Journal ArticleDOI
Efficacy and safety of secukinumab in patients with rheumatoid arthritis: a phase II, dose-finding, double-blind, randomised, placebo controlled study
Mark C. Genovese,Patrick Durez,Hanno B. Richards,Jerzy Supronik,Eva Dokoupilova,Mazurov Vi,Jacob A. Aelion,Sang-Heon Lee,Christine E Codding,Herbert Kellner,Takashi Ikawa,Sophie Hugot,Shephard Mpofu +12 more
TLDR
The safety profile of secukinumab was consistent with that seen with other biological agents, and most adverse events (AE) were mild to moderate in severity, and there were no unexpected safety signals and no specific organ-related toxicities.Abstract:
OBJECTIVE: To assess the safety and efficacy of secukinumab, a fully human monoclonal anti-interleukin-17A antibody, in patients with rheumatoid arthritis (RA). METHODS: Patients (n=237) with inadequate response to methotrexate were randomly assigned to receive monthly subcutaneous injections of secukinumab 25 mg, 75 mg, 150 mg, 300 mg or placebo. The primary endpoint was the American College of Rheumatology 20% response (ACR20) at week 16. RESULTS: Demographics and baseline characteristics were comparable across all treatment groups. The primary efficacy endpoint was not achieved: the proportion of ACR20 responders at week 16 with secukinumab 25-300 mg was 36.0-53.7% versus placebo (34%). Disease activity score in 28 joints (DAS28)-C-reactive protein (CRP) was a secondary endpoint and clinically relevant decreases with secukinumab 75-300 mg were reported versus placebo. Serum high sensitivity CRP levels at week 16 were significantly reduced with secukinumab 75 mg, 150 mg and 300 mg doses versus placebo. The safety profile of secukinumab was consistent with that seen with other biological agents. Most adverse events (AE) were mild to moderate in severity. Infections were slightly more frequent with secukinumab than placebo. Six serious AE were reported: secukinumab 75 mg (one), secukinumab 300 mg (four) and placebo (one). CONCLUSIONS: ACR20 response rates differed between secukinumab 75 mg, 150 mg and 300 mg doses and placebo; however, the primary efficacy endpoint was not achieved. Greater decreases in DAS28 were observed with secukinumab 75 mg, 150 mg and 300 mg than placebo. There were no unexpected safety signals and no specific organ-related toxicities. Further trials with secukinumab in the treatment of RA are warranted.read more
Citations
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Journal ArticleDOI
Diagnosis and Management of Rheumatoid Arthritis: A Review.
Daniel Aletaha,Josef S Smolen +1 more
TL;DR: A treat-to-target strategy aimed at reducing disease activity by at least 50% within 3 months and achieving remission or low disease activity within 6 months, with sequential drug treatment if needed, can prevent RA-related disability.
Journal ArticleDOI
Secukinumab, an Interleukin-17A Inhibitor, in Ankylosing Spondylitis
Dominique Baeten,Joachim Sieper,Jürgen Braun,Xenofon Baraliakos,Maxime Dougados,Paul Emery,Atul Deodhar,Brian Porter,Ruvie Martin,Mats Andersson,Shephard Mpofu,Hanno B. Richards +11 more
TL;DR: Secukinumab at a subcutaneous dose of 150 mg, with either sub cutaneous or intravenous loading, provided significant reductions in the signs and symptoms of ankylosing spondylitis at week 16, and was sustained through 52 weeks.
Journal ArticleDOI
Anti-interleukin-17A monoclonal antibody secukinumab in treatment of ankylosing spondylitis: a randomised, double-blind, placebo-controlled trial
Dominique Baeten,Xenofon Baraliakos,Jürgen Braun,Joachim Sieper,Paul Emery,Désirée van der Heijde,Iain B. McInnes,Jacob M van Laar,Robert Landewé,Paul Wordsworth,Paul Wordsworth,Jürgen Wollenhaupt,Herbert Kellner,Jacqueline E Paramarta,Jiawei Wei,Arndt Brachat,Stephan Bek,Didier Laurent,Yali Li,Ying A Wang,Arthur P. Bertolino,Sandro Gsteiger,Andrew M Wright,Wolfgang Hueber +23 more
TL;DR: Secukinumab rapidly reduced clinical or biological signs of active ankylosing spondylitis and was well tolerated, making it the first targeted therapy that is an alternative to tumour necrosis factor inhibition to reach its primary endpoint in a phase 2 trial.
