Mass
| | - Timothy Kyin
- Division of Asthma, Allergy & Immunology, University of Virginia, Charlottesville, Va
| | - Timothy Lax
- Division of Allergy and Inflammation, Beth Israel Deaconess Medical Center, Boston, Mass
| | - Min Jung Lee
- Allergy and Immunology at Hoag Medical Group, Newport Beach, Calif
| | - Kathleen Lee-Sarwar
- Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Mass
| | - Anne Liu
- Division of Allergy / Immunology, Stanford University School of Medicine, Palo Alto, Calif
| | - Stephanie Logsdon
- Division of Allergy and Immunology, Department of Pediatrics, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio
| | - Margee Louisias
- Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Boston, Mass
| | - Andrew MacGinnitie
- Division of Allergy/Immunology, Boston Children's Hospital, Boston, Mass
| | - Michelle Maciag
- Division of Allergy/Immunology, Boston Children's Hospital, Boston, Mass
| | - Samantha Minnicozzi
- Division of Allergy and Clinical Immunology, Respiratory Medicine, Department of Pediatrics, University of Virginia, Charlottesville, Va
| | - Allison E Norton
- Division of Allergy, Immunology and Pulmonology, Monroe Carell Jr. Children's Hospital at Vanderbilt, Nashville, Tenn
| | - Iris M Otani
- Division of Pulmonary, Critical Care, Allergy, and Sleep, Department of Medicine, University of California, San Francisco Medical Center, San Francisco, Calif
| | - Miguel Park
- Division of Allergic Diseases, Mayo Clinic, Rochester, Minn
| | - Sarita Patil
- Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, Mass
| | - Elizabeth J Phillips
- Department of Medicine & Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tenn
| | - Matthieu Picard
- Division of Allergy and Clinical Immunology, Department of Medicine, Hôpital Maisonneuve-Rosemont, Université de Montréal, Montréal, Québec, Canada
| | - Craig D Platt
- Division of Immunology, Boston Children's Hospital, Boston, Mass
| | - Rima Rachid
- Division of Immunology, Boston Children's Hospital, Boston, Mass
| | - Tito Rodriguez
- Drug Allergy Department, Al-Rashed Allergy Center, Sulaibikhat, Al-Kuwait, Kuwait
| | - Antonino Romano
- IRCCS Oasi Maria S.S., Troina, Italy & Fondazione Mediterranea G.B. Morgagni, Catania, Italy
| | - Cosby A Stone
- Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, Nashville, Tenn
| | - Maria Jose Torres
- Allergy Unit and Research Group, Hospital Regional Universitario de Málaga, UMA-IBIMA-BIONAND, ARADyAL, Málaga, Spain
| | - Miriam Verdú
- Allergy Unit, Hospital Universitario de Ceuta, Ceuta, Spain
| | - Alberta L Wang
- Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Boston, Mass
| | - Paige Wickner
- Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Boston, Mass
| | - Anna R Wolfson
- Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, Mass
| | - Johnson T Wong
- Division of Rheumatology, Allergy and Immunology, Massachusetts General Hospital, Boston, Mass
| | - Christina Yee
- Division of Immunology, Boston Children's Hospital, Boston, Mass
| | - Joseph Zhou
- Division of Allergy/Immunology, Boston Children's Hospital, Boston, Mass
| | - Mariana Castells
- Drug hypersensitivity and Desensitization Center, Brigham and Women's Hospital, Boston, Mass
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Holcomb ZE, Porter ML, Kimball AB. A safety review of biologic therapies for the management of hidradenitis suppurativa and unmet needs. Expert Opin Drug Saf 2021; 20:1147-1161. [PMID: 33910441 DOI: 10.1080/14740338.2021.1924147] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022]
Abstract
INTRODUCTION Hidradenitis suppurativa (HS) is a chronic, debilitating inflammatory skin disorder characterized by nodules, abscesses, fistulae, and significant scarring in intertriginous areas rich in apocrine glands. Immunomodulator drugs, including biologics, are a mainstay of treatment for this disease. AREAS COVERED This review details the safety profiles of various biologic therapies currently available commercially that have been tried for HS as assessed in clinical trials and observational studies. As the only Food and Drug Administration (FDA)-approved medication for the treatment of moderate-to-severe HS, adalimumab is discussed in the most detail. Additional biologic medications, including tumor necrosis factor α (TNFα) inhibitors, interleukin 1 (IL-1) inhibitors, IL-12 and IL-23 inhibitors, IL-17 inhibitors, and IL-23 inhibitors, are discussed as well. Safety concerns in special populations, including pregnant women and children, are outlined. EXPERT OPINION Existing data support excellent short-term and long-term safety profiles for adalimumab, although caution must be taken with use in high-risk patient populations, including those with chronic infections or increased risk of malignancy. Based on their safety data for other indications, additional biologic agents appear safe in HS as well. However, further research is needed to fully understand the safety profiles of these medications in the HS population.
