Department of Population Medicine, Harvard Medical School & Harvard Pilgrim Health Care Institute.
Pediatric Rheumatology.
Rheumatology (Oxford). 2022 Apr 11;61(4):1610-1620. doi: 10.1093/rheumatology/keab626.
To investigate the incidence and risk factors for hypogammaglobulinaemia and infectious complications associated with rituximab treatment in childhood-onset rheumatic diseases.
We performed a single-centre retrospective study of patients (n = 85) treated at Boston Children's Hospital (BCH) from 2009 to 2019. Study subjects included patients (ages 6-24 years) who received rituximab for the treatment of a childhood-onset rheumatic disease.
New-onset hypogammaglobulinaemia developed in 23 (27.1%) patients within 18 months of rituximab induction treatment. Twenty-two patients (25.9%) developed at least one infectious complication in the 18 months following the first rituximab infusion; of these, 11 (50%) had serious infections requiring inpatient treatment. After adjusting for potential confounders, exposure to pulse corticosteroid therapy in the month prior to rituximab use was a significant predictor of both new-onset hypogammaglobulinaemia (odds ratio [OR] 3.94; 95% CI: 1.07, 16.0; P = 0.044) and infectious complications (OR 15.3; 95% CI: 3.04, 126.8; P = 0.003). Post-rituximab hypogammaglobulinaemia was the strongest predictor of serious infectious complications (OR 7.89; 95% CI: 1.41, 65.6; P = 0.028). Younger age at rituximab use was also a significant predictor of new-onset hypogammaglobulinaemia (OR 0.83; 95% CI: 0.70, 0.97; P = 0.021). Compared with other rheumatic diseases, patients with vasculitis had a higher likelihood of developing infectious complications, including serious infections.
Although rituximab was well tolerated in terms of infectious complications in the majority of patients with childhood-onset rheumatic diseases, a substantial proportion developed new-onset hypogammaglobulinaemia and infectious complications following treatment. Our study highlights a role for heightened vigilance of rituximab-associated hypogammaglobulinaemia and infections in paediatric patients with rheumatic conditions.
调查儿童发病的风湿性疾病患者接受利妥昔单抗治疗后发生低丙种球蛋白血症和感染并发症的发生率及相关风险因素。
我们对 2009 年至 2019 年在波士顿儿童医院（BCH）接受治疗的 85 例患者进行了单中心回顾性研究。研究对象包括接受利妥昔单抗治疗儿童发病的风湿性疾病的患者（年龄 6-24 岁）。
在利妥昔单抗诱导治疗后 18 个月内，23 例（27.1%）患者新出现低丙种球蛋白血症。在首次利妥昔单抗输注后 18 个月内，22 例（25.9%）患者发生至少 1 次感染并发症；其中 11 例（50%）需要住院治疗的严重感染。在校正潜在混杂因素后，利妥昔单抗使用前 1 个月接受脉冲皮质类固醇治疗是新出现低丙种球蛋白血症（比值比 [OR] 3.94；95%置信区间：1.07，16.0；P=0.044）和感染并发症（OR 15.3；95%置信区间：3.04，126.8；P=0.003）的显著预测因素。利妥昔单抗后低丙种球蛋白血症是严重感染并发症的最强预测因素（OR 7.89；95%置信区间：1.41，65.6；P=0.028）。利妥昔单抗使用时年龄较小也是新出现低丙种球蛋白血症的显著预测因素（OR 0.83；95%置信区间：0.70，0.97；P=0.021）。与其他风湿性疾病相比，血管炎患者发生感染并发症（包括严重感染）的可能性更高。
尽管在大多数儿童发病的风湿性疾病患者中，利妥昔单抗在感染并发症方面具有良好的耐受性，但相当一部分患者在治疗后出现新的低丙种球蛋白血症和感染并发症。我们的研究强调了在风湿性疾病患儿中对利妥昔单抗相关低丙种球蛋白血症和感染进行高度警惕的作用。
