Secukinumab in plaque psoriasis--results of two phase 3 trials.
Richard G. Langley,Boni E. Elewski,Mark Lebwohl,Kristian Reich,Christopher E.M. Griffiths,Kim A. Papp,Lluís Puig,Hidemi Nakagawa,Lynda Spelman,Bárður Sigurgeirsson,Enrique Rivas,Tsen-Fang Tsai,Norman Wasel,Stephen K. Tyring,Thomas Salko,Isabelle Hampele,Marianne Notter,Alexander Karpov,Silvia Helou,Charis Papavassilis +19 more
TLDR
Secukinumab was effective for psoriasis in two randomized trials, validating interleukin-17A as a therapeutic target and the rates of infection were higher with secuk inumab than with placebo in both studies and were similar to those with etanercept.Abstract:
BACKGROUND: Interleukin-17A is considered to be central to the pathogenesis of psoriasis. We evaluated secukinumab, a fully human anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe plaque psoriasis. METHODS: In two phase 3, double-blind, 52-week trials, ERASURE (Efficacy of Response and Safety of Two Fixed Secukinumab Regimens in Psoriasis) and FIXTURE (Full Year Investigative Examination of Secukinumab vs. Etanercept Using Two Dosing Regimens to Determine Efficacy in Psoriasis), we randomly assigned 738 patients (in the ERASURE study) and 1306 patients (in the FIXTURE study) to subcutaneous secukinumab at a dose of 300 mg or 150 mg (administered once weekly for 5 weeks, then every 4 weeks), placebo, or (in the FIXTURE study only) etanercept at a dose of 50 mg (administered twice weekly for 12 weeks, then once weekly). The objective of each study was to show the superiority of secukinumab over placebo at week 12 with respect to the proportion of patients who had a reduction of 75% or more from baseline in the psoriasis area-and-severity index score (PASI 75) and a score of 0 (clear) or 1 (almost clear) on a 5-point modified investigator's global assessment (coprimary end points). RESULTS: The proportion of patients who met the criterion for PASI 75 at week 12 was higher with each secukinumab dose than with placebo or etanercept: in the ERASURE study, the rates were 81.6% with 300 mg of secukinumab, 71.6% with 150 mg of secukinumab, and 4.5% with placebo; in the FIXTURE study, the rates were 77.1% with 300 mg of secukinumab, 67.0% with 150 mg of secukinumab, 44.0% with etanercept, and 4.9% with placebo (P<0.001 for each secukinumab dose vs. comparators). The proportion of patients with a response of 0 or 1 on the modified investigator's global assessment at week 12 was higher with each secukinumab dose than with placebo or etanercept: in the ERASURE study, the rates were 65.3% with 300 mg of secukinumab, 51.2% with 150 mg of secukinumab, and 2.4% with placebo; in the FIXTURE study, the rates were 62.5% with 300 mg of secukinumab, 51.1% with 150 mg of secukinumab, 27.2% with etanercept, and 2.8% with placebo (P<0.001 for each secukinumab dose vs. comparators). The rates of infection were higher with secukinumab than with placebo in both studies and were similar to those with etanercept. CONCLUSIONS: Secukinumab was effective for psoriasis in two randomized trials, validating interleukin-17A as a therapeutic target. (Funded by Novartis Pharmaceuticals; ERASURE and FIXTURE ClinicalTrials.gov numbers, NCT01365455 and NCT01358578, respectively.).read more
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Immune-Related Adverse Events Associated with Immune Checkpoint Blockade
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2016 update of the ASAS-EULAR management recommendations for axial spondyloarthritis
Désirée van der Heijde,Sofia Ramiro,Robert Landewé,Xenofon Baraliakos,Filip Van den Bosch,Alexandre Sepriano,Alexandre Sepriano,Andrea Regel,Adrian Ciurea,Hanne Dagfinrud,Maxime Dougados,Maxime Dougados,Floris A. van Gaalen,Pál Géher,Irene E. van der Horst-Bruinsma,Robert D. Inman,Merryn Jongkees,Uta Kiltz,Tore K Kvien,Pedro Machado,Helena Marzo-Ortega,Anna Molto,Anna Molto,Victoria Navarro-Compán,Salih Ozgocmen,Fernando Pimentel-Santos,John D. Reveille,Martin Rudwaleit,Martin Rudwaleit,J. Sieper,Percival D. Sampaio-Barros,Dieter Wiek,Jürgen Braun +32 more
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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.
