OP0049 EFFICACY OF ANIFROLUMAB IN ACTIVE SYSTEMIC LUPUS ERYTHEMATOSUS: PATIENT SUBGROUP ANALYSIS OF BICLA RESPONSE IN 2 PHASE 3 TRIALS
Authors: E. F. Morand, R. Furie, Y. Tanaka, R. Kalyani, G. Abreu, L. Pineda, R. Tummala
Journal: Annals of the Rheumatic Diseases (2020)

Background: Treatment of patients with systemic lupus erythematosus (SLE) with the type I interferon (IFN) receptor inhibitor anifrolumab resulted in higher British Isles Lupus Assessment Group (BILAG)–based Composite Lupus Assessment (BICLA) response rates vs placebo at Week 52 in the phase 3 randomized trials, TULIP-2 (primary endpoint; 16.3% difference) 1 and TULIP-1 (secondary endpoint; 16.4% difference). 2 BICLA is a validated composite global disease measure that registers both partial and complete improvement within organ systems. Objectives: TULIP-2 and TULIP-1 data were analyzed to evaluate BICLA responses to anifrolumab vs placebo at Week 52 in protocol-defined subgroups of patients with active SLE. Methods: TULIP-2 and TULIP-1 were randomized, double-blind, placebo-controlled trials that evaluated efficacy and safety of intravenous anifrolumab vs placebo administered every 4 weeks, with the primary endpoints assessed at Week 52, in patients with moderate to severe SLE despite standard-of-care treatment. 1,2 BICLA responses are defined by all of the following: reduction of baseline BILAG-2004 A and B domain scores to B/C/D and C/D, respectively, and no worsening in any organ system; no worsening of the SLE Disease Activity Index 2000 (SLEDAI-2K) score; no worsening of ≥0.3 points in the Physician’s Global Assessment (range 0–3); no trial treatment discontinuation; and no use of medications restricted by the protocol. 3 BICLA responses were compared between anifrolumab 300 mg and placebo groups, and robustness of BICLA responses was assessed across protocol-defined subgroups. TULIP-1 data were analyzed incorporating the amended restricted medication rules, as described. 2 Results: In TULIP-2 and TULIP-1, 180 patients in each trial received anifrolumab 300 mg (182 and 184 patients received placebo, respectively). Baseline demographics, disease characteristics, and standard-of-care medications were balanced between anifrolumab and placebo groups within both TULIP trials. Patients in TULIP-2 and TULIP-1 had comparable BICLA responses ( Figure ). Across multiple subgroups, higher percentages of patients achieved BICLA responses at Week 52 in the anifrolumab vs placebo arms ( Figure ). There was concordance of BICLA responses favoring anifrolumab across the protocol-defined subgroups of baseline disease severity (SLEDAI-2K &lt;10 points [difference 15.3%, TULIP-2; 16.9%, TULIP-1] vs ≥10 points [difference 16.7%, TULIP-2; 17.1%, TULIP-1]) and baseline oral corticosteroid use (prednisone or equivalent &lt;10 mg/d [difference 20.1%, TULIP-2; 16.2%, TULIP-1] vs ≥10 mg/d [difference 12.0%, TULIP-2; 17.7%, TULIP-1]). Numerically different BICLA effect sizes between the anifrolumab vs placebo arms were observed in both studies in relation to baseline IFN gene signature status (high [difference 17.3%, TULIP-2; 19.1%, TULIP-1] vs low [difference 11.2%, TULIP-2; 7.5%, TULIP-1]). Other subgroups including age, sex, age at onset, race, and anti-drug antibody status showed similar uniformity of response. Conclusion: The uniformity of robust BICLA response rates across prespecified subgroups in both phase 3 trials shows consistent clinical benefit of anifrolumab irrespective of patient baseline characteristics. However, given the small patient numbers in some subgroups, these results should be interpreted with caution. References: [1]Morand EF, et al. N Engl J Med. 2020;382:211–221. [2]Furie RA, et al. Lancet Rheumatol . 2019;1:e208–e219. [3]Wallace DJ, et al. Ann Rheum Dis. 2014;73:183–190. Disclosure of Interests: Eric F. Morand Grant/research support from: AstraZeneca, Consultant of: AstraZeneca, Speakers bureau: AstraZeneca, Richard Furie Grant/research support from: AstraZeneca, Biogen, Consultant of: AstraZeneca, Biogen, Yoshiya Tanaka Grant/research support from: Asahi-kasei, Astellas, Mitsubishi-Tanabe, Chugai, Takeda, Sanofi, Bristol-Myers, UCB, Daiichi-Sankyo, Eisai, Pfizer, and Ono, Consultant of: Abbvie, Astellas, Bristol-Myers Squibb, Eli Lilly, Pfizer, Speakers bureau: Daiichi-Sankyo, Astellas, Chugai, Eli Lilly, Pfizer, AbbVie, YL Biologics, Bristol-Myers, Takeda, Mitsubishi-Tanabe, Novartis, Eisai, Janssen, Sanofi, UCB, and Teijin, Rubana Kalyani Employee of: AstraZeneca, Gabriel Abreu Employee of: AstraZeneca, Lilia Pineda Employee of: AstraZeneca, Raj Tummala Employee of: AstraZeneca