Secukinumab dosing every 2 weeks demonstrated superior efficacy compared with dosing every 4 weeks in patients with psoriasis weighing 90 kg or more: results of a randomized controlled trial

Abstract

Background: Obesity is a common comorbidity of psoriasis and can attenuate response to biologic treatment.

Objectives: To investigate the efficacy, safety and tolerability of secukinumab 300 mg every 2 weeks (Q2W) vs. secukinumab 300 mg every 4 weeks (Q4W) in patients with a higher bodyweight.

Methods: In this multicentre, double-blind, parallel-group trial, 331 patients with moderate-to-severe chronic plaque psoriasis weighing ≥ 90 kg were randomized to receive secukinumab 300 mg Q2W or secukinumab 300 mg Q4W. Patients who did not achieve Psoriasis Area and Severity Index (PASI) 90 at week 16 on the Q4W regimen were reallocated to remain on the Q4W regimen or uptitrate to Q2W.

Results: At week 16, Q2W dosing (n = 165) led to significantly higher PASI 90 responses vs. Q4W [n = 166; 73.2% vs. 55.5%, one-sided P-value = 0.0003, odds ratio estimate (95% confidence intervals): 2.3 (1.4-3.8)]. At week 52, higher efficacy responses were maintained in the Q2W arm (n = 165) vs. Q4W (n = 83); PASI 75: 88.9% vs. 74.8%; PASI 90: 76.4% vs. 52.4%; PASI 100: 46.7% vs. 27.3%; Investigator's Global Assessment 0/1: 75.9% vs. 55.6% and Dermatology Life Quality Index 0/1: 66.1% vs. 48.8%. PASI 90 nonresponders at week 16 who uptitrated to Q2W (n = 31) showed higher efficacy responses at week 32 (16 weeks post-uptitration, PASI 90: 38.7% vs. 16.5%) vs. those who remained on Q4W (n = 40). Safety results were comparable across treatment arms and consistent with the established secukinumab safety profile.

Conclusions: Secukinumab 300 mg Q2W demonstrated superior and sustained efficacy compared with Q4W in patients with moderate-to-severe plaque psoriasis weighing ≥ 90 kg. PASI 90 nonresponders derived additional benefits from uptitration to a Q2W regimen (ClinicalTrials.gov identifier: NCT03504852). What is already known about this topic? Obesity is a common comorbidity of psoriasis and can attenuate response to biologic treatment. Secukinumab is a fully human monoclonal antibody that selectively neutralizes interleukin-17A in the treatment of moderate-to-severe plaque psoriasis. Subgroup analyses of previous study results and pharmacokinetic/pharmacodynamic modelling data suggest that heavier patients may benefit from higher exposure to secukinumab through an increased dosing frequency [300 mg every 2 weeks (Q2W) vs. every 4 weeks (Q4W)]. What does this study add? Over 52 weeks, secukinumab 300 mg Q2W demonstrated superior efficacy compared with secukinumab 300 mg Q4W in patients with moderate-to-severe plaque psoriasis weighing ≥90 kg, with comparable safety results, consistent with the established secukinumab safety profile. In patients who did not achieve PASI 90 at week 16 on the Q4W regimen, uptitration to the Q2W regimen at week 16 resulted in improved efficacy responses through week 52 after switching.