Secukinumab Effective Treatment for Plaque Psoriasis

Previous  research has found that interleukin (IL)-17A stimulates keratinocytes to secrete chemokines and other proinflammatory mediators that recruit additional inflammatory cells, thus making IL-17A a master cytokine in the pathogenesis of psoriasis.

Additional research has found that IL-17A plays a crucial role in the pathogenesis of several other autoimmune diseases, such as rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, and multiple sclerosis.

Specifically, secukinumab is a recombinant, high-affinity, fully human immunoglobulin G1k monoclonal antibody that selectively binds and neutralizes IL-17A. Recent studies examined the effectiveness of secukinumab in patients with moderate-to-severe plaque psoriasis [N Engl J Med. 2014; DOI:10.1056/NEJMoa1314258]. In 2 phase 3, double-blind, 52-week trials, the researchers sought to confirm earlier findings regarding the role of IL-17A in psoriasis, assessing the safety and efficacy of secukinumab in 300 mg and 160 mg doses administered as induction therapy with an assessment at week 12 and maintenance therapy with assessment at week 52.

The ERASURE [Efficacy of Response and Safety of Two Fixed Secukinumab Regimens in Psoriasis] study compared secukinumab with placebo, while the FIXTURE [Full Year Investigative Examination of Secukinumab vs. Etanercept Using Two Dosing Regimens to Determine Efficacy in Psoriasis] study compared secukinumab with placebo and etanercept, the first tumor necrosis factor inhibitor approved for moderate-to-severe plaque psoriasis.

Patients were eligible for both studies if they were ≥18 years of age with moderate-to-severe plaque
psoriasis that had been diagnosed at least 6 months before randomization that was poorly controlled with topical treatments, phototherapy, systemic therapy, or a combination of these treatments. Patients were also required to have a Psoriasis Area and Severity Index (PASI) score of ≥12, a score of 3 or 4 on the modified Investigator’s Global Assessment, and psoriasis involvement of ≥10% of the body-surface area. Patients were excluded if they had a different form of psoriasis or psoriasis that was drug-induced. In the FIXTURE study, patients who had used etanercept previously before screening were also excluded.

The ERASURE study was conducted from June 2011 through April 2013 at 88 sites worldwide, while the FIXTURE study was conducted from June 2011 through June 2013 at 231 sites.

The ERASURE study included 738 patients and the FIXTURE study included 1306 patients. The groups were well-balanced at baseline. Patients in both studies were randomized to receive either subcutaneous secukinumab 300 mg or 150 mg doses once weekly for 5 weeks then every 4 weeks or placebo. The FIXTURE study also included a group randomized to receive etanercept 50 mg dose administered twice weekly for 12 weeks then once weekly.

The primary outcome 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% PASI score from baseline and a score of 0 (clear) or 1 (almost clear) on the 5-point modified investigator’s global assessment. Specifically in the ERASURE study, the secondary objective was to determine the superiority of secukinumab compared to placebo with regard to proportion of patients meeting the criteria for a reduction of ≥90% in the PASI score from baseline at week 12. Specifically in the FIXTURE study, the secondary objective was to determine the superiority of secukinumab compared to placebo and etanercept with regard to proportion of patients meeting the criteria for a reduction of ≥90% in the PASI score from baseline at week 12.

Efficacy was assessed throughout each study with key assessments occurring at the end of the induction period before week 12 dose was administered and again at the end of the maintenance period at week 52. Safety was evaluated by monitoring adverse events—including the severity of the event and the relationship of the event to the study drug—and by obtaining clinical laboratory measurements, assessing vital signs, and performing physical examinations at each study visit.

In both studies, secukinumab was found to be superior to both placebo and etanercept. In the
ERASURE study, the percentage of patients meeting the criteria for PASI 75 at week 12 was 81.6% for the 300 mg secukinumab group, 71.6% for the 150 mg secukinumab group, and 4.5% for the placebo group (P<.001). In the FIXTURE study, the percentage of patients meeting the criteria for PASI 75 at week 12 was 77.1% for the 300 mg secukinumab group, 67% for the 150 mg secukinumab group, 44% for the etanercept group, and 4.9% for the placebo group (P<.001).

In the ERASURE study, the proportion of patients with a response of 0 or 1 in the modified investigator’s global assessment at week 12 was 65.3% for the 300 mg secukinumab group, 51.2% for the 150 mg secukinumab group, and 2.4% for the placebo group (P<.001). In the FIXTURE study, the proportion of patients with a response of 0 or 1 in the modified investigator’s global assessment at week 12 was 62.5% for the 300 mg secukinumab group, 51.1% for the 150 mg secukinumab group, 27.2% for the etanercept group, and 2.8% for the placebo group (P<.001).

Infections associated with secukinumab use were higher than placebo but similar to etanercept.
The researchers noted some limitations of the study, including that few patients continued to receive placebo after week 12, which limited the comparisons with this group during the maintenance period.
The researchers concluded that secukinumab was effective for moderate-to-severe plaque psoriasis, thus validating IL-17A as a therapeutic target.—Kerri Fitzgerald