Discriminant capacity of clinical efficacy and nonsteroidal antiinflammatory drug-sparing endpoints, alone or in combination, in axial spondyloarthritis

Abstract

Objective. Using data from a randomized, double-blind, placebo-controlled study, we assessed the capacity of clinical and nonsteroidal antiinflammatory drug (NSAID)-sparing endpoints, alone and in combination, to discriminate between treatment effects in axial spondyloarthritis (axSpA). Methods. Patients with active NSAID-resistant axSpA received etanercept (ETN) 50 mg/week or placebo for 8 weeks and tapered/discontinued NSAID. In posthoc logistic regression analyses, OR were calculated that indicated the capacity of the following endpoints to discriminate between the effects of ETN and placebo at Week 8: Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 50; BASDAI ≤ 3; Assessment of Spondyloarthritis international Society (ASAS) 20; ASAS40; Ankylosing Spondylitis Disease Activity Score (ASDAS) with C-reactive protein (CRP) < 1.3 and ASDAS-CRP < 2.1; ≥ 50% decrease from baseline in ASAS-NSAID score, score < 10, and score = 0; and each clinical and/or each NSAID measure. Results. In 90 randomized patients (ETN, n = 42; placebo, n = 48), disease activity was similar between groups at baseline: mean (± SD) BASDAI (ETN vs placebo) 6.0 ± 1.6 versus 5.9 ± 1.5. NSAID intake was high: ASAS-NSAID score 98.2 ± 39.0 versus 93.0 ± 23.4. OR ranged from 1.6 (95% CI 0.5-5.4) for ASDAS-CRP < 1.3 to 5.8 (95% CI 1.2-29.1) for BASDAI50 and NSAID score of 0; most measures (34/45) reached statistical significance (α = 0.05) favoring ETN. Most combined outcome variables using OR were more discriminant than single outcome measures. Conclusion. These findings suggest that changes in NSAID intake during treatment do not prevent demonstration of clinically relevant effects of biologic treatment, and combined (i.e., clinical with NSAID-sparing) endpoints were frequently more discriminant than single (i.e., clinical) endpoints. ClinicalTrials.gov (NCT01298531).