Background/Purpose: Since interleukin (IL)-17A has a potential role in the pathogenesis and chronic inflammation of psoriatic disease, with similar pathways impacting skin and joints, strategies aimed at blocking IL-17A may be beneficial in the treatment of psoriasis and psoriatic arthritis (PsA). Secukinumab (AIN457) is a fully human anti-IL-17A monoclonal antibody.

Methods: A total of 738 subjects aged ≥18 years with moderate-to-severe plaque psoriasis (incl. Psoriasis Area and Severity Index (PASI) score ≥12) were randomized 1:1:1 to subcutaneous secukinumab 150 mg or 300 mg or placebo given at randomization, Weeks 1, 2, and 3, followed by dosing every four weeks starting at Week 4 through Week 48. At Week 12, subjects not achieving a PASI 75 response were re-randomized 1:1 to secukinumab 150 mg or 300 mg. A pre-specified subanalysis of PASI responses and changes from baseline in the Health Assessment Questionnaire–Disability Index (HAQ-DI) up to Week 52 in subjects with concomitant PsA at baseline is reported here.  

Results: Baseline PASI and HAQ-DI scores were balanced across treatments. In 171 subjects with concomitant PsA, PASI 75 responses at Week 12 were 70% in the 150 mg group and 68% in the 300 mg group  (4%, placebo); PASI 90 responses were 44% and 53% in the 150 mg and 300 mg groups, respectively (0%, placebo). PASI 75 responses (61%, 150 mg; 68%, 300 mg) and PASI 90 responses (37%, 150 mg; 56%, 300 mg) were maintained up to one year (Fig 1). Physical function as measured by HAQ-DI change from baseline was significantly greater at Weeks 4 and 12 with 300 mg vs placebo (P < 0.05). HAQ –DI responses were more pronounced in patients with more disability. In patients with baseline HAQ-DI ≥0.5, reduction in HAQ-DI score was statistically significantly greater for 150 mg at Week 12 and for 300 mg at Weeks 4 and 12 vs placebo (Fig 2) and responses continued up to Week 52. Secukinumab was well tolerated with no unexpected safety findings.

Conclusion: In subjects with psoriasis and concomitant PsA, secukinumab was associated with superior improvement in skin symptoms and physical functioning compared with placebo. These data strongly support continued evaluation of secukinumab in patients with PsA.

Figure 1. PASI 75/90 Response at Weeks 12 and 52 

All PsA Patients (Non-Responder Imputation)

Figure 2. Change from Baseline in HAQ-DI Score to Week 12

Placebo-comparison (LOCF) for patients with baseline HAQ-DI ≥0.5