Background and aims LLDAS attainment is associated with reduced organ damage accrual. However, utility of LLDAS as an endpoint has not been evaluated in RCTs. We evaluated LLDAS in a post-hoc analysis of the MUSE trial¹ with patients with moderate to severe SLE.

Methods LLDAS requires SLEDAI–2K<4 without major organ activity, no new disease activity, PGA (0–3)<1, prednisolone <7.5 mg/day, and standard immunosuppressant dosage tolerance. LLDAS attainability, association with trial endpoints, and discrimination between anifrolumab- and placebo-treated patients were explored using descriptive statistics, logistic regression, and Grey’s test.

Results Patients received intravenous placebo, anifrolumab 300 mg, or 1000 mg in addition to standard of care, every 4 weeks for 48 weeks. LLDAS criteria were met at least once by 35%, 52%, and 46% of patients, respectively (Table 1). At Week 52, LLDAS was associated with key trial outcomes. However, LLDAS was more stringent (Table 2). Treatment with anifrolumab 300 mg and 1000 mg increased LLDAS attainment vs. placebo from Week 12 and Week 28, respectively (OR 300 mg: 1.7–3.6; 1000 mg: 1.7–2.5). LLDAS was achieved more frequently at Week 52 (Table 1), and was attained earlier (300 mg: χ²=6.39, p=0.012; 1000 mg: χ²=2.44, p=0.119) (Figure 1) for anifrolumab vs. placebo.

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Abstract 7 Table 1

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Abstract 7 Table 2

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Abstract 7 Table 3

Conclusions LLDAS correlated with clinically relevant treatment responses, discriminating responders from non-responders. Anifrolumab 300 mg treatment was associated with up to 3.6-fold OR increases of LLDAS attainment. LLDAS should be considered as an endpoint in SLE RCTs.

Reference

1. Furie R, et al. Arthritis Rheumtol.2016: in press. Abstract previously submitted to ACR 2016