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Affiliation(s)
- Zachary E Holcomb
- Department of Dermatology, Massachusetts General Hospital, Harvard Combined Dermatology Residency Program, Boston, MA, USA
| | - Martina L Porter
- Clinical Laboratory for Epidemiology and Applied Research in Skin (CLEARS), Department of Dermatology, Beth Israel Deaconess Medical Center, Boston, MA, USA.,Department of Dermatology, Harvard Medical School, Boston, MA, USA
| | - Alexa B Kimball
- Clinical Laboratory for Epidemiology and Applied Research in Skin (CLEARS), Department of Dermatology, Beth Israel Deaconess Medical Center, Boston, MA, USA.,Department of Dermatology, Harvard Medical School, Boston, MA, USA
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Tran-Minh ML, Gornet JM, Maillet M, Houze P, Simon M, McLellan P, Hassid D, Vivier-Chicoteau J, Baudry C, Hammoudi N, Allez M. Safety of Hydrocortisone Premedication Discontinuation in Patients with Inflammatory Bowel Disease on Maintenance Therapy with Infliximab: a Prospective Clinical and Pharmacological Study. J Crohns Colitis 2021; 15:742-748. [PMID: 33205193 DOI: 10.1093/ecco-jcc/jjaa231] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND Hydrocortisone premedication reduces the risk of antibodies to infliximab [ATIs] formation in patients receiving infliximab [IFX] therapy for inflammatory bowel disease [IBD]. AIM We aimed to determine the safety of hydrocortisone premedication withdrawal in IBD patients with sustained clinical response on maintenance therapy with IFX. METHODS We performed an observational prospective pharmacoclinical study in a tertiary referral centre, including all consecutive IBD outpatients with no previous IFX infusion reaction and in clinical remission on maintenance IFX [alone or in combination therapy] for at least 6 months. This cohort was followed for 1 year after discontinuation of hydrocortisone premedication. RESULTS Among the 268 IBD outpatients, 95 patients met the inclusion criteria [mean age 38 years; 64% male; 80% Crohn's disease; 45% combination therapy]. The median IFX duration was 5 years [0.54-14] with a mean infused dose of 533 mg [200-1000] and a mean interval duration of 7.9 weeks [4-10]. None of the patients developed permanent ATIs or infusion-related reaction at 1 year. Four patients developed transient ATIs without loss of clinical response. There was no significant variation of infliximab serum trough levels [5.5 µg/mL vs 5.9 µg/mL] measured at the time of the three IFX infusions before and after hydrocortisone withdrawal. Loss of response rate to IFX was 18% at 1 year. CONCLUSIONS Hydrocortisone discontinuation is safe in IBD patients with sustained clinical remission on maintenance therapy with IFX. Our data suggest that routine premedication with hydrocortisone is unnecessary in patients in prolonged remission under IFX maintenance therapy.
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Affiliation(s)
- My-Linh Tran-Minh
- Service de Gastroentérologie, Université de Paris, APHP, Hôpital Saint-Louis, Paris, France
| | - Jean-Marc Gornet
- Service de Gastroentérologie, Université de Paris, APHP, Hôpital Saint-Louis, Paris, France
| | - Marianne Maillet
- Service de Gastroentérologie, Université de Paris, APHP, Hôpital Saint-Louis, Paris, France
| | - Pascal Houze
- Service de Biochimie, Université de Paris, APHP, Hôpital Necker, Paris, France
| | - Marion Simon
- Service de Gastroentérologie, Institut Mutualiste Montsouris, Paris, France
| | - Paul McLellan
- Service de Gastroentérologie, Université de Paris, APHP, Hôpital Saint-Louis, Paris, France
| | - Deborah Hassid
- Service de Gastroentérologie, Université de Paris, APHP, Hôpital Saint-Louis, Paris, France
| | | | - Clotilde Baudry
- Service de Gastroentérologie, Université de Paris, APHP, Hôpital Saint-Louis, Paris, France
| | - Nassim Hammoudi
- Service de Gastroentérologie, Université de Paris, APHP, Hôpital Saint-Louis, Paris, France
| | - Matthieu Allez
- Service de Gastroentérologie, Université de Paris, APHP, Hôpital Saint-Louis, Paris, France
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Nuñez F P, Quera R, Simian D, Flores L, Figueroa C, Ibañez P, Kronberg U, Lubascher J, Pizarro G. Infliximab in inflammatory bowel disease. Is premedication necessary? GASTROENTEROLOGIA Y HEPATOLOGIA 2021; 44:321-329. [PMID: 33386199 DOI: 10.1016/j.gastrohep.2020.07.018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/24/2020] [Revised: 07/08/2020] [Accepted: 07/13/2020] [Indexed: 12/28/2022]
Abstract
BACKGROUND The use of infliximab (IFX) in inflammatory bowel disease (IBD) has been associated with a 1-6% risk of infusion reactions. The usefulness of premedication with corticosteroids, paracetamol and /or antihistamines is controversial. AIM The aim of this study is to assess, in IBD patients on IFX, whether there are differences in secondary reactions to the infusion between those who use premedication or not. METHODS A retrospective cohort study was performed identifying patients with a diagnosis of IBD who received IFX at our institution between January 2009 and July 2019. Acute reactions were defined as those that occurred in the first 24 hours postinfusion and late reactions for more than 24 hours. Infusion reactions were classified as mild, moderate and severe. Descriptive and association statistics were used (χ2; p < 0.05). RESULTS Sixty-four patients were included with 1,263 infusions in total, 52% men. Median infusions per patient was 22 (2-66). All induction infusions were administered with premedication, and in maintenance in 57% of them. Premedication was given with hydrocortisone, chlorphenamine and paracetamol. Most of reactions were acute, mild or moderate in severity and no patient needed to discontinue IFX. In the maintenance group, there were 9/718 (1.2%) infusion reactions with premedication and 4/358 (1.1%) without it (p = 0.606). In the induction group, there were 8/187 (4.3%) infusion reactions, significantly higher when compared with both maintenance groups. CONCLUSIONS In this group, premedication use during maintenance was not effective at reducing the rate of infusion reactions. These results suggest that premedication would not be necessary.
