{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:43:23Z","timestamp":1791924203416,"version":"4.3.4"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2022,7,30]],"date-time":"2022-07-30T00:00:00Z","timestamp":1659139200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"name":"Undergraduate Research Grant scheme"},{"DOI":"10.13039\/501100007338","name":"All-India Institute of Medical Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007338","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Department of Biotechnology, Government of India","award":["BT\/PR11030\/MED\/30\/1644\/2016"],"award-info":[{"award-number":["BT\/PR11030\/MED\/30\/1644\/2016"]}]},{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["5\/7\/1090\/2013-RHN"],"award-info":[{"award-number":["5\/7\/1090\/2013-RHN"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,3,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Sequential rituximab (RTX) administration has emerged as an important strategy to sustain remission of disease in patients with difficult-to-treat nephrotic syndrome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We report the efficacy and safety of sequential therapy with two or more courses of intravenous RTX in 250 patients with difficult-to-treat steroid dependence (n\u00a0=\u00a0127) and calcineurin inhibitor (CNI)-dependent or CNI-refractory steroid resistance (n\u00a0=\u00a0123) managed at one center during 2015\u20132021. Subsets of patients were cross-sectionally tested for hypogammaglobulinemia, seroprotection against and hyporesponsiveness to vaccines for hepatitis B and tetanus, BK\/JC viruria and human antichimeric antibodies (HACAs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Sequential RTX therapy, initiated at a median of 10\u00a0years [interquartile range (IQR) 7.3\u201314.4], was administered for 1.8\u00a0courses\/person-year [95% confidence interval (CI) 1.7\u20132.0] over 2.0\u00a0years (95% CI 1.2\u20133.0). Therapy was associated with postponement of relapses by a median of 3\u00a0years in patients with steroid-sensitive disease and 2\u00a0years in those with steroid resistance. Relapses were reduced by a mean of 2.0\u00a0relapses\/person-year (95% CI 1.8\u20132.2), enabling a reduction in prednisolone dose to 0.04\u00a0mg\/kg\/day (95% CI 0.01\u20130.11) and withdrawal of additional immunosuppression in 154 (62%) patients. RTX-associated adverse events, occurring at 0.20\u00a0events\/person-year (95% CI 0.17\u20130.23), were chiefly comprised of infusion reactions (n\u00a0=\u00a0108) and infections (n\u00a0=\u00a046); serious adverse events were observed in 10.8% patients, at 0.03\u00a0events\/person-year (95% CI 0.02\u20130.05). Hypogammaglobulinemia was observed in 35% of 177 patients and was moderate to severe in 8.5% of cases. Rates of seroprotection at baseline and response following vaccination were lower for hepatitis B [1.9% and 29.4% (n\u00a0=\u00a052)] than tetanus [65.5% and 34.5% (n\u00a0=\u00a058)]. BK\/JC viruria, without viremia, was observed in 7.3% of 109 cases. A total of 19 of 107 patients (17.8%) had HACAs, which were associated with B cell nondepletion and serum sickness. Age at therapy of &amp;lt;9\u201310\u00a0years was associated with a risk of early relapse, treatment failure and hypogammaglobulinemia following RTX therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Sequential therapy with RTX effectively reduces relapses in patients with difficult-to-treat steroid- and\/or CNI-dependent or CNI-refractory nephrotic syndrome. Therapy is associated with high rates of hypogammaglobulinemia and infusion reactions.<\/jats:p><\/jats:sec>","DOI":"10.1093\/ndt\/gfac228","type":"journal-article","created":{"date-parts":[[2022,9,8]],"date-time":"2022-09-08T03:39:09Z","timestamp":1662608349000},"page":"939-949","source":"Crossref","is-referenced-by-count":32,"title":["Sequential rituximab therapy sustains remission of nephrotic syndrome but carries high risk of adverse effects"],"prefix":"10.1093","volume":"38","author":[{"given":"Aditi","family":"Sinha","sequence":"first","affiliation":[{"name":"Division of Nephrology and ICMR Center for Advanced Research in Nephrology, Department of Pediatrics, All India Institute of Medical Sciences , New Delhi , India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georgie","family":"Mathew","sequence":"additional","affiliation":[{"name":"Division of Nephrology and ICMR Center for Advanced Research in Nephrology, Department of Pediatrics, All India Institute of 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