Efficacy of anifrolumab across organ domains in patients with moderate-to-severe systemic lupus erythematosus: a post-hoc analysis of pooled data from the TULIP-1 and TULIP-2 trials

Eric F Morand; Richard A Furie; Ian N Bruce; Edward M Vital; Maria Dall'Era; Emmanuelle Maho; Lilia Pineda; Raj Tummala

doi:10.1016/S2665-9913(21)00317-9

Efficacy of anifrolumab across organ domains in patients with moderate-to-severe systemic lupus erythematosus: a post-hoc analysis of pooled data from the TULIP-1 and TULIP-2 trials

Lancet Rheumatol. 2022 Apr;4(4):e282-e292. doi: 10.1016/S2665-9913(21)00317-9. Epub 2022 Feb 3.

Authors

Eric F Morand¹, Richard A Furie², Ian N Bruce³, Edward M Vital⁴, Maria Dall'Era⁵, Emmanuelle Maho⁶, Lilia Pineda⁷, Raj Tummala⁸

Affiliations

¹ Centre for Inflammatory Disease, Monash University, Melbourne, VIC, Australia.
² Division of Rheumatology, Zucker School of Medicine at Hofstra/Northwell, Great Neck, NY, USA.
³ Centre for Epidemiology Versus Arthritis, The University of Manchester and NIHR Manchester Biomedical Research Centre, Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK.
⁴ Leeds Institute of Rheumatic and Musculoskeletal Medicine, University of Leeds, Leeds, UK; NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds, UK.
⁵ Division of Rheumatology, University of California San Francisco, San Francisco, CA, USA.
⁶ BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK.
⁷ BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA.
⁸ BioPharmaceuticals R&D, AstraZeneca, Gaithersburg, MD, USA. Electronic address: raj.tummala@astrazeneca.com.

PMID: 38288923
DOI: 10.1016/S2665-9913(21)00317-9

Abstract

Background: Systemic lupus erythematosus (SLE) is a chronic autoimmune disease characterised by multisystem involvement. We aimed to evaluate the efficacy of anifrolumab on organ domain-specific SLE disease activity.

Methods: In this post-hoc analysis, data were pooled from the randomised, placebo-controlled, phase 3 TULIP-1 (NCT02446912) and TULIP-2 (NCT02446899) trials of anifrolumab (300 mg intravenously once every 4 weeks for 48 weeks) in patients aged 18-70 years with moderate-to-severe SLE. We evaluated changes from baseline to week 52 in British Isles Lupus Assessment Group 2004 (BILAG-2004) and SLE Disease Activity Index 2000 (SLEDAI-2K) organ domain scores, Cutaneous Lupus Erythematosus Disease Area and Severity Index activity score (CLASI-A), swollen and tender joint counts, haematology, and serology.

Findings: Among the 726 patients included, the mean age was 41·8 years (SD 11·9); 674 (93%) were female, 52 (7%) were male, and 479 (66%) were White. 360 patients received anifrolumab 300 mg (180 patients in each trial), and 366 received placebo (184 patients in TULIP-1 and 182 patients in TULIP-2). The most frequently affected organ domains at baseline were musculoskeletal (645 [89%] patients based on BILAG-2004; 684 [94%] with SLEDAI-2K) and mucocutaneous (627 [86%] with BILAG-2004; 699 [96%] based on SLEDAI-2K). At week 52, anifrolumab treatment resulted in greater improvements versus placebo in the musculoskeletal system (176 [56%] of 317 patients vs 143 [44%] of 328 with BILAG-2004; 164 [49%] of 335 vs 141 [40%] of 349 with SLEDAI-2K), the mucocutaneous system (168 [54%] of 315 vs 119 [38%] of 312 with BILAG-2004; 190 [55%] of 348 vs 138 [39%] of 351 SLEDAI-2K), and immunological system (44 [19%] of 237 vs 26 [11%] of 230 with SLEDAI-2K). Less frequently affected domains had varied responses. Among patients with a CLASI-A of 10 or more at baseline, greater proportions of patients receiving anifrolumab than placebo achieved a reduction of 50% or more in CLASI-A at week 52 (49 [46%] of 107 vs 24 [25%] of 94). Among patients with at least six swollen joints, more patients in the anifrolumab group than in the placebo group had a 50% or more reduction from baseline to week 52 in swollen joint count (99 [57%] of 174 vs 92 [46%] of 200), but the difference between groups was not significant for 50% or more reduction in tender joint count.

Interpretation: Across the two pivotal phase 3 trials, anifrolumab treatment improved SLE disease activity across multiple organ domains.

Funding: AstraZeneca.