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Affiliation(s)
- Paulina Nuñez F
- Programa Enfermedad Inflamatoria Intestinal, Departamento Gastroenterología, Hospital San Juan de Dios Hospital, Universidad de Chile, Santiago, Chile
| | | | | | - Lilian Flores
- Programa Enfermedad Inflamatoria Intestinal, Departamento Gastroenterología, Hospital San Juan de Dios Hospital, Universidad de Chile, Santiago, Chile
| | - Carolina Figueroa
- Programa Enfermedad Inflamatoria Intestinal, Departamento Gastroenterología, Hospital San Juan de Dios Hospital, Universidad de Chile, Santiago, Chile
| | - Patricio Ibañez
- Programa Enfermedad Inflamatoria Intestinal, Departamento Gastroenterología, Hospital San Juan de Dios Hospital, Universidad de Chile, Santiago, Chile
| | - Udo Kronberg
- Unidad de Coloproctología, Departamento de Cirugía, Clínica Las Condes, Santiago, Chile
| | - Jaime Lubascher
- Programa Enfermedad Inflamatoria Intestinal, Departamento Gastroenterología, Hospital San Juan de Dios Hospital, Universidad de Chile, Santiago, Chile
| | - Gonzalo Pizarro
- Programa Enfermedad Inflamatoria Intestinal, Departamento Gastroenterología, Hospital San Juan de Dios Hospital, Universidad de Chile, Santiago, Chile
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Wen S, Unuma K, Chinuki Y, Hikino H, Uemura K. Fatal anaphylaxis due to alpha-gal syndrome after initial cetuximab administration: The first forensic case report. Leg Med (Tokyo) 2021; 51:101878. [PMID: 33892262 DOI: 10.1016/j.legalmed.2021.101878] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2021] [Revised: 03/27/2021] [Accepted: 03/31/2021] [Indexed: 10/21/2022]
Abstract
Cetuximab is mainly used for the treatment of advanced and metastatic colorectal cancer. Owing to the oligosaccharide galactose-α-1,3-galactose (α-gal) in its heavy chain, cetuximab can induce severe IgE-dependent anaphylaxis. α-Gal is also the antigen responsible for α-gal syndrome, known as mammalian meat allergy. Patients with α-gal syndrome may suffer from cetuximab-induced anaphylaxis at the first administration because of developed α-gal-specific IgE antibodies. A male patient in his 50 s with metastatic colon cancer was receiving chemotherapy involving scheduled cetuximab administration. However, he died soon after the first administration. Forensic autopsy confirmed rectal cancer, metastatic rectal cancer in the liver, and renal cancer. Laboratory blood tests revealed the presence of cetuximab- and beef-specific IgE antibodies before cetuximab administration and an extremely high level of tryptase after administration. Thus, we determined that the death was caused by cetuximab-induced anaphylaxis due to the preexisting α-gal syndrome. To the best of our knowledge, this is the first autopsy case report in forensic medicine of fatal anaphylaxis after initial cetuximab administration.
