TOPLINE:

Rituximab vs placebo significantly improved the 49-week relapse-free rate in adults with frequently relapsing or steroid-dependent adult-onset nephrotic syndrome. Adverse events were more common in the rituximab group than in the placebo group.

METHODOLOGY:

• Corticosteroids are often used to manage nephrotic syndrome, but their long-term use is tied to adverse effects such as osteoporosis and infections. Rituximab, an anti-CD20 monoclonal antibody, is approved for childhood-onset nephrotic syndrome in Japan but not for adult-onset cases.
• Researchers conducted a randomized placebo-controlled trial at 13 centers in Japan to assess the effects of rituximab in patients with adult-onset frequently relapsing or steroid-dependent nephrotic syndrome.
• They included 66 adults with frequently relapsing nephrotic syndrome (defined as relapsing more than twice in 6 months) or steroid-dependent nephrotic syndrome and with urine protein levels < 0.3 g/gCr at two or more tests after corticosteroid treatment initiation.
• Participants were randomly assigned to receive either 375 mg/m² rituximab (n = 32; mean age, 49.1 years; 53.1% female) or a placebo (n = 34; mean age, 46.8 years; 58.8% female) at weeks 1, 2, and 25, with a follow-up period of 49 weeks. Corticosteroid doses were maintained for 4 weeks after the first administration of rituximab, then tapered every 4 weeks for patients taking corticosteroids at enrollment; doses of other immunosuppressants were adjusted after the discontinuation of corticosteroids at the physician’s discretion.
• The primary outcome was the proportion of patients who remained relapse-free at 49 weeks, with relapse defined as a urine protein level ≥ 1 g/gCr on two consecutive measurements. Adverse events were monitored after the first administration of rituximab.

TAKEAWAY:

• The relapse-free rate at 49 weeks was higher in the rituximab group than in the placebo group (87.4% vs 38.0%; P < .001). Dropout rates were 12.5% vs 3.0% in the rituximab group vs the placebo group.
• The risk for relapse was reduced in the rituximab group vs the placebo group (hazard ratio, 0.16; P < .001). The median time to relapse was over 49 weeks vs 30.8 weeks in the rituximab group vs the placebo group.
• At 49 weeks, the proportions of patients who discontinued corticosteroids were 71.9% vs 36.4% in the rituximab group vs the placebo group (P = .006).
• Infusion reactions were the most common adverse effect, occurring in 40.6% vs 2.9% of patients in the rituximab group vs the placebo group; grade 3 treatment-related adverse effects were noted in no patients in the rituximab group (0% vs 2.9%).

IN PRACTICE:

“These findings support the safety and efficacy of rituximab for preventing relapse of FRNS/SDNS [frequently relapsing nephrotic syndrome/steroid-dependent nephrotic syndrome],” the authors of the study wrote.

“By reducing the frequency of relapses, rituximab may help adult patients reduce their reliance on corticosteroids and improve their overall quality of life,” second author Yusuke Sakaguchi said in a press release.

SOURCE:

The study was led by Yoshitaka Isaka, MD, PhD, Department of Nephrology, The University of Osaka Graduate School of Medicine, Suita, Japan. It was published online in JAMA.

LIMITATIONS:

The follow-up period of the study was limited to 6 months post-rituximab administration, and long-term effects were not evaluated. The sample size was small, and there were imbalances between the study groups. The study did not determine if results were due to B-cell depletion or another factor.

DISCLOSURES:

The study was funded by Zenyaku Kogyo Co., Ltd., which also provided rituximab and placebo and managed the research, including pharmacokinetic analysis and manuscript approval for publication. Some authors reported receiving personal fees, lecture honoraria, or grants from various pharmaceutical companies. One author reported conducting collaborative research for Zenyaku Kogyo Co., Ltd. unrelated to the study.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.