Personalized phospholipase A2 receptor antibody–driven rituximab treatment strategy in membranous nephropathy

In the Sequential Treatment with Tacrolimus and Rituximab versus Alternating Corticosteroids and Cyclophosphamide in Primary Membranous Nephropathy trial, Fernández-Juárez et al. have shown that a sequential tacrolimus/rituximab protocol is effective yet inferior to the standard cyclophosphamide/corticosteroid combination to treat membranous nephropathy. Adverse events were more frequent in the cyclophosphamide/corticosteroid group. 1 Fernández-Juárez G. Rojas-Rivera J. van de Logt A. et al. STARMEN investigators. The STARMEN trial indicates that alternating treatment with corticosteroids and cyclophosphamide is superior to sequential treatment with tacrolimus and rituximab in primary membranous nephropathy. Kidney Int. 2021; 99: 986-998 Abstract Full Text Full Text PDF PubMed Scopus (85) Google Scholar Previous studies have shown that cyclophosphamide/corticosteroid combination allows earlier and higher immunological remission rate than does rituximab alone 2 Van de Logt A. Dahan K. Rousseau A. et al. Immunological remission in PLA2R-antibody–associated membranous nephropathy: cyclophosphamide versus rituximab. Kidney Int. 2018; 93: 1016-1017 Abstract Full Text Full Text PDF PubMed Scopus (46) Google Scholar and that rituximab is efficient and not inferior to cyclosporine. 3 Fervenza F.C. Appel G.B. Barbour S.J. et al. Rituximab or cyclosporine in the treatment of membranous nephropathy. N Engl J Med. 2019; 381: 36-46 Crossref PubMed Scopus (290) Google Scholar ,4 Dahan K. Debiec H. Plaisier E. et al. GEMRITUX Study GroupRituximab for severe membranous nephropathy: a 6-month trial with extended follow-up. J Am Soc Nephrol. 2017; 28: 348-358 Crossref PubMed Scopus (262) Google Scholar The STARMEN trial indicates that alternating treatment with corticosteroids and cyclophosphamide is superior to sequential treatment with tacrolimus and rituximab in primary membranous nephropathyKidney InternationalVol. 99Issue 4PreviewA cyclical corticosteroid-cyclophosphamide regimen is recommended for patients with primary membranous nephropathy at high risk of progression. We hypothesized that sequential therapy with tacrolimus and rituximab is superior to cyclical alternating treatment with corticosteroids and cyclophosphamide in inducing persistent remission in these patients. This was tested in a randomized, open-label controlled trial of 86 patients with primary membranous nephropathy and persistent nephrotic syndrome after six-months observation and assigned 43 each to receive six-month cyclical treatment with corticosteroid and cyclophosphamide or sequential treatment with tacrolimus (full-dose for six months and tapering for another three months) and rituximab (one gram at month six). Full-Text PDF Open AccessImmunological remission in PLA2R-antibody–associated membranous nephropathy: cyclophosphamide versus rituximabKidney InternationalVol. 93Issue 4PreviewFor the treatment of patients with idiopathic membranous nephropathy, rituximab is considered an alternative to alkylating agents. Still, the nonresponse rate to rituximab is approximately 35%,1,2 and partial remission rate is lower with rituximab compared with cyclophosphamide.3 The discovery of antibodies against PLA2R (aPLA2R) has positioned immunological remission as a major goal in the treatment of idiopathic membranous nephropathy. We questioned whether rituximab is less effective than cyclophosphamide in inducing an immunological remission in patients with idiopathic membranous nephropathy. Full-Text PDF Open ArchiveThe authors replyKidney InternationalVol. 99Issue 4PreviewWe thank Delafosse et al. for their comments and congratulate them for the results obtained in their cohort of patients with membranous nephropathy treated with an anti–phospholipase A2 receptor-driven rituximab protocol.1 We agree that the availability of anti–phospholipase A2 receptor monitoring will allow a more personalized and flexible treatment of membranous nephropathy. Full-Text PDF