Secukinumab in Plaque Psoriasis - Results of Two Phase 3 Trials
Por:
Langley, RG, Elewski, BE, Lebwohl, M, Reich, K, Griffiths, CEM, Papp, K, Puig, L, Nakagawa, H, Spelman, L, Sigurgeirsson, B, Rivas, E, Tsai, TF, Wasel, N, Tyring, S, Salko, T, Hampele, I, Notter, M, Karpov, A, Helou, S, Papavassilis, C
Publicada:
24 jul 2014
Resumen:
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.
Filiaciones:
Langley, RG:
Dalhousie Univ, Halifax, NS B3H 1V7, Canada
Elewski, BE:
Univ Alabama Birmingham, Birmingham, AL USA
Lebwohl, M:
Mt Sinai Hosp, New York, NY 10029 USA
Reich, K:
Dermatologikum Hamburg, Hamburg, Germany
Univ Gottingen, D-37073 Gottingen, Germany
Griffiths, CEM:
Univ Manchester, Manchester Acad Hlth Sci Ctr, Salford Royal Hosp, Dermatol Ctr, Manchester, Lancs, England
Papp, K:
Clin Res, Waterloo, ON, Canada
Prob Med Res, Waterloo, ON, Canada
Puig, L:
Hosp Santa Creu & Sant Pau, Barcelona, Spain
Nakagawa, H:
Jikei Univ, Sch Med, Tokyo, Japan
Spelman, L:
Prob Med Res, Waterloo, ON, Canada
Verac Clin Res, Woolloongabba, Qld, Australia
Sigurgeirsson, B:
Univ Iceland, Dept Dermatol, Fac Med, Reykjavik, Iceland
Rivas, E:
Dermos, Guatemala City, Guatemala
Tsai, TF:
Natl Taiwan Univ Hosp, Dept Dermatol, Taipei, Taiwan
Natl Taiwan Univ, Coll Med, Taipei 10764, Taiwan
Wasel, N:
Strat Med & Prob Med Res, Edmonton, AB, Canada
Tyring, S:
Univ Texas Hlth Sci Ctr Houston, Houston, TX 77030 USA
Ctr Clin Studies, Houston, TX USA
Salko, T:
Novartis Pharmaceut, Basel, Switzerland
Hampele, I:
Novartis Pharmaceut, Basel, Switzerland
Notter, M:
Novartis Pharmaceut, Basel, Switzerland
Karpov, A:
Novartis Pharmaceut, Basel, Switzerland
Helou, S:
Novartis Pharmaceut, Basel, Switzerland
Papavassilis, C:
Novartis Pharmaceut, Basel, Switzerland
Green Published
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