{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T10:44:41Z","timestamp":1793357081135,"version":"4.5.0"},"reference-count":30,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2021,4]]},"abstract":"\n Significance Statement<\/jats:title>\n A cyclic regimen of corticosteroid and cyclophosphamide is the first-line therapy for membranous nephropathy. Rituximab is superior to conservative treatment and noninferior to cyclosporine in inducing remission; it also may have a more favorable safety profile compared with cyclic therapy, but a head-to-head comparison of rituximab versus cyclic therapy is lacking. Using a multisite design, the authors designed a pilot randomized trial to obtain estimates of the effects of the two therapies and to assess the recruitment potential of a noninferiority trial. They found rituximab and cyclophosphamide may have comparable effects on disease remission and a similar short-term safety profile. These data suggest that, although rituximab may be a valid alternative to cyclic therapy for patients with membranous nephropathy, a head-to-head pragmatic comparison would require a large, global, noninferiority trial.<\/jats:p>\n <\/jats:sec>\n \n Background<\/jats:title>\n A cyclic corticosteroid-cyclophosphamide regimen is the first-line therapy for membranous nephropathy. Compared with this regimen, rituximab therapy might have a more favorable safety profile, but a head-to-head comparison is lacking.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n We randomly assigned 74 adults with membranous nephropathy and proteinuria >3.5 g\/d to rituximab (1 g) on days 1 and 15, or a 6-month cyclic regimen with corticosteroids alternated with cyclophosphamide every other month. The primary outcome was complete remission of proteinuria at 12 months. Other outcomes included determination of complete or partial remission at 24 months and occurrence of adverse events.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n At 12 months, six of 37 patients (16%) randomized to rituximab and 12 of 37 patients (32%) randomized to the cyclic regimen experienced complete remission (odds ratio [OR], 0.4; 95% CI, 0.13 to 1.23); 23 of 37 (62%) receiving rituximab and 27 of 37 (73%) receiving the cyclic regimen had complete or partial remission (OR, 0.61; 95% CI, 0.23 to 1.63). At 24 months, the probabilities of complete and of complete or partial remission with rituximab were 0.42 (95% CI, 0.26 to 0.62) and 0.83 (95% CI, 0.65 to 0.95), respectively, and 0.43 (95% CI, 0.28 to 0.61) and 0.82 (95% CI, 0.68 to 0.93), respectively, with the cyclic regimen. Serious adverse events occurred in 19% of patients receiving rituximab and in 14% receiving the cyclic regimen.<\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n This pilot trial found no signal of more benefit or less harm associated with rituximab versus a cyclic corticosteroid-cyclophosphamide regimen in the treatment of membranous nephropathy. A head-to-head, pragmatic comparison of the cyclic regimen versus rituximab may require a global noninferiority trial.<\/jats:p>\n <\/jats:sec>\n \n Clinical Trial registry name and registration number:<\/jats:title>\n Rituximab versus Steroids and Cyclophosphamide in the Treatment of Idiopathic Membranous Nephropathy (RI-CYCLO), NCT03018535<\/jats:p>\n <\/jats:sec>","DOI":"10.1681\/asn.2020071091","type":"journal-article","created":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T12:35:15Z","timestamp":1614602115000},"page":"972-982","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":234,"title":["Rituximab or Cyclophosphamide in the Treatment of Membranous Nephropathy: The RI-CYCLO Randomized Trial"],"prefix":"10.1681","volume":"32","clinical-trial-number":[{"clinical-trial-number":"nct03018535","registry":"10.18810\/clinical-trials-gov","type":"results"}],"author":[{"given":"Francesco","family":"Scolari","sequence":"first","affiliation":[{"name":"Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy"},{"name":"Nephrology Unit, Spedali Civili Hospital, ASST Spedali Civili of Brescia, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisa","family":"Delbarba","sequence":"additional","affiliation":[{"name":"Nephrology Unit, Spedali Civili Hospital, ASST Spedali Civili of Brescia, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Domenico","family":"Santoro","sequence":"additional","affiliation":[{"name":"Unit of Nephrology and Dialysis, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Loreto","family":"Gesualdo","sequence":"additional","affiliation":[{"name":"Nephrology Unit, Department of Emergency and Transplant Organs, University Aldo Moro of Bari, Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonello","family":"Pani","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Dialysis, G. Brotzu Hospital, Cagliari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Dallera","sequence":"additional","affiliation":[{"name":"Nephrology Unit, Montichiari Hospital, ASST Spedali Civili of Brescia, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4693-7814","authenticated-orcid":false,"given":"Laila-Yasmin","family":"Mani","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marisa","family":"Santostefano","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Dialysis and Hypertension, Policlinico S.Orsola-Malpighi Hospital, Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandro","family":"Feriozzi","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Belcolle Hospital, Viterbo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Quaglia","sequence":"additional","affiliation":[{"name":"Division of Nephrology, University of Piemonte Orientale, Novara, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuliano","family":"Boscutti","sequence":"additional","affiliation":[{"name":"Division of Nephrology, University Hospital of Udine, Udine, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Ferrantelli","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Cervello Hospital, Palermo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmelita","family":"Marcantoni","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Policlinico di Catania Hospital, Catania, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrizia","family":"Passerini","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Policlinico Hospital, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3319-0248","authenticated-orcid":false,"given":"Riccardo","family":"Magistroni","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Policlinico of Modena Hospital, Modena, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1686-5709","authenticated-orcid":false,"given":"Federico","family":"Alberici","sequence":"additional","affiliation":[{"name":"Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy"},{"name":"Nephrology Unit, Spedali Civili Hospital, ASST Spedali Civili of Brescia, Brescia, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3659-9062","authenticated-orcid":false,"given":"Gian Marco","family":"Ghiggeri","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Dialysis and Transplantation, Scientific Institute for Research and Health Care, IRCCS Istituto Giannina Gaslini, Genoa, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudio","family":"Ponticelli","sequence":"additional","affiliation":[{"name":"Independent Researcher, Past Director of the Division of Nephrology of the Policlinico Hospital, Milano, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Ravani","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of Calgary, Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the RI-CYCLO 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