Is Obinutuzumab the Answer to Primary Membranous Nephropathy Resistant to Rituximab?

Membranous nephropathy (MN) is the most common cause of nephrotic syndrome in non-diabetic adults worldwide. Historically, patients that needed immunosuppression were treated with cytotoxic drugs or calcineurin inhibitors, which were effective but associated with a significant risk of toxicity long-term. The treatment landscape changed after the seminal work by Remuzzi et al. in 2002 reporting on the successful use of rituximab in 8 patients with MN.[1] Since then, a number of studies have documented the efficacy of rituximab in inducing proteinuria remission in MN,[2] (see supplemental references) with up to 80% of the patients reaching complete (CR) or partial remission (PR) of proteinuria at 24 months.[3] In a recent retrospective study of 159 patients with MN [108 (75.5%) had PLA2R-Ab-associated MN (PLA2R-MN)] 140 of 159 (88.1%) of the patients achieved CR or PR after a median follow-up of 62.6 months.[4] Failure to respond to RTX was observed in only 11.9% of patients, with only 7 of 159 (4.4%) developing ESKD with an estimated renal survival of 97% (95% confidence interval [CI]: 94%-100%) and 95.4% (95% CI: 91.2%-99%) at 5 and 10 years, respectively.