Secukinumab in plaque psoriasis - Results of two phase 3 trials
Journal
New England Journal of Medicine
Journal Volume
371
Journal Issue
4
Pages
326-338
Date Issued
2014
Author(s)
Langley R.G.
Elewski B.E.
Lebwohl M.
Reich K.
Griffiths C.E.M.
Papp K.
Puig L.
Nakagawa H.
Spelman L.
Sigurgeirsson B.
Rivas E.
Wasel N.
Tyring S.
Salko T.
Hampele I.
Notter M.
Karpov A.
Helou S.
Papavassilis C.
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. Copyright ? 2014 Massachusetts Medical Society.
SDGs
Other Subjects
etanercept; placebo; secukinumab; adult; article; clinical effectiveness; comparative effectiveness; controlled study; disease severity; double blind procedure; drug dose comparison; drug dose regimen; drug efficacy; drug response; drug safety; female; food and drug administration; human; maintenance therapy; major clinical study; male; multicenter study; outcome assessment; phase 3 clinical trial; priority journal; Psoriasis Area and Severity Index; psoriasis vulgaris; randomized controlled trial; Adult; Antibodies; Antibodies, Monoclonal; Double-Blind Method; Female; Humans; Immunoglobulin A; Immunoglobulin G; Immunosuppressive Agents; Infection; Injections, Subcutaneous; Interleukin-17; Male; Middle Aged; Psoriasis; Receptors, Tumor Necrosis Factor
Publisher
Massachussetts Medical Society
Type
journal article