Journal article
Concordance and discordance in SLE clinical trial outcome measures: analysis of three anifrolumab phase 2/3 trials
Annals of the rheumatic diseases, v 81(7), pp 962-969
01 Jul 2022
PMID: 35580976
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Objectives In the anifrolumab systemic lupus erythematosus (SLE) trial programme, there was one trial (TULIP-1) in which BILAG-based Composite Lupus Assessment (BICLA) responses favoured anifrolumab over placebo, but the SLE Responder Index (SRI(4)) treatment difference was not significant. We investigated the degree of concordance between BICLA and SRI(4) across anifrolumab trials in order to better understand drivers of discrepant SLE trial results.
Methods TULIP-1, TULIP-2 (both phase 3) and MUSE (phase 2b) were randomised, 52-week trials of intravenous anifrolumab (300 mg every 4 weeks, 48 weeks; TULIP-1/TULIP-2: n=180; MUSE: n=99) or placebo (TULIP-1: n=184, TULIP-2: n=182; MUSE: n=102). Week 52 BICLA and SRI(4) outcomes were assessed for each patient.
Results Most patients (78%-85%) had concordant BICLA and SRI(4) outcomes (Cohen's Kappa 0.6-0.7, nominal p<0.001). Dual BICLA/SRI(4) response rates favoured anifrolumab over placebo in TULIP-1, TULIP-2 and MUSE (all nominal p <= 0.004). A discordant TULIP-1 BICLA non-responder/SRI(4) responder subgroup was identified (40/364, 11% of TULIP-1 population), comprising more patients receiving placebo (n=28) than anifrolumab (n=12). In this subgroup, placebo-treated patients had lower baseline disease activity, joint counts and glucocorticoid tapering rates, and more placebo-treated patients had arthritis response than anifrolumab-treated patients.
Conclusions Across trials, most patients had concordant BICLA/SRI(4) outcomes and dual BICLA/SRI(4) responses favoured anifrolumab. A BICLA nonresponder/SRI(4) responder subgroup was identified where imbalances of key factors driving the BICLA/SRI(4) discordance (disease activity, glucocorticoid taper) disproportionately favoured the TULIP-1 placebo group. Careful attention to baseline disease activity and monitoring glucocorticoid taper variation will be essential in future SLE trials.
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Details
- Title
- Concordance and discordance in SLE clinical trial outcome measures: analysis of three anifrolumab phase 2/3 trials
- Creators
- Ian N. Bruce - Manchester Academic Health Science CentreRichard A. Furie - Donald & Barbara Zucker School of Medicine at Hofstra/NorthwellEric F. Morand - Monash UniversitySusan Manzi - Allegheny Health NetworkYoshiya Tanaka - University of Occupational and Environmental Health JapanKenneth C. Kalunian - University of California, San DiegoJoan T. Merrill - Oklahoma Medical Research FoundationPatricia Puzio - AstraZenecaEmmanuelle Maho - AstraZenecaChristi Kleoudis - AstraZenecaMarius Albulescu - AstraZenecaMicki Hultquist - AstraZenecaRaj Tummala - AstraZeneca
- Publication Details
- Annals of the rheumatic diseases, v 81(7), pp 962-969
- Publisher
- Bmj Publishing Group
- Number of pages
- 8
- Grant note
- AstraZeneca NIHR Manchester Biomedical Research Centre; National Institutes of Health Research (NIHR)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- General Internal Medicine
- Web of Science ID
- WOS:000797586800001
- Scopus ID
- 2-s2.0-85132311657
- Other Identifier
- 991021934005104721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Rheumatology