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Psoriasis Pathogenesis and Treatment.
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Comparison of ixekizumab with etanercept or placebo in moderate-to-severe psoriasis (UNCOVER-2 and UNCOVER-3): results from two phase 3 randomised trials
Christopher E.M. Griffiths,Kristian Reich,Mark Lebwohl,Peter C.M. van de Kerkhof,Carle Paul,Alan Menter,Gregory S Cameron,J. Erickson,L. Zhang,Roberta J. Secrest,Susan Ball,Daniel K. Braun,Olawale Osuntokun,Michael P. Heffernan,Brian J. Nickoloff,Kim A. Papp +15 more
TL;DR: Two studies of ixekizumab compared with placebo or etanercept to assess the safety and efficacy of specifically targeting interleukin 17A in patients with widespread moderate-to-severe psoriasis met the primary endpoints.
References
More filters
Journal ArticleDOI
Interleukin 17–producing CD4 + effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages
Laurie E. Harrington,Robin D. Hatton,Paul R. Mangan,Henrietta Turner,Theresa L. Murphy,Kenneth M. Murphy,Casey T. Weaver +6 more
TL;DR: Findings provide a basis for understanding how inhibition of IFN-γ signaling enhances development of pathogenic TH-17 effector cells that can exacerbate autoimmunity.
Journal ArticleDOI
A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17
Heon Park,Zhaoxia Li,Xuexian O. Yang,Seon Hee Chang,Roza Nurieva,Yi Hong Wang,Ying Wang,Leroy Hood,Zhou Zhu,Qiang Tian,Chen Dong +10 more
TL;DR: In vivo, antibody to IL- 17 inhibited chemokine expression in the brain during experimental autoimmune encephalomyelitis, whereas overexpression of IL-17 in lung epithelium caused Chemokine production and leukocyte infiltration, indicating a unique T helper lineage that regulates tissue inflammation.
Journal ArticleDOI
Dermatology Life Quality Index (DLQI)—a simple practical measure for routine clinical use
Andrew Yule Finlay,G. K. Khan +1 more
TL;DR: This study confirmed that a topic eczema, psoriasis and generalized pruritus have a greater impact on quality of life than acne, basal cell carcinomas and viral warts.
Journal ArticleDOI
Pathogenesis and clinical features of psoriasis.
TL;DR: Comorbidities of psoriasis are attracting interest, and include impairment of quality of life and associated depressive illness, cardiovascular disease, and a seronegative arthritis known as psoriatic arthritis.
Journal ArticleDOI
Chronic Mucocutaneous Candidiasis in Humans with Inborn Errors of Interleukin-17 Immunity
Anne Puel,Sophie Cypowyj,Jacinta Bustamante,Jill F. Wright,Luyan Liu,Hye Kyung Lim,Mélanie Migaud,Laura Israel,Maya Chrabieh,Magali Audry,Matthew Gumbleton,Antoine Toulon,Christine Bodemer,Jamila El-Baghdadi,Matthew J. Whitters,Theresa Paradis,Jonathan Brooks,Mary Collins,Neil M. Wolfman,Saleh Al-Muhsen,Miguel Galicchio,Laurent Abel,Laurent Abel,Capucine Picard,Jean-Laurent Casanova +24 more
TL;DR: These experiments of nature indicate that human IL-17A andIL-17F are essential for mucocutaneous immunity against C. albicans, but otherwise largely redundant.