POS0683 NOVEL STRINGENT OUTCOME MEASURES APPLIED TO THE PHASE 2 AND 3 ANIFROLUMAB TRIALS
Authors: Isenberg D. , Bruce I. N. , Furie R. , Morand E. F. , Tanaka Y. , Manzi S. , Kalunian K. , Psachoulia K. , Maho E. , Tummala R. 
Published: May 2021

Background:Patients with systemic lupus erythematosus (SLE) who received anifrolumab, a type I interferon receptor antibody, had greater BILAG–based Composite Lupus Assessment (BICLA) response rates vs placebo at Week (W)52 in the phase 2 MUSE1 and the phase 3 TULIP-12 and TULIP-23 trials. Patients receiving anifrolumab also had fewer flares, and more patients were able to taper glucocorticoids (GC) vs placebo.1–3Objectives:To evaluate anifrolumab treatment response vs placebo in patients with SLE from MUSE, TULIP-1, and TULIP-2 using more stringent BICLA definitions, as well as a novel endpoint that requires dual BICLA and SLE Responder Index (SRI[4]) responses.Methods:MUSE (NCT01438489), TULIP-1 (NCT02446912), and TULIP-2 (NCT02446899) were randomized, placebo-controlled, 52-week trials of intravenous anifrolumab (every 4 weeks for 48 weeks) in patients with moderate to severe SLE despite standard therapy.1–3 Sustained GC taper was defined as taper to ≤7.5 mg/day in patients receiving GC ≥10 mg/day at baseline, or to less than or equal to baseline dose in patients receiving GC <10 mg/day at baseline, achieved by W40 and sustained through W52. Response rates were compared between anifrolumab 300 mg vs placebo groups for patients who 1) attained a W52 BICLA response with sustained GC taper; 2) attained a W52 BICLA response and no flares after W12 (flare defined as ≥1 new BILAG-2004 A or ≥2 new BILAG-2004 B scores vs the prior visit); 3) attained a W52 BICLA response with sustained GC taper and no flares after W12; 4) attained an enhanced BICLA (eBICLA) response at W52 that required complete resolution of all baseline BILAG-2004 activity (all baseline A/B scores to D; no worsening of C or D scores); and 5) met both BICLA and SRI(4) response criteria.Results:Evaluated patients received anifrolumab 300 mg (MUSE, n=99; TULIP-1 and TULIP-2, n=180) or placebo (MUSE, n=102; TULIP-1, n=184; TULIP-2, n=182). Response rate differences favoring anifrolumab 300 mg over placebo were observed for all 5 endpoints across MUSE, TULIP-1, and TULIP-2 (Figure 1). A greater proportion of patients had BICLA responses at W52 with sustained GC taper with anifrolumab vs placebo. More patients had BICLA responses at W52 with no flares after W12 with anifrolumab vs placebo. More patients had BICLA responses at W52 with both sustained GC taper and no flares after W12 with anifrolumab vs placebo (treatment difference, 15.3%–19.3%; nominal P≤0.006). More patients attained eBICLA responses (requiring complete resolution of baseline disease activity) at W52 with anifrolumab vs placebo (treatment difference, 11.1%–14.1%; nominal P≤0.017). In addition, more patients were dual BICLA and SRI(4) responders at W52 with anifrolumab vs placebo (treatment difference, 14.3%–28.6%; nominal P≤0.004).Conclusion:In phase 2 and 3 trials in patients with SLE, anifrolumab treatment was consistently associated with improved disease control vs placebo using stringent endpoint definitions, including BICLA response with sustained GC taper and no flares, an enhanced BICLA response requiring complete resolution of baseline disease activity, and dual BICLA and SRI(4) responses.References:[1]Furie R, et al. Arthritis Rheumatol. 2017;69:376–86.[2]Furie RA, et al. Lancet Rheumatol. 2019;1:e208–19.[3]Morand EF, et al. N Engl J Med. 2020;382:211–21.Acknowledgements:Writing assistance by Rosie Butler, PhD, of JK Associates Inc., part of Fishawack Health. This study was sponsored by AstraZeneca.Disclosure of Interests:David Isenberg Consultant of: AstraZeneca, Celgene, Merck Serono, UCB, and Servier, Ian N. Bruce Speakers bureau: AstraZeneca, GSK, and UCB, Consultant of: Eli Lilly, GSK, ILTOO, Merck Serono, and UCB, Grant/research support from: Genzyme/Sanofi, GSK, Roche, and UCB, Richard Furie Consultant of: AstraZeneca, Grant/research support from: AstraZeneca, Eric F. Morand Speakers bureau: AstraZeneca, Consultant of: AstraZeneca, Grant/research support from: AstraZeneca, Yoshiya Tanaka Speakers bureau: AbbVie, Asahi Kasei, Astellas, Bristol Myers Squibb, Chugai, Daiichi-Sankyo, Eisai, Eli Lilly, Gilead, GSK, Janssen, Mitsubishi-Tanabe, Novartis, Pfizer, Sanofi, and YL Biologics, Grant/research support from: AbbVie, Chugai, Daiichi-Sankyo, Eisai, Mitsubishi-Tanabe, Takeda, and UCB, Susan Manzi Consultant of: AstraZeneca, Grant/research support from: AstraZeneca, Kenneth Kalunian Consultant of: AstraZeneca, Konstantina Psachoulia Employee of: AstraZeneca, Emmanuelle Maho Employee of: AstraZeneca, Raj Tummala Employee of: AstraZeneca