Secukinumab improves active psoriatic arthritis symptoms and inhibits radiographic progression: primary results from the randomised, double-blind, phase III FUTURE 5 study

Abstract

Objectives: 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).

Methods: 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.

Results: 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 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.

Conclusion: 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.

Trial registration number: NCT02404350; Results.

Keywords: cytokines; dmards (biologic); psoriatic arthritis; treatment.

Figure 1

(A) ACR20, (B) ACR50 and (C) ACR70 response rates from baseline up to week 24^a in the overall population and by anti-TNF status. *P<0.0001; †p<0.001; §p<0.01; ‡p<0.05 unadjusted p values versus placebo (Statistical analysis was based on logistic regression. Missing values and placebo patients rescued at week 16 were imputed as non-responders.) ^aThe primary endpoint was ACR20 response in the overall population at week 16. ACR20/50/70, ≥20/50/70% improvement from baseline in American College of Rheumatology response criteria; anti-TNF-IR, intolerance or inadequate response to antitumour necrosis factor therapy.

Figure 2

Resolution of enthesitis and dactylitis in the overall population from baseline up to week 24^a.*P<0.0001; †p<0.001; §p<0.01; ‡p<0.05 unadjusted p values versus placebo. (Statistical analysis was based on logistic regression. Missing values and placebo patients rescued at week 16 were imputed as non-responders.) ^aResolution of dactylitis and enthesitis were not significant for secukinumab 150 mg without load in hierarchical testing.

Figure 3

Change in vdH-mTSS from baseline at week 24 (non-parametric ANCOVA-linear extrapolation in the overall population and by anti-TNF status. †P<0.001; §p<0.01; ‡p<0.05 unadjusted p values versus placebo (Statistical analysis was based on a non-parametric ANCOVA. Linear extrapolation was applied if a baseline and week 16 value were available). ANCOVA, analysis of covariance; anti-TNF-IR, intolerance or inadequate response to antitumour necrosis factor therapy; LD, loading dose; vdH-mTSS, van der Heijde-modified total Sharp score.