Anifrolumab efficacy and safety by type I interferon gene signature and clinical subgroups in patients with SLE: post hoc analysis of pooled data from two phase III trials. Issue 7 (25th March 2022)

• Record Type: Journal Article
• Authors: Vital, Edward M; Merrill, Joan T; Morand, Eric F; Furie, Richard A; Bruce, Ian N; Tanaka, Yoshiya; Manzi, Susan; Kalunian, Kenneth C; Kalyani, Rubana N; Streicher, Katie; Abreu, Gabriel; Tummala, Raj
• Is Part Of: Annals of the rheumatic diseases. Volume 81:Issue 7(2022)
• Page Start: 951
• Page End: 961
• Publication Date: 2022-03-25
• Subjects: biological therapy -- lupus erythematosus -- systemic -- therapeutics; Rheumatism -- Periodicals; 616.723005
• DOI: 10.1136/annrheumdis-2021-221425
• Languages: English
• ISSNs: 0003-4967

Abstract

Abstract : Objectives: To characterise the efficacy and safety of anifrolumab in patients with systemic lupus erythematosus (SLE) according to interferon gene signature (IFNGS), demographic and clinical subgroups. Methods: We performed post hoc analyses of pooled data from the 52-week phase III TULIP-1/TULIP-2 placebo-controlled trials of intravenous anifrolumab in moderate-to-severe SLE. Outcomes were assessed in predefined subgroups: IFNGS (high/low), age, sex, body mass index, race, geographic region, age of onset, glucocorticoid use, disease activity and serological markers. Results: In pooled data, patients received anifrolumab 300 mg (360/726) or placebo (366/726); 82.6% were IFNGS-high. IFNGS-high patients had greater baseline disease activity and were more likely to have abnormal serological markers versus IFNGS-low patients. In the total population, a greater proportion of patients treated with anifrolumab versus placebo achieved British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) response at week 52 (difference 16.6%; nominal p<0.001). BICLA response treatment differences with anifrolumab versus placebo were comparable to the total population across most predefined subgroups, including subgroups for baseline glucocorticoid dosage (<10/≥10 mg/day prednisone/equivalent) and for clinical disease activity (SLE Disease Activity Index 2000 score <10/≥10). Subgroups with larger treatment differences included IFNGS-high patients (18.2%), patients with abnormal baseline serological markers (23.1%) and Asian patients (29.2%). The safety profile of anifrolumab was similar across subgroups. Conclusions: Overall, this study supports the consistent efficacy and safety of anifrolumab across a range of patients with moderate-to-severe SLE. In a few subgroups, small sample sizes limited conclusions from being drawn regarding the treatment benefit with anifrolumab. Trial registration number: NCT02446912, NCT02446899 .