9/8/2014 Secukinumab in Plaque Psoriasis — Results of Two Phase 3 Trials — NEJM
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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
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ORIGINA L A RT ICLE
Secukinumab in Plaque Psoriasis — Results of Two Phase 3 Trials
Richard G. Langley, M.D., Boni E. Elew ski, M.D., Mark Lebw ohl, M.D., Kristian Reich, M.D., Ph.D., Christopher E.M.
Griffiths, M.D., Kim Papp, M.D., Ph.D., Lluís Puig, M.D., Ph.D., Hidemi Nakagaw a, M.D., Ph.D., Lynda Spelman, M.B., B.S., Bárður Sigurgeirsson, M.D., Ph.D., Enrique Rivas, M.D., Tsen-Fang Tsai, M.D., Norman Wasel, M.D., Stephen Tyring, M.D., Ph.D., Thomas Salko, B.A., Isabelle Hampele, Ph.D., Marianne Notter, M.S., Alexander Karpov, Ph.D., Silvia Helou, M.D., Ph.D., and Charis Papavassilis, M.D., Ph.D. for the ERASURE and FIXTURE Study Groups
N Engl J Med 2014; 371:326-338 July 24, 2014 DOI: 10.1056/NEJMoa1314258
MEDIA IN THIS ARTICLE FIGURE 1
Speed of Response.
FIGURE 2
Efficacy over Time.
9/8/2014 Secukinumab in Plaque Psoriasis — Results of Two Phase 3 Trials — NEJM
http://www.nejm.org/doi/full/10.1056/NEJMoa1314258?viewType=Print&viewClass=Print 2/3
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.)
Supported by Novartis Pharmaceuticals.
Disclosure forms provided by the authors are available w ith the full text of this article at NEJM.org.
Drs. Langley and Elew ski contributed equally to this article.
This article w as published on July 9, 2014, at NEJM.org.
We thank the patients w ho participated in the studies; Dr. Jörg Prinz for advice regarding the development of an earlier version of the manuscript; Dr. Izabella Messina, Mr. Vamsidhar Chaturvedula, Mr. Noel Ny Tovo, and Mr. Abhishek Dhanuka for help w ith the conduct of the ERASURE study; Ms. Katherine Kramp, Ms. Nancy Rikken, Ms. Diane Ryan, and Mr. Varun Jain (clinical managers) and Mr.
Kevin Poirier (clinical scientist), all from Novartis Pharmaceuticals, for help w ith the conduct of the FIXTURE study; Dr. Achim Güttner of Novartis Pharmaceuticals for discussions regarding the design of both studies; Dr. Oliver Sander of Novartis Pharmaceuticals for discussions regarding the design of the FIXTURE study; Ms.
Claudia Seper of Novartis Pharmaceuticals for support of study conduct; Dr. Kirtida Pandya of Novartis Pharmaceuticals for medical communications leadership; and Dr. Barry Weichman and Dr. Andrew Horgan of BioScience Communications for assistance in w riting the first draft of the manuscript.
SOURCE INFORMATION
From Dalhousie University, Halifax, NS (R.G.L.), Clinical Research (K.P.) and Probity Medical Research (K.P., L.S.), Waterloo, ON, and Stratica Medical and Probity Medical Research, Edmonton, AB (N.W.) — all in Canada; University of Alabama, Birmingham (B.E.E.); Mount Sinai Hospital, New York (M.L.); Dermatologikum Hamburg and Georg-August-Universität, Göttingen, Germany (K.R.); Dermatology Centre, Salford Royal Hospital, University of Manchester, Manchester Academic Health Science Centre, Manchester, United Kingdom (C.E.M.G.); Hospital de Sant Pau, Barcelona (L.P.); Jikei University School of Medicine, Tokyo (H.N.); Veracity Clinical Research, Woolloongabba, QLD, Australia (L.S.); Faculty of Medicine, Department of Dermatology, University of Iceland, Reykjavik (B.S.); Dermos, Guatemala City, Guatemala (E.R.); Department of Dermatology, National Taiw an University Hospital and National Taiw an University College of Medicine, Taipei (T.- F.T.); University of Texas Health Science Center and Center for Clinical Studies, Houston (S.T.); and Novartis Pharma, Basel, Sw itzerland (T.S., I.H., M.N., A.K., S.H., C.P.).
Address reprint requests to Dr. Langley at 4195 Dickson Bldg., 5820 University Ave., Dalhousie University, Halifax, NS B3H 1V7, Canada, or at
A complete list of the investigators in the Efficacy of Response and Safety of Tw o Fixed Secukinumab Regimens in Psoriasis (ERASURE) and the Full Year Investigative Examination of Secukinumab versus Etanercept Using Tw o Dosing Regimens to Determine Efficacy in Psoriasis (FIXTURE) Study Groups is provided in the Supplementary Appendix, available at NEJM.org.
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9/8/2014 Secukinumab in Plaque Psoriasis — Results of Two Phase 3 Trials — NEJM
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