Intensified anifrolumab regimen linked with numerical improvements in lupus nephritis
Despite not reaching the primary endpoint in this phase 2 randomized trial of type I interferon inhibitor anifrolumab in patients with active lupus nephritis, treatment with an intensified regimen (IR, 900 mg ×3, 300 mg thereafter) was associated with numerical improvements across endpoints when compared to placebo.
Patients (n = 147) were randomized to receive monthly intravenous anifrolumab basic regimen (BR, 300 mg), IR, 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 52 for combined anifrolumab versus placebo groups.
Secondary and exploratory endpoints were complete renal response (CRR) at week 52 and more stringent CRR definitions and sustained glucocorticoid reductions (≤7.5 mg/day, weeks 24-52), respectively.
Overall, 45 patients received anifrolumab BR, 51 patients received IR, and 49 patients received placebo. At week 52, 24-hour UPCR improved by 69% in patients treated with combined anifrolumab and 70% in patients receiving placebo. Serum concentrations were higher with anifrolumab IR versus anifrolumab BR, which the authors stated provided suboptimal exposure.
CRR, CRR with UPCR ≤0.5 mg/mg, and CRR with inactive urinary sediment was attained in 45.5%, 40.9%, and 40.9% of patients treated with anifrolumab IR, respectively, compared with 31.1%, 26.7%, and 13.3% of patients treated with placebo, respectively.
Overall, 55.6% of patients treated with anifrolumab IR experienced sustained glucocorticoid reductions compared with 33.3% of patients treated with placebo.
Incidence of serious adverse events was similar across groups; however, the incidence of herpes zoster was higher in patients treated with combined anifrolumab compared with placebo (16.7% vs 8.2%).
Jayne D, Rovin B, Mysler EF, et al. Phase II randomised trial of type I interferon inhibitor anifrolumab in patients with active lupus nephritis. Ann Rheum Dis. 2022;annrheumdis-2021-221478. doi: 10.1136/annrheumdis-2021-221478. Epub ahead of print. PMID: 35144924.