{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T05:39:30Z","timestamp":1793943570292,"version":"4.8.0"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["JASN"],"published-print":{"date-parts":[[2022,6]]},"abstract":"<jats:sec>\n                    <jats:title>Significance Statement<\/jats:title>\n                    <jats:p>Children with frequently relapsing, steroid-dependent nephrotic syndrome (FRSDNS) often require multiple courses of rituximab. However, long-term effects from repeated treatments remain unknown. In this international, multicenter study of 346 children receiving 1149 courses of rituximab, the risk of relapse decreased and relapse-free survival significantly improved with repeated treatments. Important side effects, including hypogammaglobulinemia, neutropenia, and infections, were mostly mild, but significant adverse events could occur. The incidence of side effects did not increase with more treatment courses nor a higher cumulative dose of rituximab. These findings suggest that repeating rituximab therapy is an effective and reasonably safe approach for most children with FRSDNS.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Long-term outcomes after multiple courses of rituximab among children with frequently relapsing, steroid-dependent nephrotic syndrome (FRSDNS) are unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>A retrospective cohort study at 16 pediatric nephrology centers from ten countries in Asia, Europe, and North America included children with FRSDNS who received two or more courses of rituximab. Primary outcomes were relapse-free survival and adverse events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 346 children (age, 9.8 years; IQR, 6.6\u201313.5 years; 73% boys) received 1149 courses of rituximab. A total of 145, 83, 50, 28, 22, and 18 children received two, three, four, five, six, and seven or more courses, respectively. Median (IQR) follow-up was 5.9 (4.3\u20137.7) years. Relapse-free survival differed by treatment courses (clustered log-rank test\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001). Compared with the first course (10.0 months; 95% CI, 9.0 to 10.7 months), relapse-free period and relapse risk progressively improved after subsequent courses (12.0\u201316.0 months; HR\n                      <jats:sub>adj<\/jats:sub>\n                      , 0.03\u20130.13; 95% CI, 0.01 to 0.18;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt;0.001). The duration of B-cell depletion remained similar with repeated treatments (6.1 months; 95% CI, 6.0 to 6.3 months). Adverse events were mostly mild; the most common adverse events were hypogammaglobulinemia (50.9%), infection (4.5%), and neutropenia (3.7%). Side effects did not increase with more treatment courses nor a higher cumulative dose. Only 78 of the 353 episodes of hypogammaglobulinemia were clinically significant. Younger age at presentation (2.8 versus 3.3 years;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.05), age at first rituximab treatment (8.0 versus 10.0 years;\n                      <jats:italic toggle=\"yes\">P=<\/jats:italic>\n                      0.01), and history of steroid resistance (28% versus 18%;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.01) were associated with significant hypogammaglobulinemia. All 53 infective episodes resolved, except for one patient with hepatitis B infection and another with EBV infection. There were 42 episodes of neutropenia, associated with history of steroid resistance (30% versus 20%;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      =0.04). Upon last follow-up, 332 children (96%) had normal kidney function.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Children receiving repeated courses of rituximab for FRSDNS experience an improving clinical response. Side effects appear acceptable, but significant complications can occur. These findings support repeated rituximab use in FRSDNS.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1681\/asn.2021111472","type":"journal-article","created":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T14:35:16Z","timestamp":1648650916000},"page":"1193-1207","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":105,"title":["Long-Term Efficacy and Safety of Repeated Rituximab to Maintain Remission in Idiopathic Childhood Nephrotic Syndrome: An International Study"],"prefix":"10.1681","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1463-6005","authenticated-orcid":false,"given":"Eugene Yu-hin","family":"Chan","sequence":"first","affiliation":[{"name":"Paediatric Nephrology Centre, Hong Kong Children\u2019s Hospital, Hong Kong SAR"},{"name":"Department of Paediatrics and Adolescent Medicine, University of Hong Kong, Hong Kong SAR"},{"name":"Department of Paediatric Nephrology, Great Ormond Street Hospital for Children, National Health Service Trust, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5768-2100","authenticated-orcid":false,"given":"Ellen L.M.","family":"Yu","sequence":"additional","affiliation":[{"name":"Clinical Research Center, Princess Margaret Hospital, Hong Kong SAR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6121-5326","authenticated-orcid":false,"given":"Andrea","family":"Angeletti","sequence":"additional","affiliation":[{"name":"Nephrology, Dialysis and Transplantation, IRCCS Istituto Giannina Gaslini, Genoa, Italy"},{"name":"Laboratory of Molecular Nephrology, IRCCS Istituto Giannina Gaslini, Genova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zainab","family":"Arslan","sequence":"additional","affiliation":[{"name":"Department of Paediatric Nephrology, Great Ormond Street Hospital for Children, National Health Service Trust, London, United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biswanath","family":"Basu","sequence":"additional","affiliation":[{"name":"Division of Pediatric Nephrology, Nilratan Sircar Medical College and Hospital, Kolkata, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivia","family":"Boyer","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology, Reference Center for Nephrotic Syndrome in Children and Adults, Necker-Enfants Malades Hospital, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), Institut Imagine, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) U1163, Universit\u00e9 Paris Cit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5841-1417","authenticated-orcid":false,"given":"Chang-Yien","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore"},{"name":"Khoo Teck Puat \u2013 National University Children\u2019s Medical Institute, National University Health System, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Colucci","sequence":"additional","affiliation":[{"name":"Renal Diseases Research Unit, Genetics and Rare Diseases Research Division, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3883-1398","authenticated-orcid":false,"given":"Guillaume","family":"Dorval","sequence":"additional","affiliation":[{"name":"Pediatric Nephrology, Reference Center for Nephrotic Syndrome in Children and Adults, Necker-Enfants Malades Hospital, Assistance Publique-H\u00f4pitaux de Paris (AP-HP), Institut Imagine, Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale (INSERM) U1163, Universit\u00e9 Paris Cit\u00e9, Paris, 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of Nephrology, Department of Pediatrics, University of Michigan, CS Mott Children\u2019s Hospital, Ann Arbor, Michigan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7151-459X","authenticated-orcid":false,"given":"Riku","family":"Hamada","sequence":"additional","affiliation":[{"name":"Department of Nephrology and Rheumatology, Tokyo Metropolitan Children\u2019s Medical Center, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julien","family":"Hogan","sequence":"additional","affiliation":[{"name":"Department of Pediatric Nephrology, Robert-Debr\u00e9 Hospital, Reference Center for Nephrotic Syndrome in Children and Adults, Centre de R\u00e9f\u00e9rence Syndrome N\u00e9phrotique de l\u2019Enfant et de l\u2019Adulte (CMR SNI), AP-HP, Universit\u00e9 Paris Cit\u00e9, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenji","family":"Ishikura","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kitasato University School of Medicine, Tokyo, Japan"},{"name":"Department of Pediatrics, Kitasato University Hospital, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koichi","family":"Kamei","sequence":"additional","affiliation":[{"name":"Division of Nephrology and Rheumatology, National Center for Child Health and Development, Tokyo, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus J.","family":"Kemper","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Asklepios Medical School, Hamburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison Lap-tak","family":"Ma","sequence":"additional","affiliation":[{"name":"Paediatric Nephrology Centre, Hong Kong Children\u2019s Hospital, Hong Kong 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