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Affiliation(s)
- Shuheng Wen
- Department of Forensic Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan
| | - Kana Unuma
- Department of Forensic Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan.
| | - Yuko Chinuki
- Department of Dermatology, Shimane University, Faculty of Medicine, Shimane, Japan
| | - Hajime Hikino
- Department of Breast Surgery, Matsue Red Cross Hospital, Matsue, Shimane, Japan
| | - Koichi Uemura
- Department of Forensic Medicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Tokyo, Japan
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Cianferoni A. Non-IgE-mediated anaphylaxis. J Allergy Clin Immunol 2021; 147:1123-1131. [PMID: 33832694 DOI: 10.1016/j.jaci.2021.02.012] [Citation(s) in RCA: 63] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/04/2020] [Revised: 02/15/2021] [Accepted: 02/15/2021] [Indexed: 12/17/2022]
Abstract
Anaphylaxis is a rapidly evolving, acute, life-threatening reaction that occurs rapidly on contact with a trigger. Anaphylaxis is classically defined as an allergen-driven process that induces specific IgE and the activation of mast cells and basophils through the cross-linking of IgE receptors. However, it is clear that non-IgE-mediated pathways can induce symptoms indistinguishable from those of classic anaphylaxis, and their activation could explain the severity of IgE-mediated anaphylaxis. Indeed, mast cells and basophils can be activated by antibodies against IgE or their receptors, by molecules such as anaphylatoxins, or through G-coupled receptors. Some other allergens can induce antibodies of class IgG that can activate neutrophils to produce a molecule similar to histamine to induce anaphylaxis. Finally, some inflammatory mediators such as bradykinin or prostaglandin can also modulate mast cell and basophil activation as well as directly cause vasodilation and bronchoconstriction, resulting in anaphylaxis-like reactions.
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Affiliation(s)
- Antonella Cianferoni
- Perelman School of Medicine, University of Pennsylvania, Allergy and Immunology Division, The Children's Hospital of Philadelphia, Philadelphia, Pa.
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39
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Cutaneous Manifestations in Biological-Treated Inflammatory Bowel Disease Patients: A Narrative Review. J Clin Med 2021; 10:jcm10051040. [PMID: 33802483 PMCID: PMC7959457 DOI: 10.3390/jcm10051040] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Revised: 02/12/2021] [Accepted: 02/24/2021] [Indexed: 12/13/2022] Open
Abstract
The biologic era has greatly improved the treatment of Crohn’s disease and ulcerative colitis. Biologics can however induce a wide variety of skin eruptions, especially those targeting the TNF-α and Th17 pathway. These include infusion reactions, eczema, psoriasis, lupus, alopecia areata, vitiligo, lichenoid reactions, granulomatous disorders, vasculitis, skin cancer, and cutaneous infections. It is important to recognize these conditions as treatment-induced adverse reactions and adapt the treatment strategy accordingly. Some conditions can be treated topically while others require cessation or switch of the biological therapy. TNF-α antagonists have the highest rate adverse skin eruptions followed by ustekinumab and anti-integrin receptor blockers. In this review, we provide an overview of the most common skin eruptions which can be encountered in clinical practice when treating IBD (Inflammatory bowel disease) patients and propose a therapeutic approach for each condition.
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40
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Adelman M, Lyons AB, Hamzavi IH. Comment on "High-dose, high-frequency infliximab: A novel treatment paradigm for hidradenitis suppurativa". J Am Acad Dermatol 2020; 84:e201-e202. [PMID: 33253840 DOI: 10.1016/j.jaad.2020.10.095] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/17/2020] [Accepted: 10/02/2020] [Indexed: 01/31/2023]
Affiliation(s)
| | - Alexis B Lyons
- Department of Dermatology, Henry Ford Hospital, Detroit, Michigan
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41
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Solé D, Spindola MAC, Aun MV, Araújo Azi LMTD, Bernd LAG, Garcia DB, Capelo AV, Cumino DDO, Lacerda AE, Lima LC, Morato EF, Nunes RR, Rubini NDPM, da Silva J, Tardelli MA, Watanabe AS, Curi EF, Sano F. [Update on perioperative hypersensitivity reactions: joint document from the Brazilian Society of Anesthesiology (SBA) and Brazilian Association of Allergy and Immunology (ASBAI) - Part II: etiology and diagnosis]. BRAZILIAN JOURNAL OF ANESTHESIOLOGY (ELSEVIER) 2020; 70:642-661. [PMID: 33308829 PMCID: PMC9373683 DOI: 10.1016/j.bjan.2020.08.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/09/2020] [Revised: 07/19/2020] [Accepted: 08/11/2020] [Indexed: 11/30/2022]
Abstract
This second joint document, written by experts from the Brazilian Association of Allergy and Immunology (ASBAI) and Brazilian Society of Anesthesiology (SBA) concerned with perioperative anaphylaxis, aims to review the pathophysiological reaction mechanisms, triggering agents (in adults and children), and the approach for diagnosis during and after an episode of anaphylaxis. As anaphylaxis assessment is extensive, the identification of medications, antiseptics and other substances used at each setting, the comprehensive data documentation, and the use of standardized nomenclature are key points for obtaining more consistent epidemiological information on perioperative anaphylaxis.
