A phase III randomized controlled trial found that adding obinutuzumab to standard therapy may improve complete renal response rates in patients with active lupus nephritis compared with standard therapy alone, according to findings.
In the REGENCY trial, published in The New England Journal of Medicine, researchers enrolled 271 patients across 15 countries between July 2020 and March 2023. They demonstrated that 46.4% of patients receiving obinutuzumab achieved a complete renal response at 76 weeks vs 33.1% in the placebo group (adjusted difference = 13.4 percentage points, 95% confidence interval [CI] = 2.0–24.8, P = .02).
"Given the importance of B cells in the pathogenesis of lupus nephritis, B-cell depletion is considered to be a scientifically sound therapeutic approach," the study authors wrote.
The patients were randomly assigned to receive one of two obinutuzumab dose schedules (1,000 mg on day 1 and at weeks 2, 24, 26, and 52 with or without an additional dose at week 50) or placebo, along with standard mycophenolate mofetil therapy and oral prednisone. The target prednisone dose was 7.5 mg daily by week 12 and 5 mg daily by week 24.
Secondary endpoints also favored obinutuzumab, with 42.7% achieving complete renal response with prednisone ≤ 7.5 mg daily vs 30.9% in the placebo group (P = .04). Additionally, 55.5% of those in the obinutuzumab group achieved urinary protein-to-creatinine ratios < 0.8 compared with 41.9% in the placebo group (P = .02).
However, serious adverse events occurred more frequently with obinutuzumab (32.4%) vs placebo (18.2%), primarily infections, including those from the COVID-19 virus. When COVID-19 events were excluded, the incidence of serious infections decreased from 16.9% to 11.0% in the obinutuzumab group, with no change (7.6%) in the placebo group.
"The percentage of patients with adverse events was similar in the obinutuzumab group and the placebo group," the study authors noted. "[T]hese risks, and the safety profile of obinutuzumab more broadly, must be considered when deciding whether to initiate treatment," they added.
Four deaths occurred during the 76-week evaluation period: three in the obinutuzumab group (two from COVID-19–related pneumonia and one from nephrotic syndrome) and one in the placebo group (from COVID-19 infections).
The study population was diverse, including substantial representation of groups with historically high lupus nephritis prevalence and complication risks. According to patient-reported race or ethnic group data, Black, Asian, and Hispanic or Latinx patients composed 14.8% (n = 40), 5.9% (n = 16), and 57.6% (n = 156) of the trial population, respectively.
Subgroup analyses showed generally consistent benefits across various baseline characteristics, though differences were observed between male and female patients "because of a high percentage of [male patients] in the placebo group who had a complete renal response (67% in a relatively small subgroup of 21 patients)," the study authors emphasized.
The researchers concluded that obinutuzumab demonstrated superior efficacy compared to standard therapy alone, while noting the need to carefully weigh its benefits against increased infection risks, particularly in the context of COVID-19 infections. Longer-term follow-up data, including estimated glomerular filtration rate outcomes at week 104, are still pending.
Full disclosures can be found in the study.
