{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T22:10:19Z","timestamp":1782252619721,"version":"3.54.5"},"reference-count":30,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2025,9,15]],"date-time":"2025-09-15T00:00:00Z","timestamp":1757894400000},"content-version":"vor","delay-in-days":14,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["T32 AR 069516"],"award-info":[{"award-number":["T32 AR 069516"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000980","name":"Arthritis Foundation","doi-asserted-by":"publisher","award":["344848.01.01.2024365.10"],"award-info":[{"award-number":["344848.01.01.2024365.10"]}],"id":[{"id":"10.13039\/100000980","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000069","name":"National Institute of Arthritis and Musculoskeletal and Skin Diseases","doi-asserted-by":"publisher","award":["K23\u2010AR\u2010081410"],"award-info":[{"award-number":["K23\u2010AR\u2010081410"]}],"id":[{"id":"10.13039\/100000069","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["acrjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ACR Open Rheumatology"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Current practice guidelines recommend the use of either rituximab (RTX) or cyclophosphamide (CYC) for the treatment of severe manifestations of systemic vasculitis or connective tissue disease. Few studies have evaluated safety and efficacy outcomes of combination therapy with RTX and CYC. We undertook this study to evaluate outcomes in the first 12 months of RTX\/CYC combination therapy in pediatric patients with rheumatic disease.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Patients who received combination RTX\/CYC therapy for a rheumatic disease between January 2020 and February 2023 at a single center were included. The primary outcomes of interest were death and infection requiring hospitalization within 12 months of combination therapy. Secondary outcomes included change in serologic lupus disease activity markers and glucocorticoid (GC) dose, flare in disease activity, infusion reactions, and incident hypogammaglobulinemia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Eighty\u2010nine pediatric patients received combination RTX\/CYC therapy for a rheumatic disease. There were no reported deaths; eight patients (8.9%) were hospitalized for infection. The mean prednisone\u2010equivalent daily dose significantly decreased by the end of the follow\u2010up period (<jats:italic>P<\/jats:italic> &lt; 0.0001), and 54 patients (62%) were able to discontinue GCs. Patients with systemic lupus erythematosus demonstrated improvements across all serologic disease activity markers (<jats:italic>P<\/jats:italic> &lt; 0.0001). Six patients (6.7%) experienced flare of disease, 11 patients (12%) experienced infusion reactions, and 26 patients (31%) experienced incident hypogammaglobinemia.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Combination therapy with RTX and CYC can be safely administered to children with rheumatic diseases. Risk of serious adverse events and disease flare is uncommon, allowing for effective treatment with decreased GC burden. Prospective controlled trials comparing combination therapy to standard therapy are needed.<\/jats:p><\/jats:sec>","DOI":"10.1002\/acr2.70095","type":"journal-article","created":{"date-parts":[[2025,9,16]],"date-time":"2025-09-16T05:16:21Z","timestamp":1757999781000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Safety and Effectiveness of Combination Rituximab and Cyclophosphamide Therapy for Treating Pediatric Patients With Severe Manifestations of Rheumatic Disease"],"prefix":"10.1002","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-8529-4830","authenticated-orcid":false,"given":"Eileen","family":"Rife","sequence":"first","affiliation":[{"name":"University of Alabama at Birmingham"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Reiff","sequence":"additional","affiliation":[{"name":"Boys Town National Research Hospital  Omaha 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