The study conducted to evaluate the effect of subcutaneous (s.c.) secukinumab, an interleukin-17A inhibitor, on clinical signs and symptoms and radiographic progression in patients with psoriatic arthritis (PsA)

Psoriatic arthritis (PsA) is a chronic, inflammatory disease characterized by peripheral arthritis, axial disease, dactylitis, enthesitis and skin and nail psoriasis. It can have a substantial impact on quality of life and work productivity, with many patients experiencing irreversible joint damage and disability. Indeed, bone erosions occur in approximately half of patients within 2 years.

Enhanced understanding of the pathophysiology of PsA has aided the development of targeted therapies to manage its signs and symptoms. The proinflammatory cytokine interleukin (IL)-17A mediates multiple biological functions that result in joint and entheseal inflammation, damage, and tissue remodeling, which are characteristic of PsA.

Recommendations from the European League Against Rheumatism (EULAR) and the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) recognize targeting IL-17A as a therapeutic strategy to manage all the main clinical domains of PsA.

Results

Adults (n=996) with active PsA were randomised 2:2:2:3 to s.c. Secukinumab 300 mg or 150 mg with loading dose (LD), 150 mg without LD or placebo. All groups received secukinumab or placebo at baseline, weeks 1, 2 and 3 and then every 4 weeks from week 4. The primary endpoint was the proportion of patients achieving an American College of Rheumatology 20 (ACR20) response at week 16.

Significantly more patients achieved an ACR20 response at week 16 with secukinumab 300 mg with LD (62.6%), 150 mg with LD (55.5%) or 150 mg without LD (59.5%) than placebo (27.4%) (p<0.0001 for all; non-responder imputation).

Radiographic progression, as measured by the van der Heijde-modified total Sharp score, was significantly inhibited at week 24 in all secukinumab arms versus placebo (p<0.01 for 300 mg with LD and 150 mg without LD and p<0.05 for 150 mg with LD; linear extrapolation).

Adverse event rates at week 24 were similar across treatment arms: 63.1% (300 mg with LD), 62.7% (150 mg with LD), 61.1% (150 mg without LD) and 62.0% (placebo). No deaths or new safety signals were reported

S.c. secukinumab 300 mg and 150 mg with and without LD significantly improved clinical signs and symptoms and inhibited radiographic structural progression versus placebo at week 24 in patients with PsA.