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Affiliation(s)
- Dirceu Solé
- Associação Brasileira de Alergia e Imunologia, São Paulo, SP, Brazil; Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo, SP, Brazil
| | - Maria Anita Costa Spindola
- Sociedade Brasileira de Anestesiologia, Rio de Janeiro, RJ, Brazil; Universidade Federal de Santa Catarina, Hospital Universitário Professor Polydoro Ernani de São Thiago, Florianópolis, SC, Brazil
| | - Marcelo Vivolo Aun
- Associação Brasileira de Alergia e Imunologia, São Paulo, SP, Brazil; Faculdade Israelita de Ciências da Saúde Albert Einstein, São Paulo, SP, Brazil; Universidade de São Paulo, Faculdade de Medicina, Hospital Universitário, São Paulo, SP, Brazil
| | - Liana Maria Tôrres de Araújo Azi
- Sociedade Brasileira de Anestesiologia, Rio de Janeiro, RJ, Brazil; Universidade Federal da Bahia, Hospital Universitário Professor Edgard Santos, Salvador, BA, Brasil.
| | - Luiz Antonio Guerra Bernd
- Associação Brasileira de Alergia e Imunologia, São Paulo, SP, Brazil; Fundação Faculdade Federal de Ciências Médicas de Porto Alegre, Porto Alegre, RS, Brazil
| | - Daniela Bianchi Garcia
- Sociedade Brasileira de Anestesiologia, Rio de Janeiro, RJ, Brazil; Hospital Infantil Pequeno Príncipe, Curitiba, PR, Brasil
| | - Albertina Varandas Capelo
- Associação Brasileira de Alergia e Imunologia, São Paulo, SP, Brazil; Universidade Federal do Rio de Janeiro, Hospital Universitário Gaffrée e Guinle, Rio de Janeiro, RJ, Brazil
| | - Débora de Oliveira Cumino
- Sociedade Brasileira de Anestesiologia, Rio de Janeiro, RJ, Brazil; Hospital Infantil Sabará, São Paulo, SP, Brazil
| | - Alex Eustáquio Lacerda
- Associação Brasileira de Alergia e Imunologia, São Paulo, SP, Brazil; Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo, SP, Brazil
| | - Luciana Cavalcanti Lima
- Sociedade Brasileira de Anestesiologia, Rio de Janeiro, RJ, Brazil; Instituto Medicina Integral Prrofessor Fernando Figueira, Recife, PE, Brazil
| | - Edelton Flávio Morato
- Universidade Federal de Santa Catarina, Hospital Universitário Professor Polydoro Ernani de São Thiago, Florianópolis, SC, Brazil
| | - Rogean Rodrigues Nunes
- Sociedade Brasileira de Anestesiologia, Rio de Janeiro, RJ, Brazil; Hospital Geral de Fortaleza (HGF), Departamento de Anestesia, Fortaleza, CE, Brazil
| | - Norma de Paula Motta Rubini
- Associação Brasileira de Alergia e Imunologia, São Paulo, SP, Brazil; Universidade Federal do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brazil
| | - Jane da Silva
- Associação Brasileira de Alergia e Imunologia, São Paulo, SP, Brazil; Universidade Federal de Santa Catarina, Hospital Universitário Professor Polydoro Ernani de São Thiago, Florianópolis, SC, Brazil
| | - Maria Angela Tardelli
- Universidade Federal de São Paulo, Escola Paulista de Medicina, São Paulo, SP, Brazil; Sociedade Brasileira de Anestesiologia, Rio de Janeiro, RJ, Brazil
| | - Alexandra Sayuri Watanabe
- Associação Brasileira de Alergia e Imunologia, São Paulo, SP, Brazil; Universidade de São Paulo, Faculdade de Medicina, Hospital das Clínicas, São Paulo, SP, Brazil
| | - Erick Freitas Curi
- Sociedade Brasileira de Anestesiologia, Rio de Janeiro, RJ, Brazil; Universidade Federal do Espírito Santo, Vitória, ES, Brasil
| | - Flavio Sano
- Associação Brasileira de Alergia e Imunologia, São Paulo, SP, Brazil; Hospital Nipo Brasileiro, São Paulo, SP, Brasil
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Update on perioperative hypersensitivity reactions: joint document from the Brazilian Society of Anesthesiology (SBA) and Brazilian Association of Allergy and Immunology (ASBAI) - Part II: etiology and diagnosis. BRAZILIAN JOURNAL OF ANESTHESIOLOGY (ENGLISH EDITION) 2020. [PMID: 33308829 PMCID: PMC9373683 DOI: 10.1016/j.bjane.2020.10.005] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
This second joint document, written by experts from the Brazilian Association of Allergy and Immunology (ASBAI) and Brazilian Society of Anesthesiology (SBA) concerned with perioperative anaphylaxis, aims to review the pathophysiological reaction mechanisms, triggering agents (in adults and children), and the approach for diagnosis during and after an episode of anaphylaxis. As anaphylaxis assessment is extensive, the identification of medications, antiseptics and other substances used at each setting, the comprehensive data documentation, and the use of standardized nomenclature are key points for obtaining more consistent epidemiological information on perioperative anaphylaxis.
