POS0691\u2005EFFECTS OF ANIFROLUMAB ON RENAL DISEASE IN PATIENTS WITH SLE

Abstract

The type I interferon (IFN) receptor antibody anifrolumab has shown efficacy in patients with systemic lupus erythematosus (SLE) in the phase 3 TULIP-1 and TULIP-2 trials.1,2 Type I IFN dysregulation is associated with lupus nephritis (LN) pathogenesis.3Pooled TULIP data were analyzed post hoc to assess baseline characteristics of patients with and without renal involvement and to evaluate the effects of anifrolumab on renal disease.TULIP-1 (NCT02446912) and TULIP-2 (NCT02446899) were randomized, placebo-controlled, 52-week trials of intravenous anifrolumab every 4 weeks in patients with moderate to severe SLE despite standard therapy, which excluded patients with severe active LN.1,2 Renal involvement at baseline was defined as any of the following: BILAG-2004 renal score A–C; SLEDAI-2K renal score >0; urine protein–creatinine ratio (UPCR) >0.5\u2009mg/mg. Baseline characteristics were evaluated in patients with and without renal involvement, and the following endpoints were compared for the anifrolumab 300\u2009mg and placebo groups: cumulative UPCR (area under the curve, AUC) through Week (W)52; percentage of patients with UPCR >0.5\u2009mg/mg at baseline who improved to UPCR ≤0.5\u2009mg/mg at W52; percentage of patients with renal flares (new BILAG-2004 A/B renal score vs prior visit); cumulative glucocorticoid (GC) use (AUC) through W52; and percentage changes in complement C3/C4 from baseline to W52.Of the 726 patients in TULIP-1/-2 (anifrolumab, n=360; placebo, n=366), 99 had renal involvement at baseline (anifrolumab, n=45; placebo, n=54), 57 of whom had UPCR >0.5\u2009mg/mg (anifrolumab, n=24; placebo, n=33). Patients with renal involvement vs without renal involvement had a lower mean age (37.8 vs 42.4 years) and were more likely to be male (14.1% vs 6.1%), Asian (16.2% vs 9.6%), IFN gene signature test–high (89.9% vs 81.5%), and anti-dsDNA positive (69.7% vs 40.4%); have a SLEDAI-2K score ≥10 (91.9% vs 68.4%); and be receiving GC ≥10\u2009mg/day (67.7% vs 49.1%) or mycophenolate (26.3% vs 11.5%) at baseline. Among patients with baseline renal involvement, anifrolumab treatment was associated with a numerically greater improvement vs placebo in cumulative UPCR (AUC) through W52 (LS mean difference [SE]: –54.1 [54.26]) (Table 1). Numerically more patients improved from UPCR >0.5\u2009mg/mg at baseline to ≤0.5\u2009mg/mg at W52 with anifrolumab vs placebo (difference [SE], 4.9% [13.3]). Among all TULIP patients, fewer had ≥1 BILAG-2004 renal flare with anifrolumab vs placebo (5.0% vs 7.4%).4 Among patients with renal involvement, cumulative GC use (AUC) through W52 was lower with anifrolumab vs placebo (LS mean difference [SE]: –210.3\u2009mg [332.6]) and there were numerically greater improvements in C3 and C4 from baseline to W52 (Table 1).TULIP data suggest renal benefit with anifrolumab in patients with SLE with mild/stable renal disease, supporting further investigation into anifrolumab’s efficacy in patients with active LN.[1]Furie R. Lancet Rheumatol. 2019;1:e208–19.[2]Morand E. N Engl J Med. 2020;382:211–21.[3]Feng X. Arthritis Rheum. 2006;54:2951–62.[4]Furie R [abstract]. Arthritis Rheumatol. 2020;72(supp 10).Table 1.Renal Endpoints in TULIP-1 and TULIP-2Endpoint (baseline to Week 52)PlaceboAnifrolumab 300 mgUPCR AUCan5445LS mean (SE)271.8 (54.8)217.7 (60.0)LS mean difference (SE), 95% CI−54.1 (54.3), −161.9, 53.6Improvement from >0.5 to ≤0.5\u2009mg/mg UPCRbn3324Patients with improvement (%)36.341.2Difference, % (SE), 95% CI4.9 (13.3), −21.1, 30.9Glucocorticoid AUCan5445LS mean (SE)3524.5 (339.0)3314.2 (365.2)LS mean difference (SE), 95% CI−210.3 (332.6), −870.7, 450.1Change in C3/C4 (%)cC3N3121Mean (SE)20.3 (6.2)26.6 (5.0)C4N1914Mean (SE)29.1 (12.0)38.7 (13.8)AUC, area under the curve; CI, confidence interval; LS, least squares; UPCR, urine protein–creatinine ratio; SE, standard error.n, number satisfying baseline inclusion criteria for subgroup.aPatients with baseline renal involvement; analysis of covariance.bStratified Cochran–Mantel–Haenszel.cPatients with renal involvement and abnormal C3/C4 at baseline.Writing assistance by Rosie Butler, PhD, of JK Associates Inc. part of Fishawack Health. This study was sponsored by AstraZeneca.Eric F. Morand Speakers bureau: AstraZeneca, Consultant of: AstraZeneca, Grant/research support from: AstraZeneca, Richard Furie 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, Tsutomu Takeuchi Speakers bureau: AbbVie GK., Bristol–Myers K.K., Chugai Pharmaceutical Co,. Ltd., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Astellas Pharma Inc, Daiichi Sankyo Co., Ltd., Eisai Co., Ltd., Sanofi K.K., Teijin Pharma Ltd., Takeda Pharmaceutical Co., Ltd., Novartis Pharma K.K., Consultant of: AstraZeneca K.K., Eli Lilly Japan K.K., Novartis Pharma K.K., Mitsubishi Tanabe Pharma Co., Abbvie GK, Nipponkayaku Co.Ltd, Janssen Pharmaceutical K.K., Astellas Pharma Inc,. Taiho Pharmaceutical Co., Ltd., Chugai Pharmaceutical Co, Ltd., Grant/research support from: Astellas Pharma Inc, Chugai Pharmaceutical Co, Ltd., Daiichi Sankyo Co., Ltd., Takeda Pharmaceutical Co., Ltd., AbbVie GK, Asahikasei Pharma Corp., Mitsubishi Tanabe Pharma Co., Pfizer Japan Inc., Eisai Co., Ltd., AYUMI Pharmaceutical Corporation, Nipponkayaku Co.Ltd., Novartis Pharma K.K., Gabriel Abreu Employee of: AstraZeneca, Raj Tummala Employee of: AstraZeneca, Catharina Lindholm Employee of: AstraZeneca