Journal ArticleDOI
Th17 Cell Pathway in Human Immunity: Lessons from Genetics and Therapeutic Interventions
TL;DR: It is discussed that although there are similarities when Th17 cell pathway molecules are modulated, each molecule has unique non-Th17 cell features that lead to different functional outcomes.
Journal ArticleDOI
Rheumatoid arthritis therapy reappraisal: strategies, opportunities and challenges
Josef S Smolen,Daniel Aletaha +1 more
TL;DR: The data available suggest that, in most patients with established disease, cessation of biologic therapy will be followed by disease flares, whereas a reduction of dose or an increase in the interval between doses enables maintenance of treatment success, which underscores the importance of research into the cause of RA so that curative therapies can be developed.
References
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Journal ArticleDOI
The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis.
Frank C. Arnett,Steven M. Edworthy,Daniel A. Bloch,Dennis J. McShane,James F. Fries,Norman S. Cooper,L. A. Healey,Stephen R. Kaplan,Matthew H. Liang,Harvinder S. Luthra,Thomas A. Medsger,Donald M. Mitchell,David H. Neustadt,Robert S. Pinals,Jane G. Schaller,John T. Sharp,Ronald L. Wilder,Gene G. Hunder +17 more
TL;DR: The revised criteria for the classification of rheumatoid arthritis (RA) were formulated from a computerized analysis of 262 contemporary, consecutively studied patients with RA and 262 control subjects with rheumatic diseases other than RA (non-RA).
Journal ArticleDOI
Anti-TNF Antibody Therapy in Rheumatoid Arthritis and the Risk of Serious Infections and Malignancies: Systematic Review and Meta-analysis of Rare Harmful Effects in Randomized Controlled Trials
Tim Bongartz,Alex J. Sutton,Michael J. Sweeting,Iain Buchan,Eric L. Matteson,Victor M. Montori +5 more
TL;DR: There is evidence of an increased risk of serious infections and a dose-dependent increasedrisk of malignancies in patients with rheumatoid arthritis treated with anti-TNF antibody therapy.
Journal ArticleDOI
IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis
Shigeru Kotake,Nobuyuki Udagawa,Naoyuki Takahashi,Kenichiro Matsuzaki,Kanami Itoh,Shigeru Ishiyama,Seiji Saito,Kazuhiko Inoue,Naoyuki Kamatani,Matthew T. Gillespie,T. John Martin,Tatsuo Suda +11 more
TL;DR: It is suggested that IL-17 first acts on osteoblasts, which stimulates both COX-2-dependent PGE2 synthesis and ODF gene expression, which in turn induce differentiation of osteoclast progenitors into mature osteoclasts, and that IL -17 is a crucial cytokine for osteoclastic bone resorption in RA patients.
Journal ArticleDOI
T cell interleukin-17 induces stromal cells to produce proinflammatory and hematopoietic cytokines.
François Fossiez,Odile Djossou,Pascale Chomarat,Leopoldo Flores-Romo,Smina Ait-Yahia,C Maat,Jean-Jacques Pin,Pierre Garrone,Eric Garcia,Sem Saeland,D Blanchard,Claude Gaillard,B Das Mahapatra,E Rouvier,Pierre Golstein,Jacques Banchereau,Serge Lebecque +16 more
TL;DR: Observations suggest that hIL-17 may constitute an early initiator of the T cell-dependent inflammmatory reaction; and an element of the cytokine network that bridges the immune system to hematopoiesis.
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Interleukin-17 and type 17 helper T cells.
TL;DR: Type 17 helper T cells (Th17) — a third class of T cells — and their major cytokine, interleukin-17, are essential for the defense against certain fungi, extracellular bacteria, and Mycob bacteria.
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