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.