Propensity score matching/reweighting analysis comparing intravenous golimumab to infliximab for ankylosing spondylitis using data from the GO-ALIVE and ASSERT trials.

OBJECTIVE: To compare the relative efficacy of intravenous golimumab (GOL IV) and infliximab (IFX) for active ankylosing spondylitis (AS). METHODS: Propensity score (PS) methods were used to compare the efficacy of GOL IV 2 mg/kg and IFX 5 mg/kg using individual patient data (IPD) from the active arms of the phase 3 GO-ALIVE and ASSERT studies. Outcomes included the proportion of patients with a ≥ 20% improvement in the Assessment of Spondyloarthritis International Society Criteria (ASAS20), change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) score, and change from baseline in C-reactive protein (CRP) levels from weeks 4-52. RESULTS: Before matching, 105 patients were treated with GOL IV and 201 patients were treated with IFX. After matching on all covariates, 118 patients were included in the ASAS20 analysis, 96 in the BASFI analysis, and 160 in the CRP analysis. After matching, GOL IV showed significantly greater improvement in ASAS20 response than IFX for weeks 28-44 (e.g., OR = 9.05 [95% CI 1.62-50.4] at week 44) and was comparable in change from baseline in BASFI scores and CRP levels to IFX at all time points. Results were robust for inclusion of different sets of covariates in scenario analyses. CONCLUSIONS: This is the first analysis of its kind to leverage clinical trial data to compare two biologics using PS methods in the treatment of active AS. Overall, GOL IV was associated with greater improvement in ASAS20 response than IFX in patients with AS at 28, 36, and 44 weeks of follow-up. Key Points • Although intravenous golimumab (GOL IV) and infliximab (IFX) are the only two IV-based tumor necrosis factor (TNF) inhibitors with demonstrated phase 3 clinical efficacy in patients with ankylosing spondylitis (AS), no study has evaluated their comparative efficacy in a head-to-head trial. • Propensity score matching was used to derive indirect treatment comparisons of GOL IV and IFX for ≥ 20% in the Assessment of Spondyloarthritis International Society Criteria (ASAS20), change in Bath Ankylosing Spondylitis Functional Index (BASFI), and change in C-reactive protein (CRP) using individual patient data from the GO-ALIVE and ASSERT phase 3 trials. • Propensity score matched indirect comparisons showed improved relative efficacy of GOL IV compared to IFX; after matching for up to 16 baseline covariates, GOL IV was associated with significantly greater odds of ASAS20 response at weeks 28, 36, and 44 than IFX as well as equivalent changes from baseline in BASFI and CRP. • This novel application of propensity score matching using data from phase 3 trials, the first analysis of its kind in AS, allowed adjustment for important imbalances in prognostic factors between trials to generate estimates of comparative efficacy between GOL IV and IFX in the absence of a head-to-head trial between these treatments.

A systematic review and network meta-analysis of current and investigational treatments for active ankylosing spondylitis.

OBJECTIVE: To compare the relative efficacy of current and investigational biologic and oral small molecule (OSM) treatments for active ankylosing spondylitis (AS). METHODS: A systematic literature review was conducted to identify all phase 2/3 randomized trials of interest in patients with AS. Outcomes assessed were ≥ 20% improvement in the Assessment of Spondyloarthritis International Society Criteria (ASAS20) and change from baseline in Bath Ankylosing Spondylitis Functional Index (BASFI) and C-reactive protein (CRP) at weeks 12-16. Bayesian network meta-analyses were conducted for outcomes using a random effects model. Baseline-risk adjustment was also conducted to account for differences in placebo response across studies. Surface Under the Cumulative Ranking curve (SUCRA) values are reported, reflecting the relative probability that intervention was the best of all interventions. RESULTS: The investigational agent tofacitinib 5 mg was the top-ranked treatment (SUCRA, 93%) for ASAS20 response, followed by intravenous (IV) golimumab 2 mg/kg (90%). Golimumab IV 2 mg/kg and infliximab 5 mg/kg were the top two ranked treatments for change from baseline in BASFI (golimumab IV, 81%; infliximab, 80%) and change from baseline in CRP (infliximab, 90%; golimumab IV, 82%). CONCLUSIONS: Two approved therapies (golimumab IV, infliximab) and one investigational product ranked highest for efficacy in AS. Key Points • Although golimumab IV, infliximab, and tofacitinib ranked highest for efficacy in AS, differences in efficacy between approved and investigational therapies were not statistically significant.