Centre for Paediatric Rheumatology, Department of General Paediatrics, Asklepios Clinic Sankt Augustin, 53757, Sankt Augustin, Germany.
Medical Faculty, University of Cologne, Cologne, Germany.
Rheumatol Int. 2021 Apr;41(4):751-762. doi: 10.1007/s00296-020-04774-3. Epub 2021 Feb 16.
To examine whether treatment with interleukin (IL)-1-, IL-6-, tumour necrosis factor α (TNFα)-inhibitors or Abatacept is associated with an increased risk of common infections, infections requiring hospitalization (SAE) or opportunistic infections among real-world juvenile idiopathic arthritis (JIA) patients. Furthermore, the influence of other patient-related covariates on the occurrence of infections was investigated. Patients diagnosed with JIA and treated with biologics were selected from the German BIKER registry. Incidence rates (IR) of infections per 100 person years were calculated and compared between the different cohorts. Using multivariate logistic regression, odds ratios with 95% confidence intervals (CI) were determined for the influence of patient-related covariates (age, diagnosis, laboratory data, concomitant medication, JIA activity, comorbidities, and premedication) on the occurrence of infections. 3258 patients entered the analysis. A total of 3654 treatment episodes were distributed among TNFα- (Etanercept, Adalimumab, Golimumab, Infliximab, n = 3044), IL-1- (Anakinra, Canakinumab, n = 105), IL-6- (Tocilizumab, n = 400) and T-cell activation inhibitors (Abatacept, n = 105). 813 (22.2%) patients had at least one infection, 103 (2.8%) patients suffered from an SAE infection. Both common and SAE infections were significantly more frequent in IL-1 (IR 17.3, 95% CI 12.5/24 and IR 4.3, 95% CI 2.3/8.3) and IL-6 cohort (IR 16.7, 95% CI 13.9/20 and IR 2.8, 95% CI 1.8/4.4) compared to TNFα-inhibitor cohort (IR 8.7, 95% CI 8.1/9.4 and IR 1, 95% CI 0.8/1.3). When comparing the influencing factors for various infectious diseases, the use of corticosteroids, younger age, cardiac comorbidities and higher JIA-activity are the most striking risk factors. Relative to TNFα inhibitors and Abatacept, IL-1 and IL-6 inhibitors were associated with an increased risk of common and SAE infections. The influencing covariates identified may be helpful for the choice of a suitable biologic to treat JIA.
研究白细胞介素（IL）-1、IL-6、肿瘤坏死因子 α（TNFα）抑制剂或阿巴西普治疗是否会增加幼年特发性关节炎（JIA）患者的常见感染、需要住院治疗的感染（SAE）或机会性感染的风险。此外，还研究了其他与患者相关的协变量对感染发生的影响。从德国 BIKER 登记处中选择接受生物制剂治疗的 JIA 患者，计算每 100 人年的感染发生率（IR），并比较不同队列之间的感染发生率。使用多变量逻辑回归，确定与患者相关的协变量（年龄、诊断、实验室数据、合并用药、JIA 活动、合并症和预处理）对感染发生的影响的比值比（OR）及其 95%置信区间（CI）。共纳入 3258 例患者。TNFα 抑制剂（依那西普、阿达木单抗、戈利木单抗、英夫利昔单抗，n=3044）、IL-1 抑制剂（阿那白滞素、卡那单抗，n=105）、IL-6 抑制剂（托珠单抗，n=400）和 T 细胞激活抑制剂（阿巴西普，n=105）治疗中分别有 3654 个治疗周期。共有 813（22.2%）例患者至少发生一次感染，103（2.8%）例患者发生 SAE 感染。IL-1（IR 17.3，95%CI 12.5/24 和 IR 4.3，95%CI 2.3/8.3）和 IL-6 队列（IR 16.7，95%CI 13.9/20 和 IR 2.8，95%CI 1.8/4.4）的常见感染和 SAE 感染明显更常见，而 TNFα 抑制剂队列（IR 8.7，95%CI 8.1/9.4 和 IR 1，95%CI 0.8/1.3）。当比较各种传染病的影响因素时，皮质类固醇的使用、年龄较小、心脏合并症和更高的 JIA 活动是最显著的危险因素。与 TNFα 抑制剂和阿巴西普相比，IL-1 和 IL-6 抑制剂与常见感染和 SAE 感染的风险增加相关。确定的影响协变量可能有助于选择合适的生物制剂治疗 JIA。
