Article Text
Abstract
Objectives In a post-hoc analysis, we aimed to validate the Lupus Low Disease Activity State (LLDAS) definition as an endpoint in an systemic lupus erythematosus (SLE) Phase IIb randomised controlled trial (RCT) (MUSE [NCT01438489]) and then utilize LLDAS to discriminate between anifrolumab and placebo.
Methods Patients received intravenous placebo (n=102) or anifrolumab (300 mg, n=99; 1,000 mg, n=104) Q4W plus standard of care for 48 weeks. LLDAS attainment (SLE Disease Activity Index 2000 ≤4 without major organ activity, no new disease activity, Physician’s Global Assessment ≤1, prednisolone ≤7.5 mg/d and standard immunosuppressant dosage tolerance) was assessed. Associations with endpoints and LLDAS attainment differences between treatments were explored.
Results LLDAS attainment at Week 52 was associated with SLE Responder Index 4 (SRI[4]) and British Isles Lupus Assessment Group–based Composite Lupus Assessment (BICLA) (74/85[87%] and 62/84[74%] were also SRI[4] and BICLA responders, respectively; both nominal p<0.001). Only 74/159 (47%) of SRI(4) and 62/121 (51%) of BICLA responders reached LLDAS.
Anifrolumab-treated patients achieved earlier LLDAS, and more spent at least half their observed time in LLDAS (OR vs. placebo; 300 mg: 3.04, 95% CI 1.34 to 6.92, nominal p=0.008; 1,000 mg: 2.17, 95% CI 0.93 to 5.03, nominal p=0.072) vs placebo-treated patients. At Week 52, 17/102 (17%), 39/99 (39%) and 29/104 (28%) of patients on placebo, anifrolumab 300 and 1,000 mg, respectively, attained LLDAS (OR vs. placebo; 300 mg: 3.41, 95% CI 1.73 to 6.76, p<0.001; 1,000 mg: 2.03, 95% CI 1.01 to 4.07, nominal p=0.046).
Conclusions LLDAS attainment represents a clinically meaningful SLE outcome measure, and anifrolumab is associated with more patients who met LLDAS criteria versus placebo. These data support LLDAS as an SLE RCT endpoint.
Trial registration number NCT1438489; Post-results.
- anifrolumab
- systemic lupus erythematosus
- low disease activity state
- treat-to-target
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Footnotes
Handling editor Josef S Smolen
Contributors EFM: proposed the study design and wrote the manuscript. TT and AB: co-proposed the study design, undertook the statistical analysis and contributed to the manuscript. GI and RT: co-proposed the study design and oversaw the analysis and writing.
Funding AstraZeneca funded the MUSE study.
Competing interests EFM received research support, consultancy or honoraria from AstraZeneca, Bristol Myers Squibb, Glaxo Smith Kline, Janssen and UCB (Union Chimique Belge). TT, AB and RT are employees of AstraZeneca. GI was an employee of Medimmune during the conduct of this analysis; he is currently an employee of Regenxbio.
Ethics approval Independent Ethics Committee or independent Institutional Review Board approvals were obtained from all 101 clinical sites and all patients provided written informed consent in accordance with local requirements.
Provenance and peer review Not commissioned; externally peer reviewed.