Background: Interleukin (IL)-17A is a key cytokine in the pathogenesis of psoriatic disease of the skin and joints. In phase 3 trials, secukinumab, a fully human anti-IL-17A monoclonal antibody, demonstrated robust efficacy in psoriasis, with rapid onset, high response rates, and durable response.
Objective: To evaluate the efficacy of secukinumab in subjects with psoriasis and concomitant psoriatic arthritis (PsA) with respect to psoriasis symptoms and physical function, we conducted pre-specified subanalyses of the phase 3 FIXTURE and ERASURE trials.
Methods: The 52-week FIXTURE and ERASURE trials randomized subjects with moderate-to-severe plaque psoriasis to subcutaneous secukinumab 300 or 150 mg (Baseline, weeks 1, 2, 3, every 4 weeks from week 4 until week 48), etanercept 50 mg (twice weekly through week 12, once weekly thereafter through week 51; FIXTURE only), or placebo. In this analysis, changes in Health Assessment Questionnaire-Disability Index (HAQ-DI) and PASI 75 responses were assessed in subpopulations with concomitant PsA (n=196, FIXTURE; n=171, ERASURE).
Results: Physical functioning (mean change from Baseline in HAQ-DI) was greater with secukinumab 300 mg vs. placebo at week 12 in both trials (FIXTURE, -0.41 vs. 0.02/P=0.0001; ERASURE, -0.35 vs. -0.08/P=0.0003); corresponding values were -0.29 for etanercept and -0.19 for secukinumab 150 mg in FIXTURE and -0.18 for secukinumab 150 mg in ERASURE. Greater responses were seen in subjects with greater Baseline disability (HAQ-DI ≥05). Week 12 PASI 75 responses were higher with secukinumab 300 mg/150 mg vs. placebo in FIXTURE (72%/59% vs. 2%) and ERASURE (68%/70% vs. 4%; all P<0.0001) and with secukinumab 300 mg vs. etanercept (72% vs 39%; P=0.0084).
Conclusion: Secukinumab 300 mg produced significant improvement in psoriasis and physical functioning in subjects with concomitant PsA. ClinicalTrials.gov numbers: NCT01358578 (FIXTURE); NCT01365455 (ERASURE)