First IL-17A inhibitor
Secukinumab is a monoclonal antibody that selectively binds to and neutralises interleukin-17A (IL-17A), a protein involved in the development of psoriasis and found in significantly higher concentrations in psoriasis-affected skin. This inhibits the release of proinflammatory cytokines, chemokines and mediators of tissue damage and reduces IL-17A-mediated contributions to autoimmune and inflammatory diseases.
The safety and efficacy of secukinumab in patients with moderate to severe plaque psoriasis were assessed in four randomised, double-blind, phase III trials. Participants were candidates for phototherapy or systemic therapy.
In the 52-week ERASURE (n=738) and FIXTURE (n=1306) studies, patients received subcutaneous secukinumab 300mg or 150mg (administered once weekly for 5 weeks, then every 4 weeks), etanercept 50mg (FIXTURE study only; administered twice weekly until week 12 then once weekly) or placebo.
At week 12, the proportion of patients who achieved a ≥75% improvement in Psoriasis Area and Severity Index (PASI 75) was significantly higher with secukinumab than with placebo or etanercept (ERASURE, 81.6% with secukinumab 300mg vs 4.5% with placebo; FIXTURE, 77.1% with secukinumab 300mg vs 44.0% with etanercept and 4.9% with placebo; p<0.001 for all).
The proportion of patients with a response of 0 or 1 on the modified investigator's global assessment at week 12 was also higher with secukinumab than with placebo or etanercept (ERASURE, 65.3% with secukinumab 300mg vs 2.4% with placebo; FIXTURE, 62.5% with secukinumab 300mg vs 27.2% with etanercept and 2.8% with placebo; p<0.001 for all).
Continued treatment past week 12 was associated with sustained high response rates in most patients at week 52.
The FEATURE (n=177) and JUNCTURE (n=182) studies evaluated the safety, tolerability and usability of secukinumab self-administration. Participants were randomised to receive secukinumab 150mg or 300mg or placebo.
In both trials significantly more patients receiving secukinumab at either dose achieved PASI 75 at week 12 than did those receiving placebo (p<0.0001). Patient-reported acceptability of self-administration was high throughout both studies.
The most commonly reported adverse effects of secukinumab were upper respiratory tract infections including nasopharyngitis and rhinitis.