Journal ArticleDOI
Immunogenicity of anti-TNF biologic therapies for rheumatoid arthritis.
TLDR
Investigations to determine the optimal treatment regimen required to minimize the likelihood of ADA formation might be an effective and practical way to deal with the immunogenicity of anti-TNF biologic agents for RA.Abstract:
Currently, five anti-TNF biologic agents are approved for the treatment of rheumatoid arthritis (RA): adalimumab, infliximab, etanercept, golimumab and certolizumab pegol. Formation of anti-drug antibodies (ADA) has been associated with all five agents. In the case of adalimumab and infliximab, immunogenicity is strongly linked to subtherapeutic serum drug levels and a lack of clinical response, but for the other three agents, data on immunogenicity are scarce, suggesting that further research would be valuable. Low ADA levels might not influence the efficacy of anti-TNF therapy, whereas high ADA levels impair treatment efficacy by considerably reducing unbound drug levels. Immunogenicity is not only an issue in patients treated with anti-TNF biologic agents; the immunogenicity of other therapeutic proteins, such as factor VIII and interferons, is well known and has been investigated for many years. The results of such studies suggest that investigations to determine the optimal treatment regimen (drug dosing, treatment schedule and co-medication) required to minimize the likelihood of ADA formation might be an effective and practical way to deal with the immunogenicity of anti-TNF biologic agents for RA.read more
Citations
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Journal ArticleDOI
Regulation of tumour necrosis factor signalling: live or let die
TL;DR: The role of TNF in inflammatory and autoimmune diseases is discussed, up-to-date and future treatment strategies for these disorders are discussed, and how TNF-induced survival signals are distinguished from those that lead to cell death.
Journal ArticleDOI
TNF and TNF-receptors: From mediators of cell death and inflammation to therapeutic giants – past, present and future
TL;DR: The therapeutic modulation of TNF now moves into the era of personalized medicine with society's challenging expectations of durable treatment success and of achieving long-term disease remission.
Journal ArticleDOI
Update on the Pathomechanism, Diagnosis, and Treatment Options for Rheumatoid Arthritis.
TL;DR: This review summarizes the current understanding of the underlying pathomechanism, diagnosis of RA, as well as the mode of action, clinical benefits, and side-effects of the currently available DMARDs.
Journal ArticleDOI
Tocilizumab: A Review in Rheumatoid Arthritis.
TL;DR: Given its low risk of immunogenicity, the flexibility of IV and SC administration and the convenience of the once-weekly, self-administered, SC regimen, tocilizumab provides an effective treatment for severe, active and progressive RA in adults not previously treated with methotrexate and an effective biologic first- or subsequent-line treatment in adults who have either responded inadequately to or were intolerant of previous therapy with ≥ 1 csDMARD or TNF inhibitor.
Journal ArticleDOI
Tumor Necrosis Factor Inhibitors for Inflammatory Bowel Disease
TL;DR: A 35-year-old man presents with an exacerbation of Crohn’s ileocolitis, and the gastroenterologist recommends treatment with a tumor necrosis factor (TNF) inhibitor.
References
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Journal ArticleDOI
A trial of etanercept, a recombinant tumor necrosis factor receptor:Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate.
Michael E. Weinblatt,Joel M. Kremer,Arthur D. Bankhurst,Ken J. Bulpitt,Roy Fleischmann,Robert I. Fox,Christopher G. Jackson,Mary Lange,Daniel Burge +8 more
TL;DR: In patients with persistently active rheumatoid arthritis, the combination of etanercept and methotrexate was safe and well tolerated and provided significantly greater clinical benefit than metotrexate alone.
Journal ArticleDOI
Influence of immunogenicity on the long-term efficacy of infliximab in Crohn's disease.
Filip Baert,Maja Noman,Severine Vermeire,Gert Van Assche,Geert D' Haens,An Carbonez,Paul Rutgeerts +6 more
TL;DR: The development of antibodies against infliximab is associated with an increased risk of infusion reactions and a reduced duration of response to treatment, and concomitant immunosuppressive therapy reduces the magnitude of the immunogenic response.
Journal ArticleDOI
Adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial.
Michael E. Weinblatt,Edward C. Keystone,Daniel E. Furst,Larry W. Moreland,Michael H. Weisman,C. Birbara,Leah A. Teoh,Steven A. Fischkoff,Elliot Chartash +8 more
TL;DR: The addition of adalimumab at a dosage of 20 mg, 40 mg, or 80 mg administered subcutaneously every other week to long-term MTX therapy in patients with active RA provided significant, rapid, and sustained improvement in disease activity over 24 weeks compared with MTX plus placebo.
Journal ArticleDOI
Randomised double-blind comparison of chimeric monoclonal antibody to tumour necrosis factor alpha (cA2) versus placebo in rheumatoid arthritis.
M J Elliott,Ravinder Nath Maini,Marc Feldmann,Joachim R. Kalden,C Antoni,Josef S. Smolen,B Leeb,F. C. Breedveld,J D Macfarlane,H Bijl +9 more
TL;DR: The results provide the first good evidence that specific cytokine blockade can be effective in human inflammatory disease and define a new direction for the treatment of rheumatoid arthritis.
Journal ArticleDOI
Therapeutic efficacy of multiple intravenous infusions of anti-tumor necrosis factor alpha monoclonal antibody combined with low-dose weekly methotrexate in rheumatoid arthritis.
Ravinder N. Maini,Ferdinand C. Breedveld,Joachim R. Kalden,Josef S Smolen,Diana Davis,John D. Macfarlane,C Antoni,Burkhard F. Leeb,M J Elliott,James N. Woody,Thomas F. Schaible,Marc Feldmann +11 more
TL;DR: Multiple infusions of cA2 were effective and well tolerated, with the best results occurring at 3 and 10 mg/kg either alone or in combination with MTX in approximately 60% of patients with active RA despite therapy with low-dose MTX.