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43
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Eto A, Nakahara T, Furue M. Repeated infliximab injection may shift delayed infusion reactions to acute infusion reactions in patients with psoriasis. J Dermatol 2020; 48:e41-e42. [PMID: 33073412 DOI: 10.1111/1346-8138.15652] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2020] [Revised: 08/25/2020] [Accepted: 09/10/2020] [Indexed: 12/01/2022]
Affiliation(s)
- Ayaka Eto
- Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Takeshi Nakahara
- Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
| | - Masutaka Furue
- Department of Dermatology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan
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44
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Bohra A, Rizvi QAA, Keung CYY, Vasudevan A, van Langenberg DR. Transitioning patients with inflammatory bowel disease from hospital-based to rapid home-based infliximab: A stepwise, safety and patient-orientated process towards sustainability. World J Gastroenterol 2020; 26:5437-5449. [PMID: 33024395 PMCID: PMC7520608 DOI: 10.3748/wjg.v26.i36.5437] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/28/2020] [Revised: 08/10/2020] [Accepted: 09/05/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Infliximab and other intravenous biologic infusions are increasingly used for chronic disorders like inflammatory bowel disease (IBD). Rapid infliximab and home-based infusions are attractive solutions to address resource and capacity issues for infusion centres, yet infliximab infusion reactions reportedly occur in up to 25% of patients with IBD, even at the manufacturers' recommended infusion duration of 2 h. AIM To evaluate the safety, cost and patient satisfaction of transitioning from hospital-based, standard 2 h to rapid home-based, 30-min infliximab infusions. METHODS All patients receiving rapid infliximab infusions for IBD between 2014 to 2017 (39 mo) were compared with those who received standard two-hour IFX infusions between 2005-2013 (96 mo) at a single IBD centre. Data (per-infusion and per-individual) including adverse drug reactions (ADR), duration (based on needle-departure time) and other clinical data were extracted from electronic medical records. Multivariable logistical regression analysis assessed factors potentially associated with increased risk of ADRs to rapid infusions. The primary outcome was the safety [as per relative risk (RR) of ADR] of (1) rapid 30 m infusions (both hospital- and home-based) vs standard 2 h infliximab infusions. Also, relative cost per infusion and patient satisfaction and productivity were evaluated in rapid infusion recipients who transitioned to home-based infusions. RESULTS Of 129 patients who received 1461 rapid IFX infusions (2014-2017) were compared with 169 patients who received 2214 standard IFX infusions (2005-2013). Within the rapid cohort, 55 (42.6%) were males, median age 42 years (range 18, 86), 114 (84%) had Crohn's disease (CD) with a median disease duration 5 years (0, 36). Median needle to departure time was higher in the standard than the rapid protocol group, 108 (70, 253) vs 50 (33, 90) min, P < 0.001), with a per infusion cost of $AUD 107.50 vs $49.77, respectively (both P < 0.001). There was no difference in median infusion duration or costs between rapid home vs hospital-based infusions (P = 0.21). 8 patients in the rapid infliximab cohort had an ADR compared with 23 standard infliximab recipients (RR 0.55% vs 1.04% respectively), hence a higher likelihood of ADR with standard compared to rapid infusions [RR 3.0, 95%CI (1.2, 7.7), P = 0.02]. No ADRs were observed in 405 rapid home-based infusions. A lower body mass index (< 22 kg/m2), presence of one or more extra intestinal manifestations, longer disease duration (> 3 years) and previous exposure to another biologic were each independently associated with a higher likelihood of reaction (s) to rapid infusions. All (100%) survey respondents preferred the rapid vs standard infusions, however within rapid infusion recipients, 61.3% found home based infusions more inconvenient than hospital-based infusions despite a median of 0 h per week missed from paid work and no self-reported loss of work productivity. CONCLUSION Transitioning to rapid infliximab infusions appears very safe with significant cost benefit, patient satisfaction and avails the provision of safe, efficient, home-based infliximab infusions by IBD centres worldwide.
