Efficacy of Subcutaneous Secukinumab in Patients with Active Psoriatic Arthritis Stratified by Prior Tumor Necrosis Factor Inhibitor Use: Results from the Randomized Placebo-controlled FUTURE 2 Study

Patients and study design

FUTURE 2 is a 5-year, randomized, double-blind, multicenter, placebo-controlled, parallel-group study that is ongoing at the time of this analysis. Detailed patient eligibility criteria and study design have been reported previously⁶. Briefly, patients were ≥ 18 years old and had PsA fulfilling the ClASsification criteria for Psoriatic ARthritis (CASPAR) and active disease, defined as ≥ 3 tender and ≥ 3 swollen joints, despite previous treatment with conventional therapy. Patients were excluded if they had previously received biologics other than TNFi, or had received > 3 TNFi. Where applicable, TNFi were discontinued for 4–10 weeks before randomization. Concomitant methotrexate (MTX; ≤ 25 mg per week) was permitted.

Eligible patients were randomized (1:1:1:1) to receive subcutaneous (sc) doses of secukinumab 300 mg, 150 mg, 75 mg, or placebo at baseline, weeks 1, 2, 3, and 4, and every 4 weeks thereafter. At Week 16, placebo-treated patients were re-randomized (1:1) to receive secukinumab 300 mg or 150 mg sc from Week 16 (if they had < 20% improvement from baseline in tender and swollen joint counts) or Week 24. Randomization was stratified by previous TNFi use, with patients being TNFi-naive or TNFi-exposed (defined as having active disease despite having received an approved dose of a TNFi for ≥ 3 months or as having stopped treatment owing to safety and tolerability reasons).

The study was conducted in accordance with the Declaration of Helsinki principles and was approved by institutional review boards or independent ethics committees. Written informed consent was obtained from all patients.

Efficacy outcomes

Primary and secondary efficacy endpoints in the overall study population have been published⁶. Efficacy outcomes included proportion of patients with ≥ 20%, ≥ 50% or ≥ 70% improvement in American College of Rheumatology response criteria (ACR20, ACR50, and ACR70 responses, respectively); proportion of patients with ≥ 75% or ≥ 90% improvement in Psoriasis Area and Severity Index score (PASI75 and PASI90 responses, respectively: evaluated in patients with ≥ 3% body surface area affected with psoriasis); change in 28-joint Disease Activity Score using C-reactive protein (DAS28-CRP); physical component summary score of the Medical Outcomes Study Short Form-36 health survey (SF36-PCS); Health Assessment Questionnaire–Disability Index (HAQ-DI); resolution of dactylitis and enthesitis among patients with these symptoms at baseline.

Assessment of efficacy in TNFi-naive and TNFi-exposed patients was prespecified, with analyses performed by intent-to-treat. Exploratory posthoc analyses were performed in TNFi-naive and TNFi-exposed patients based on concomitant MTX use, baseline weight (≥ 90 kg and < 90 kg), and disease activity (DAS28-CRP > 5.1 and ≤ 5.1).

Statistical analysis

Sample size calculations and analysis of primary and other efficacy endpoints have been reported⁶. For binary variables, patients with missing values and those with < 20% improvement in tender and swollen joint counts at Week 16 were imputed as nonresponders in the Week 24 analyses (nonresponder imputation). P values were computed for comparisons of secukinumab doses versus placebo from a logistic regression model with treatment and previous TNFi use as factors and the covariate being baseline weight. Baseline PASI score was a covariate in PASI75 and PASI90 analyses. For continuous variables at Week 24, a mixed-effect model repeated measures model was used, with treatment regimen, analysis visit, and previous TNFi use as factors, and weight and baseline score as continuous covariates.

Efficacy analyses at Week 52 are presented for patients originally randomized to secukinumab. Both imputed analyses and descriptive summaries (observed data) were performed on efficacy endpoints at Week 52.