Concordance and discordance in SLE clinical trial outcome measures: analysis of three anifrolumab phase 2/3 trials

ObjectivesIn the anifrolumab systemic lupus erythematosus (SLE) trial programme, there was one trial (TULIP-1) in which BILAG-based Composite Lupus Assessment (BICLA) responses favoured anifrolumab over placebo, but the SLE Responder Index (SRI(4)) treatment difference was not significant. We investigated the degree of concordance between BICLA and SRI(4) across anifrolumab trials in order to better understand drivers of discrepant SLE trial results.MethodsTULIP-1, TULIP-2 (both phase 3) and MUSE (phase 2b) were randomised, 52-week trials of intravenous anifrolumab (300 mg every 4 weeks, 48 weeks; TULIP-1/TULIP-2: n=180; MUSE: n=99) or placebo (TULIP-1: n=184, TULIP-2: n=182; MUSE: n=102). Week 52 BICLA and SRI(4) outcomes were assessed for each patient.ResultsMost patients (78%–85%) had concordant BICLA and SRI(4) outcomes (Cohen’s Kappa 0.6–0.7, nominal pConclusionsAcross trials, most patients had concordant BICLA/SRI(4) outcomes and dual BICLA/SRI(4) responses favoured anifrolumab. A BICLA non-responder/SRI(4) responder subgroup was identified where imbalances of key factors driving the BICLA/SRI(4) discordance (disease activity, glucocorticoid taper) disproportionately favoured the TULIP-1 placebo group. Careful attention to baseline disease activity and monitoring glucocorticoid taper variation will be essential in future SLE trials.Trial registration numbersNCT02446912andNCT02446899.