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Affiliation(s)
- Anuj Bohra
- Department of Gastroenterology, Eastern Health, Box Hill 3128, Victoria, Australia
- Eastern Health Clinical School, Monash University, Box Hill 3128, Victoria, Australia
| | - Qurat-Al-Ain Rizvi
- Department of Gastroenterology, Eastern Health, Box Hill 3128, Victoria, Australia
| | | | - Abhinav Vasudevan
- Department of Gastroenterology, Eastern Health, Box Hill 3128, Victoria, Australia
- Eastern Health Clinical School, Monash University, Box Hill 3128, Victoria, Australia
| | - Daniel R van Langenberg
- Department of Gastroenterology, Eastern Health, Box Hill 3128, Victoria, Australia
- Eastern Health Clinical School, Monash University, Box Hill 3128, Victoria, Australia
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Yasui K, Matsuyama N, Takihara Y, Hirayama F. New insights into allergic transfusion reactions and their causal relationships, pathogenesis, and prevention. Transfusion 2020; 60:1590-1601. [DOI: 10.1111/trf.15845] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2020] [Revised: 03/22/2020] [Accepted: 04/08/2020] [Indexed: 12/13/2022]
Affiliation(s)
- Kazuta Yasui
- Japanese Red Cross Kinki Block Blood Center Ibaraki Osaka Japan
| | | | | | - Fumiya Hirayama
- Japanese Red Cross Kinki Block Blood Center Ibaraki Osaka Japan
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46
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Vigh N, Levy D. Lactic acidemia due to an infliximab infusion reaction. Am J Emerg Med 2020; 38:850.e1-850.e3. [DOI: 10.1016/j.ajem.2019.11.005] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/13/2019] [Revised: 10/02/2019] [Accepted: 11/02/2019] [Indexed: 11/16/2022] Open
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Spencer EA, Kinnucan J, Wang J, Dubinsky MC. Real-World Experience With Acute Infusion Reactions to Ustekinumab at 2 Large Tertiary Care Centers. CROHN'S & COLITIS 360 2020; 2:otaa022. [PMID: 36798650 PMCID: PMC9927818 DOI: 10.1093/crocol/otaa022] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Indexed: 01/07/2023] Open
Abstract
Background Ustekinumab is approved for Crohn's disease and Ulcerative colitis with acute infusion reactions reported at a rate of 0.9%-4.5%. Methods A retrospective chart review was conducted on inflammatory bowel disease (IBD) patients experiencing an acute infusion reaction to ustekinumab at 2 large institutions. Results Acute ustekinumab infusion reactions occurred in 16 patients with Crohn's disease (CD) and Ulcerative colitis (UC), at a rate of 0.8%-3%. Patients were all naïve to ustekinumab, receiving their initial IV induction. Ninety-three percent subsequently tolerated the injection without issues. Conclusions In this large, real-world study of acute infusion reactions to ustekinumab, the rate was similar to that seen in clinical trials-0.8%-3%.
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Affiliation(s)
- Elizabeth A Spencer
- Department of Pediatrics, Division of Pediatric Gastroenterology and Nutrition, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Jami Kinnucan
- Department of Medicine, Division of Gastroenterology, University of Michigan, Ann Arbor, Michigan, USA
| | - Julie Wang
- Department of Pediatrics, Division of Allergy and Immunology, Icahn School of Medicine at Mount Sinai, New York, New York, USA
| | - Marla C Dubinsky
- Department of Pediatrics, Division of Pediatric Gastroenterology and Nutrition, Icahn School of Medicine at Mount Sinai, New York, New York, USA
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Carballido JM, Regairaz C, Rauld C, Raad L, Picard D, Kammüller M. The Emerging Jamboree of Transformative Therapies for Autoimmune Diseases. Front Immunol 2020; 11:472. [PMID: 32296421 PMCID: PMC7137386 DOI: 10.3389/fimmu.2020.00472] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2019] [Accepted: 02/28/2020] [Indexed: 12/12/2022] Open
Abstract
Standard treatments for autoimmune and autoinflammatory disorders rely mainly on immunosuppression. These are predominantly symptomatic remedies that do not affect the root cause of the disease and are associated with multiple side effects. Immunotherapies are being developed during the last decades as more specific and safer alternatives to small molecules with broad immunosuppressive activity, but they still do not distinguish between disease-causing and protective cell targets and thus, they still have considerable risks of increasing susceptibility to infections and/or malignancy. Antigen-specific approaches inducing immune tolerance represent an emerging trend carrying the potential to be curative without inducing broad immunosuppression. These therapies are based on antigenic epitopes derived from the same proteins that are targeted by the autoreactive T and B cells, and which are administered to patients together with precise instructions to induce regulatory responses capable to restore homeostasis. They are not personalized medicines, and they do not need to be. They are precision therapies exquisitely targeting the disease-causing cells that drive pathology in defined patient populations. Immune tolerance approaches are truly transformative options for people suffering from autoimmune diseases.
