Clinical meaningfulness of a British Isles Lupus Assessment Group-based Composite Lupus Assessment response in terms of patient-reported outcomes in moderate to severe systemic lupus erythematosus: a post-hoc analysis of the phase 3 TULIP-1 and TULIP-2 trials of anifrolumab

Vibeke Strand; Sean O'Quinn; Richard A Furie; Eric F Morand; Kenneth C Kalunian; Erik G Schwetje; Gabriel Abreu; Raj Tummala

doi:10.1016/S2665-9913(21)00387-8

Clinical meaningfulness of a British Isles Lupus Assessment Group-based Composite Lupus Assessment response in terms of patient-reported outcomes in moderate to severe systemic lupus erythematosus: a post-hoc analysis of the phase 3 TULIP-1 and TULIP-2 trials of anifrolumab

Lancet Rheumatol. 2022 Mar;4(3):e198-e207. doi: 10.1016/S2665-9913(21)00387-8. Epub 2022 Feb 24.

Authors

Vibeke Strand¹, Sean O'Quinn², Richard A Furie³, Eric F Morand⁴, Kenneth C Kalunian⁵, Erik G Schwetje⁶, Gabriel Abreu⁷, Raj Tummala⁸

Affiliations

¹ Division of Immunology and Rheumatology, Stanford University, Palo Alto, CA, USA.
² BioPharmaceuticals Medical, AstraZeneca, Gaithersburg, MD, USA.
³ Division of Rheumatology, Zucker School of Medicine at Hofstra-Northwell, Great Neck, NY, USA.
⁴ Centre for Inflammatory Disease, Monash University, Melbourne, VIC, Australia.
⁵ Division of Rheumatology, Allergy, and Immunology, University of California, San Diego, La Jolla, CA, USA.
⁶ BioPharmaceuticals Research and Development, AstraZeneca, Gaithersburg, MD, USA.
⁷ BioPharmaceuticals Research and Development, AstraZeneca, Gothenburg, Sweden.
⁸ BioPharmaceuticals Research and Development, AstraZeneca, Gaithersburg, MD, USA. Electronic address: raj.tummala@astrazeneca.com.

PMID: 38288936
DOI: 10.1016/S2665-9913(21)00387-8

Abstract

Background: The British Isles Lupus Assessment Group-based Composite Lupus Assessment (BICLA) is a validated global measure of treatment response in systemic lupus erythematosus (SLE) clinical trials but does not include patient-reported outcomes. To evaluate the clinical meaningfulness of a BICLA response from the patient perspective, we aimed to analyse patient-reported outcomes by BICLA responses with anifrolumab or placebo in patients with moderate to severe SLE.

Methods: We did a post-hoc analysis of pooled data from the phase 3 TULIP-1 (NCT02446912) and TULIP-2 (NCT02446899) trials of anifrolumab, which assessed health-related quality of life using the Short Form 36 Health Survey (SF-36; version 2) and Lupus Quality of Life, fatigue using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F), pain using the Numerical Rating Scale, and disease activity using Patient Global Assessment. Changes from baseline and proportions of patients reporting improvements in patient-reported outcomes greater than or equal to the minimum clinically important differences and scores greater than or equal to the normative values were compared in BICLA responders and non-responders and by treatment group (intravenous anifrolumab 300 mg or placebo).

Findings: 726 patients were included in the TULIP trials, of whom 366 received placebo (184 patients in TULIP-1 and 182 in TULIP-2) and 360 received anifrolumab 300 mg (180 patients in each trial). The mean patient age was 41·8 years (SD 11·9). 674 (93%) patients were female, 52 (7%) were male, and 479 (66%) were White; 283 (39%) were BICLA responders and 443 (61%) were BICLA non-responders. Compared with non-responders, BICLA responders reported greater mean improvements from baseline at week 52 in Patient Global Assessment, SF-36, Lupus Quality of Life, FACIT-F, and pain Numerical Rating Scale scores (all nominal p<0·0053). Compared with non-responders, a greater proportion of BICLA responders reported improvements greater than or equal to the minimum clinically important difference across all SF-36 domains; eg, Physical Component Summary (165 [60%] of 277 for responders vs 63 [15%] of 416 for non-responders), Mental Component Summary (140 [51%] of 276 vs 59 [15%] of 416), and role physical (184 [70%] of 264 vs 76 [19%] of 398); Lupus Quality of Life domains; eg, physical health (151 [58%] of 262 vs 60 [15%] of 396), and intimate relationships (77 [41%] of 187 vs 33 [11%] of 286), and FACIT-F (155 [56%] of 276 vs 66 [15%] of 439). Similarly, a greater proportion of BICLA responders had scores equal to or greater than the normative values across all SF-36 domains and FACIT-F compared with BICLA non-responders at week 52. Patients who received anifrolumab reported greater numerical improvements in Patient Global Assessment, SF-36, Lupus Quality of Life, FACIT-F, and pain Numerical Rating Scale scores than those who received placebo.

Interpretation: BICLA responders reported significant and clinically meaningful improvements in Patient Global Assessment, health-related quality of life, fatigue, and pain compared with BICLA non-responders. More patients with moderate to severe SLE who received anifrolumab were BICLA responders and had improved health-related quality of life, fatigue, and pain than those who received placebo.

Funding: AstraZeneca.