Efficacy and safety of ocrelizumab in active proliferative lupus nephritis: results from a randomized, double-blind, phase III study.

OBJECTIVE: To investigate the efficacy and safety of ocrelizumab in patients with class III/IV lupus nephritis (LN).

METHODS: Patients were randomized 1:1:1 to receive placebo, 400 mg ocrelizumab, or 1,000 mg ocrelizumab given as an intravenous infusion on days 1 and 15, followed by a single infusion at week 16 and every 16 weeks thereafter, accompanied by background glucocorticoids plus either mycophenolate mofetil (MMF) or the Euro-Lupus Nephritis Trial (ELNT) regimen (cyclophosphamide followed by azathioprine). The study was terminated early due to an imbalance in serious infections in ocrelizumab-treated patients versus placebo-treated patients. We report week 48 efficacy data for patients receiving ≥32 weeks of treatment (n = 223) and safety results for all treated patients (n = 378).

RESULTS: The overall renal response rate was 54.7%, 66.7%, 67.1%, and 66.9% in the placebo-treated, 400 mg ocrelizumab-treated, 1,000 mg ocrelizumab-treated, and combined ocrelizumab-treated groups, respectively. The associated treatment difference versus placebo for the combined ocrelizumab-treated groups was 12.7% (95% confidence interval [95% CI] -0.8, 26.1) (P = 0.065), with similar differences observed for both ocrelizumab-treated groups. Ocrelizumab versus placebo treatment differences were apparent in patients receiving the background ELNT regimen, but not in those receiving background MMF. A numerically greater proportion of ocrelizumab-treated patients had a ≥50% reduction in the urinary protein:urinary creatinine ratio at 48 weeks compared with placebo-treated patients (placebo-treated patients, 58.7%; 400 mg ocrelizumab-treated patients, 70.7%; 1,000 mg ocrelizumab-treated patients, 68.5%). Serious adverse events occurred in 27.2% of placebo-treated patients, 35.7% of 400 mg ocrelizumab-treated patients, and 22.0% of 1,000 mg ocrelizumab-treated patients. Corresponding serious infection rates (events/100 patient-years) were 18.7 (95% CI 12.2, 28.7), 28.8 (95% CI 20.6, 40.3), and 25.1 (95% CI 17.4, 36.1), respectively. The imbalance in serious infections with ocrelizumab occurred with background MMF but not with the background ELNT regimen.

CONCLUSION: In patients with active LN, overall renal response rates with ocrelizumab were numerically but not statistically significantly superior to those with placebo. Ocrelizumab treatment was associated with a higher rate of serious infections in the subgroup receiving background MMF.