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Affiliation(s)
- José M. Carballido
- Translational Medicine, Novartis Institutes for Biomedical Research, Basel, Switzerland
- Autoimmunity Transplantation and Inflammation, Novartis Institutes for Biomedical Research, Basel, Switzerland
| | - Camille Regairaz
- Autoimmunity Transplantation and Inflammation, Novartis Institutes for Biomedical Research, Basel, Switzerland
| | - Celine Rauld
- Autoimmunity Transplantation and Inflammation, Novartis Institutes for Biomedical Research, Basel, Switzerland
| | - Layla Raad
- Autoimmunity Transplantation and Inflammation, Novartis Institutes for Biomedical Research, Basel, Switzerland
| | - Damien Picard
- Translational Medicine, Novartis Institutes for Biomedical Research, Basel, Switzerland
| | - Michael Kammüller
- Translational Medicine, Novartis Institutes for Biomedical Research, Basel, Switzerland
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Behera SK, Selvarajan S, Mathews J, Shajil C, Das S, Munisamy M, Xavier AS. A Novel Desensitization Protocol for Infliximab Hypersensitivity in a 13-Year Old Patient with Pustular Psoriasis. Curr Drug Saf 2020; 14:158-162. [PMID: 30659548 DOI: 10.2174/1574886314666190119115632] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/19/2018] [Revised: 01/08/2019] [Accepted: 01/11/2019] [Indexed: 12/30/2022]
Abstract
BACKGROUND Drug hypersensitivity reactions to infliximab have been reported in pediatric patients. At times, these patients may need infliximab administration in spite of hypersensitivity. However, only a few reports of desensitization protocols are available in the literature in pediatric patients. CASE REPORT We report a case of immediate hypersensitivity reaction to intravenous infliximab in a 13-year-old child suffering from pustular psoriasis who eventually underwent a 14 step desensitization protocol for the administration of infliximab in a pediatric intensive care unit. RESULTS AND CONCLUSION Although our desensitization protocol was safe and effective, we recommend the entire desensitization procedure to be performed under the supervision of experienced personnel in a pediatric intensive care unit. Future studies with larger sample size are needed to confirm our findings.
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Affiliation(s)
- Sapan Kumar Behera
- Department of Clinical Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research, (JIPMER), Puducherry, India
| | - Sandhiya Selvarajan
- Department of Clinical Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research, (JIPMER), Puducherry, India
| | - Jerene Mathews
- Department of Dermatology & STD, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India
| | - Chandana Shajil
- Department of Dermatology & STD, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India
| | - Saibal Das
- Department of Clinical Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research, (JIPMER), Puducherry, India
| | - Malathi Munisamy
- Department of Dermatology & STD, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India
| | - Alphienes Stanley Xavier
- Department of Pharmacology, Sri Ramachandra Institute of Higher Education and Research, Chennai, India
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Kozma GT, Shimizu T, Ishida T, Szebeni J. Anti-PEG antibodies: Properties, formation, testing and role in adverse immune reactions to PEGylated nano-biopharmaceuticals. Adv Drug Deliv Rev 2020; 154-155:163-175. [PMID: 32745496 DOI: 10.1016/j.addr.2020.07.024] [Citation(s) in RCA: 354] [Impact Index Per Article: 70.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2020] [Revised: 07/28/2020] [Accepted: 07/29/2020] [Indexed: 12/20/2022]
Abstract
Conjugation of polyethylene glycols (PEGs) to proteins or drug delivery nanosystems is a widely accepted method to increase the therapeutic index of complex nano-biopharmaceuticals. Nevertheless, these drugs and agents are often immunogenic, triggering the rise of anti-drug antibodies (ADAs). Among these ADAs, anti-PEG IgG and IgM were shown to account for efficacy loss due to accelerated blood clearance of the drug (ABC phenomenon) and hypersensitivity reactions (HSRs) entailing severe allergic symptoms with occasionally fatal anaphylaxis. In addition to recapitulating the basic information on PEG and its applications, this review expands on the physicochemical factors influencing its immunogenicity, the prevalence, features, mechanism of formation and detection of anti-PEG IgG and IgM and the mechanisms by which these antibodies (Abs) induce ABC and HSRs. In particular, we highlight the in vitro, animal and human data attesting to anti-PEG Ab-induced complement (C) activation as common underlying cause of both adverse effects. A main message is that correct measurement of anti-PEG Abs and individual proneness for C activation might predict the rise of adverse immune reactions to PEGylated drugs and thereby increase their efficacy and safety.
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Affiliation(s)
- Gergely Tibor Kozma
- Nanomedicine Research and Education Center, Department of Translational Medicine, Semmelweis University Medical School, Budapest, Hungary; SeroScience Ltd, Budapest, Hungary
| | - Taro Shimizu
- Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, 1-78-1, Sho-machi, Tokushima 770-8505, Japan
| | - Tatsuhiro Ishida
- Department of Pharmacokinetics and Biopharmaceutics, Institute of Biomedical Sciences, Tokushima University, 1-78-1, Sho-machi, Tokushima 770-8505, Japan
| | - Janos Szebeni
- Nanomedicine Research and Education Center, Department of Translational Medicine, Semmelweis University Medical School, Budapest, Hungary; SeroScience Ltd, Budapest, Hungary; Department of Nanobiotechnology and Regenerative Medicine, Faculty of Health, Miskolc University, Miskolc, Hungary.
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