Gagne Samuel J, Sivaraman Vidya, Bosman Else S, Klamer Brett, Morishita Kimberly A, Huber Adam, Orjuela Alvaro, Eberhard Barbara, Myrup Charlotte, Gerstbacher Dana, Foell Dirk, Al-Abadi Eslam, McErlane Flora, Cook Kathryn, Wagner-Weiner Linda, Elder Melissa, Moorthy L Nandini, Dancey Paul, Yeung Rae, Khubchandani Raju, Deepak Samundeeswari, Charuvanij Sirirat, Tarvin Stacey, Shenoi Susan, Tanner Tamara, Brown Kelly, Cabral David A
Children's Hospital of Pittsburgh of University of Pittsburgh Medical Center and University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania.
Nationwide Children's Hospital and The Ohio State University, Columbus, Ohio.
Arthritis Care Res (Hoboken). 2025 Apr;77(4):504-512. doi: 10.1002/acr.25455. Epub 2024 Dec 10.
Granulomatosis with polyangiitis (GPA) and microscopic polyangiitis (MPA) are chronic life-threatening vasculitides requiring substantial immunotherapy. Adult trials identified rituximab (RTX) as an alternative to cyclophosphamide (CYC) for remission induction of GPA and MPA. Disease rarity has limited feasibility of similar trials with pediatric patients. We aim to evaluate the relative efficacy and toxicity of CYC and RTX for patients with childhood GPA and MPA through registry-based comparative evaluation.
From A Registry of Childhood Vasculitis, we identified patients with GPA and MPA who received induction with RTX or CYC. Pediatric Vasculitis Activity Score (PVAS) and Pediatric Vasculitis Damage Index (pVDI) score evaluated disease activity and damage. Descriptive statistics summarized patient characteristics. RTX and CYC comparisons used logistic regression for primary outcomes of postinduction remission (PVAS = 0) or low disease activity (PVAS ≤ 2). Hospital admission for adverse events and pVDI scores were compared using logistic regression and ordinal regression, respectively.
Among 104 patients, 43% received RTX, 46% CYC, 11% both. Treatment groups did not significantly differ for diagnosis PVAS and onset age. There was no difference in remission among the groups (63% overall; odds ratio [OR] 1.07, 95% confidence interval [CI] 0.45-2.52). Hospitalizations occurred in 22% of patients receiving RTX versus 10% patients receiving CYC (OR 2.27, 95% CI 0.73-7.05). The median 12-month pVDI score was 1 in both groups (OR 0.98, 95% CI 0.43-2.22).
This is the first study comparing CYC and RTX for induction in pediatric GPA and MPA. No significant differences were shown in rates of remission, severe adverse events, or organ damage. Limitations included lack of standardized treatment regimens, retrospectivity, and lack of longitudinal adverse drug-related event data.
肉芽肿性多血管炎（GPA）和显微镜下多血管炎（MPA）是危及生命的慢性血管炎，需要大量免疫治疗。成人试验确定利妥昔单抗（RTX）可作为环磷酰胺（CYC）的替代药物用于诱导GPA和MPA缓解。疾病罕见性限制了在儿科患者中进行类似试验的可行性。我们旨在通过基于登记处的比较评估来评估CYC和RTX对儿童GPA和MPA患者的相对疗效和毒性。
从儿童血管炎登记处，我们确定了接受RTX或CYC诱导治疗的GPA和MPA患者。儿科血管炎活动评分（PVAS）和儿科血管炎损伤指数（pVDI）评分用于评估疾病活动和损伤情况。描述性统计总结了患者特征。RTX和CYC的比较使用逻辑回归分析诱导后缓解（PVAS = 0）或低疾病活动（PVAS≤2）的主要结局。分别使用逻辑回归和有序回归比较不良事件导致的住院情况和pVDI评分。
在104例患者中，43%接受RTX治疗，46%接受CYC治疗，11%两者都接受。治疗组在诊断PVAS和发病年龄方面无显著差异。各组间缓解情况无差异（总体缓解率63%；优势比[OR]1.07，95%置信区间[CI]0.45 - 2.52）。接受RTX治疗的患者中有22%发生住院，而接受CYC治疗的患者中有10%发生住院（OR 2.27，95% CI 0.73 - 7.05）。两组的12个月pVDI评分中位数均为1（OR 0.98，95% CI 0.43 - 2.22）。
这是第一项比较CYC和RTX用于儿童GPA和MPA诱导治疗的研究。在缓解率、严重不良事件或器官损伤方面未显示出显著差异。局限性包括缺乏标准化治疗方案、回顾性研究以及缺乏纵向药物相关不良事件数据。
