Interleukin-17A ( IL-17A ) is a key cytokine in the pathogenesis of psoriatic disease of the skin and joints. In phase 3 trials, Secukinumab ( Cosentyx ), a fully human anti-IL-17A monoclonal antibody, has demonstrated robust efficacy in psoriasis, with rapid onset, high response rates, and durable response.
The aim of the study was to evaluate the efficacy of Secukinumab in subjects with psoriasis and concomitant psoriatic arthritis ( PsA ) with respect to psoriasis symptoms and physical function.
Researchers conducted pre-specified subanalyses of the phase 3 FIXTURE and ERASURE trials.
The 52-week FIXTURE and ERASURE trials randomized subjects with moderate-to-severe plaque psoriasis to subcutaneous Secukinumab [ Cosentyx ] 300 or 150 mg ( baseline, weeks 1, 2, 3, every 4 weeks from week 4 until week 48 ), Etanercept [ Enbrel ] 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 psoriatic arthritis ( n=196, FIXTURE; n=171, ERASURE ).
Physical functioning ( mean change from baseline in HAQ-DI ) was greater with Secukinumab 300 mg versus 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 greater than or equal to 0.5 ).
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 less than 0.0001 ) and with Secukinumab 300 mg vs Etanercept ( 72% vs 39%; P=0.0084 ).
In conclusion, Secukinumab 300 mg produced significant improvement in psoriasis and physical functioning in subjects with concomitant psoriatic arthritis. ( Xagena )
Gottlieb AB et al, J Drugs Dermatol 2015;14:821-833