Rife Eileen, Reiff Daniel, Bridges John, Cron Randall Q, Smitherman Emily, Stoll Matthew L, Timmerman Livie, Weiser Peter, Mannion Melissa L
University of Alabama at Birmingham.
Boys Town National Research Hospital, Omaha, Nebraska.
ACR Open Rheumatol. 2025 Sep;7(9):e70095. doi: 10.1002/acr2.70095.
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.
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.
Eighty-nine 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-equivalent daily dose significantly decreased by the end of the follow-up period (P < 0.0001), and 54 patients (62%) were able to discontinue GCs. Patients with systemic lupus erythematosus demonstrated improvements across all serologic disease activity markers (P < 0.0001). Six patients (6.7%) experienced flare of disease, 11 patients (12%) experienced infusion reactions, and 26 patients (31%) experienced incident hypogammaglobinemia.
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.
当前的实践指南推荐使用利妥昔单抗（RTX）或环磷酰胺（CYC）来治疗系统性血管炎或结缔组织病的严重表现。很少有研究评估RTX与CYC联合治疗的安全性和疗效结果。我们开展这项研究以评估风湿性疾病儿科患者接受RTX/CYC联合治疗前12个月的结果。
纳入2020年1月至2023年2月在单一中心接受RTX/CYC联合治疗风湿性疾病的患者。感兴趣的主要结局是联合治疗12个月内的死亡和需要住院治疗的感染。次要结局包括血清学狼疮疾病活动标志物和糖皮质激素（GC）剂量的变化、疾病活动度的复发、输液反应和新发低丙种球蛋白血症。
89名儿科患者接受了RTX/CYC联合治疗风湿性疾病。未报告死亡病例；8名患者（8.9%）因感染住院。随访期末，泼尼松等效日剂量显著降低（P<0.0001），54名患者（62%）能够停用GC。系统性红斑狼疮患者的所有血清学疾病活动标志物均有改善（P<0.0001）。6名患者（6.7%）出现疾病复发，11名患者（12%）出现输液反应，26名患者（31%）出现新发低丙种球蛋白血症。
RTX与CYC联合治疗可安全用于风湿性疾病儿童。严重不良事件和疾病复发的风险并不常见，可有效治疗并减轻GC负担。需要进行前瞻性对照试验，将联合治疗与标准治疗进行比较。
