175 Comparative effectiveness of secukinumab and infliximab in psoriatic arthritis assessed by matching-adjusted indirect comparison using pivotal Phase III clinical trial data

Abstract

Background: Therapeutic options with discrete modes of action are now available for psoriatic arthritis (PsA). Clinicians require evidence to guide decision‐making. No head‐to‐head randomised clinical trials have compared secukinumab 150mg (anti‐interleukin‐17A) with infliximab 5 mg/kg (TNF inhibitor [TNFi]) in patients with PsA. Matching‐adjusted indirect comparison (MAIC) can estimate comparative effectiveness and enables treatment outcomes to be compared across effectively balanced trial populations. MAIC, was used to assess the comparative effectiveness of secukinumab and infliximab for up to one year using pooled FUTURE 1 and FUTURE 2 individual patient data (IPD) and published aggregate IMPACT 2 data, respectively. Methods: Pooled FUTURE 1 and FUTURE 2 data were used to maximise the effective sample size (ESS) for secukinumab. IPD from the secukinumab arms of FUTURE 1 and FUTURE 2 (n=302) were weighted to match selected baseline characteristics of the infliximab arm of IMPACT 2 (n=100). Placebo arms were also matched; placebo‐adjusted comparisons were possible only until week 16 because patients could receive active treatment from this timepoint onwards. Logistic regression was used to determine weights for age, sex, race, bodyweight, methotrexate use, presence of psoriasis (≤3% body surface area), mean psoriasis area and Severity Index and Health Assessment Questionnaire‐Disability Index scores, dactylitis, enthesitis, and previous TNFi therapy. Recalculated outcomes from FUTURE 1 and 2 (secukinumab, ESS=91; placebo, ESS=59) were compared with data from IMPACT 2 (infliximab, n=100; placebo, n=100). Pairwise comparisons using odds ratios (ORs [95% CIs]) were performed for American College of Rheumatology (ACR) 20, 50 and 70 responses at nearest‐equivalent timepoints across trials: weeks 6/ 8, 14/16, 24, and 54/52. Mean changes from baseline in Short Form‐36 (SF‐36) Physical and Mental Component Summary (MCS) scores were also compared. Strict thresholds were avoided when interpreting P values, in line with American Statistical Association guidance. Results: There was no evidence of differences in ACR 20, 50 and 70 responses between secukinumab and infliximab at weeks 6/8, 14/16 (placebo‐adjusted), and 24 (non‐placebo‐adjusted). At week 54/52, ACR 20 and 50 responses were higher with secukinumab than infliximab (OR [95% CI]: 4.05 [1.98, 8.30], p<0.001 and 1.90 [1.05, 3.44], p=0.034, respectively). Improvements in SF‐36 MCS scores were greater with secukinumab than infliximab at weeks 14/16 (p=0.063), 24 (p=0.001), and 54/52 (p<0.001). A sensitivity analysis that added PsA duration, swollen joint count and CRP levels to the matching parameters yielded similar results. Conclusion: In this MAIC, secukinumab showed evidence of superiority for symptomatic improvement (ACR 20 and 50) over infliximab for active PsA at one year, accompanied by greater improvements in SF‐36 MCS. At earlier timepoints, there was no evidence of differences in ACR responses between secukinumab and infliximab.