Secukinumab 2-weekly vs. 4-weekly dosing in patients with plaque-type psoriasis: results from the randomized GAIN study.

Abstract

Secukinumab is a fully human monoclonal antibody that selectively neutralizes interleukin-17A and shows long-lasting efficacy and safety in plaque psoriasis. More evidence is required to optimize secukinumab dosing according to clinical response. GAIN compared the efficacy and safety of secukinumab 300mg every 2weeks (q2w) with 300mg every 4weeks (q4w) in patients achieving≥75% improvement in Psoriasis Area and Severity Index (PASI 75) but not PASI 90 after 16weeks. In total, 772 patients with moderate-to-severe plaque psoriasis received secukinumab 300mg subcutaneously at baseline and weeks 1, 2, 3 and 4, then q4w until week 16. At week 16, patients with PASI≥75 to PASI<90 were randomized 1:1 to continue q4w dosing (n=162) or switch to q2w (n=163) to week 32. The primary endpoint was superiority of q2w to q4w dosing for PASI 90 response at week 32. PASI 90 response at week 32 was numerically greater with secukinumab 300mg q2w than with secukinumab 300mg q4w in suboptimal responders, but this did not reach statistical significance (64·4% vs. 57·4%; odds ratio 0·64, 95% confidence interval 0·39-1·07; P=0·087). Although the primary endpoint was not met, absolute PASI was significantly lower at week 32 in q2w vs. q4w patients (2·11 vs. 2·84, P=0·024). Significantly more patients with q2w vs. q4w dosing showed minimal disease activity (Investigator's Global Assessment score 0 or 1: 73·0% vs. 64·1%, P<0·05) and improved quality of life (Dermatology Life Quality Index score 0 or 1: 58·9% vs. 50·6%, P<0·05) at week 32. No new or unexpected safety signals arose. Most patients achieved PASI 90 response with secukinumab q4w. There was potential benefit of q2w dosing in some suboptimal responders. Continued q4w treatment can improve response even after 16weeks.