Department of Paediatric Immunology, Rheumatology and Infectious Diseases, Amsterdam UMC location University of Amsterdam; and Department of Paediatrics, Zaans Medical Center, Zaandam, The Netherlands.
Department of Paediatric Immunology, Rheumatology and Infectious Diseases, Amsterdam UMC location University of Amsterdam, The Netherlands.
Clin Exp Rheumatol. 2023 Nov;41(11):2323-2330. doi: 10.55563/clinexprheumatol/yqjz1s. Epub 2023 Jul 13.
Rituximab (RTX), used for treatment in paediatric immune-mediated diseases, can lead to hypogammaglobulinaemia and thus to an increased risk of infection, but data on these adverse effects in children are scarce. We aimed to describe the pharmacodynamics of RTX by time to B cell repopulation in paediatric immune-mediated diseases and to assess whether low post-RTX immunoglobulin levels were associated with frequency and severity of infections.
Data of children with autoimmune diseases (AID), immune dysregulation (ID), haematological diseases (HD) and renal diseases (RD), including immunoglobulin levels pre-/post-RTX and occurrence of infections, who had received RTX at our centre were retrospectively collected. B cell depletion was defined as B cells <10 cells/μl.
Post-RTX B cell depletion was achieved in 45/49 patients. In 30/45 patients with B cell repopulation, median time to repopulation was 166 days (IQR 140-224): AID group (n=9) (183 days (IQR 156-239), ID group (n=6) 170 days (IQR 128-184), HD group (n=7) 139 days (IQR 127-294), RD group (n=7) 160 days (IQR 121-367). Severe infections leading to hospitalisation occurred in 7/52 (13.5%) patients: ID (n=3), HD (n=1), RD (n=3). After RTX treatment, 13/52 patients (25%) had low IgG levels for their age at least once, 11/13 had an infection during low IgG but only 2/13 had a severe infection. Low IgG was not associated with severe infection (p=0.459).
Time to B cell repopulation post-RTX ranged individually but did not significantly differ between paediatric patient groups. Severe infections were non-frequent and not associated with low (post-RTX) IgG levels.
利妥昔单抗（RTX）用于治疗儿科免疫介导性疾病，可导致低丙种球蛋白血症，从而增加感染风险，但儿童中这些不良反应的数据很少。我们旨在通过时间描述儿科免疫介导性疾病中 RTX 的药效动力学来描述 B 细胞再填充，并评估 RTX 后低免疫球蛋白水平是否与感染的频率和严重程度相关。
我们回顾性收集了在我们中心接受 RTX 治疗的自身免疫性疾病（AID）、免疫失调（ID）、血液系统疾病（HD）和肾脏疾病（RD）儿童的数据，包括 RTX 前后的免疫球蛋白水平和感染发生情况。B 细胞耗竭定义为 B 细胞<10 个/μl。
在 49 例患者中，有 45 例实现了 RTX 后 B 细胞耗竭。在 30 例有 B 细胞再填充的患者中，中位再填充时间为 166 天（IQR 140-224）：AID 组（n=9）（183 天（IQR 156-239））、ID 组（n=6）（170 天（IQR 128-184））、HD 组（n=7）（139 天（IQR 127-294））、RD 组（n=7）（160 天（IQR 121-367））。7/52（13.5%）名患者发生严重感染导致住院：ID（n=3）、HD（n=1）、RD（n=3）。在 RTX 治疗后，13/52 名患者（25%）至少有一次 IgG 水平低于其年龄，11/13 名患者在 IgG 低时发生感染，但只有 2/13 名患者发生严重感染。低 IgG 与严重感染无关（p=0.459）。
RTX 后 B 细胞再填充的时间因人而异，但在儿科患者群体之间没有显著差异。严重感染并不常见，也与低（RTX 后）IgG 水平无关。
