Journal
ANNALS OF THE RHEUMATIC DISEASES
Volume 81, Issue 4, Pages 496-506Publisher
BMJ PUBLISHING GROUP
DOI: 10.1136/annrheumdis-2021-221478
Keywords
autoimmune diseases; biological therapy; immune system diseases; lupus erythematosus; systemic; lupus nephritis
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Funding
- AstraZeneca
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This study evaluated the efficacy and safety of anifrolumab, a type I interferon receptor antibody, in patients with active lupus nephritis. The results showed that anifrolumab IR had numerical improvements over placebo in several endpoints, including complete renal response. However, the primary endpoint of improvement in 24-hour urine protein-creatinine ratio was not met.
Objective To assess the efficacy and safety of the type I interferon receptor antibody, anifrolumab, in patients with active, biopsy-proven, Class III/IV lupus nephritis. Methods This phase II double-blinded study randomised 147 patients (1:1:1) to receive monthly intravenous anifrolumab basic regimen (BR, 300 mg), intensified regimen (IR, 900 mg x3, 300 mg thereafter) or placebo, alongside standard therapy (oral glucocorticoids, mycophenolate mofetil). The primary endpoint was change in baseline 24-hour urine protein-creatinine ratio (UPCR) at week (W) 52 for combined anifrolumab versus placebo groups. The secondary endpoint was complete renal response (CRR) at W52. Exploratory endpoints included more stringent CRR definitions and sustained glucocorticoid reductions (<= 7.5 mg/day, W24-52). Safety was analysed descriptively. Results Patients received anifrolumab BR (n=45), IR (n=51), or placebo (n=49). At W52, 24-hour UPCR improved by 69% and 70% for combined anifrolumab and placebo groups, respectively (geometric mean ratio=1.03; 95% CI 0.62 to 1.71; p=0.905). Serum concentrations were higher with anifrolumab IR versus anifrolumab BR, which provided suboptimal exposure. Numerically more patients treated with anifrolumab IR vs placebo attained CRR (45.5% vs 31.1%), CRR with UPCR <= 0.5 mg/mg (40.9% vs 26.7%), CRR with inactive urinary sediment (40.9% vs 13.3%) and sustained glucocorticoid reductions (55.6% vs 33.3%). Incidence of herpes zoster was higher with combined anifrolumab vs placebo (16.7% vs 8.2%). Incidence of serious adverse events was similar across groups. Conclusion Although the primary endpoint was not met, anifrolumab IR was associated with numerical improvements over placebo across endpoints, including CRR, in patients with active lupus nephritis.
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