At least two-thirds of adults with plaque psoriasis treated with the fully human anti-interleukin-17A monoclonal antibody secukinumab achieved PASI 75 at 12 weeks in two related randomized phase III trials. The findings were reported online July 9 in the New England Journal of Medicine.
In the ERASURE (Efficacy of Response and Safety of Two Fixed Secukinumab Regimens in Psoriasis) trial, a multicenter, double-blind study involving 738 patients, the proportions of patients who achieved a 75% or greater reduction in Psoriasis Area and Severity Index (PASI 75) score at 12 weeks were 81.6%, 71.6%, and 4.5% with 300 mg of secukinumab, 150 mg of secukinumab, and placebo, respectively.
Dr. Richard Langley
In the FIXTURE (Full Year Investigative Examination of Secukinumab vs. Etanercept Using Two Dosing Regimens) study, a multicenter, double-blind, active-controlled study involving 1,306 patients, the proportions meeting PASI 75 were 77.1% and 67% for 300 and 150 mg, respectively, compared with 44% for etanercept and 4.9% for placebo.
The difference between each secukinumab dose and its comparators was statistically significant in both studies, Dr. Richard G. Langley of Dalhousie University, Halifax, N.S., Dr. Boni Elewski of the University of Alabama, Birmingham, and their colleagues reported on behalf of the ERASURE and FIXTURE Study Groups.
The investigators also found that the proportions of patients with a response of 0 or 1 on the modified investigator’s global assessment at 12 weeks were 65.3%, 51.2%, and 2.4% for the 300- and 150-mg secukinumab doses and placebo, respectively, in ERASURE; and 62.5% and 51.1% for the 300- and 150-mg doses, 27.2% for etanercept, and 2.8% for placebo in FIXTURE (N. Engl. J. Med. 2014 July 9 [doi: 10.1056/NE/NEJMoa314258]).
The differences between each secukinumab dose and its comparators were significant for this measure as well, the investigators reported.
Secukinumab at the 300- and 150-mg doses in both ERASURE and FIXTURE was also superior to placebo (and in FIXTURE, superior to etanercept) for all secondary efficacy endpoints, including PASI 90 and PASI 100 response at week 12; patient reports of itching, pain, and scaling on the Psoriasis Symptom Diary at week 12; and Dermatology Life Quality Index scores.
Both ERASURE and FIXTURE were designed to evaluate the safety of secukinumab as induction therapy with assessment at week 12, and as maintenance therapy with assessment at week 52. Subjects were aged 18 years or older with poorly controlled, moderate to severe plaque psoriasis that had been diagnosed at least 6 months prior, and with a PASI score of 12 or higher, a modified investigator’s global assessment score of 3 or 4, and involvement of 10% or more of their body surface area.
ERASURE was conducted from June 2011 to April 2013 at 88 sites worldwide, and FIXTURE was conducted from June 2011 to June 2013 at 231 sites. Patients in the 300-mg groups received two 150-mg subcutaneous injections of secukinumab, and those in the 150-mg group received one 150-mg injection of secukinumab, and one placebo injection. Etanercept was given at a dose of 50 mg administered subcutaneously twice weekly from baseline until week 12, and then once weekly through week 51.
Adverse events were more common in patients treated with secukinumab in ERASURE; 55% of patients in the 300-mg group, 60.4% in the 150-mg group, and 47% in the placebo group experienced at least one adverse event during the induction period, and 29.4%, 26.9%, and 16.2% in those groups, respectively, experienced infections and/or infestations. The most common adverse events were nasopharyngitis, headache, and upper respiratory tract infection.
The incidence of adverse events in FIXTURE was similar in those receiving secukinumab and etanercept, and was greater in both groups than in the placebo group. Infections and infestations occurred in 26.7%, 30.9%, 24.5%, and 19.3% of those receiving 300 mg of secukinumab, 150 mg of secukinumab, etanercept, and placebo, respectively. However, candida infections were more common with secukinumab than with etanercept (4.7%, 2.3%, and 1.2% of patients in the 300- and 150-mg secukinumab groups and the etanercept group, respectively, had candida infections). All candida infections in the secukinumab group were mild or moderate, and two of four infections in the etanercept group were severe.
Grade 3 neutropenia occurred in nine patients receiving secukinumab and in no patients receiving etanercept.
"The results of these phase 3 studies validate interleukin-17A as an important therapeutic target in moderate to severe plaque psoriasis, confirming earlier findings from basic research and phase 2 trials of secukinumab that suggested that interleukin-17A plays a role in the pathogenesis of psoriasis," the investigators said.
Interleukin-17A plays a key role in host defense, specifically in mucocutaneous microbial surveillance, they added.