Department of Rheumatology, Teaching Hospital Lapeyronie, University of Montpellier, Montpellier.
Department of Rheumatology, Teaching Hospital Purpan, and University of Paul Sabatier, Toulouse.
Rheumatology (Oxford). 2017 Oct 1;56(10):1746-1754. doi: 10.1093/rheumatology/kex238.
Observational studies have already reported the risk of serious infections in RA treated with tocilizumab, but in limited samples. The aim of this study was to investigate the predictive risk factors for serious infections in the largest European registry of patients treated with tocilizumab for RA.
A total of 1491 RA patients included in the French REGistry-RoAcTEmra were analysed to calculate the incidence rate of first serious infections rate after initiation of tocilizumab. To identify independent factors associated with serious infections, a Cox model was performed.
Among the 1491 patients, average age 56.6 (13.6) years, 125 serious infections occurred in 122 patients (incidence rate of serious infection: 4.7/100 patient-years). Univariate analysis identified initial ACPA positivity as the only factor associated with a lower risk of serious infection [hazard ratio (HR) = 0.56, 95% CI: 0.36, 0.88]. Other factors significantly associated with a higher risk of serious infections were DAS28, concomitant Leflunomide (LEF) treatment, and absolute neutrophil count (ANC) at baseline. Initial ANC above 5.0 × 109/l (HR = 1.94, 95% CI: 1.32, 2.85; P < 0.001), negative ACPA (HR = 1.79, 95% CI: 1.15, 2.78; P = 0.012) at baseline and concomitant LEF treatment (LEF alone vs no treatment, HR = 2.18, 95% CI: 1.22, 3.88; P = 0.009) remained significantly associated with first serious infections in multivariate analysis after imputation for missing data.
The rate of first serious infections in current practice is similar to that reported in clinical trials. High ANC (above 5.0 × 109 at baseline), negative ACPA and concomitant therapy with LEF are predictive factors of serious infection, requiring in this case a tighter surveillance.
观察性研究已经报告了托珠单抗治疗类风湿关节炎（RA）患者发生严重感染的风险，但样本有限。本研究旨在调查最大的欧洲托珠单抗治疗 RA 患者登记处中，严重感染的预测风险因素。
对纳入法国 REGistry-RoAcTEmra 的 1491 例 RA 患者进行分析，以计算托珠单抗治疗后首次严重感染的发生率。为了确定与严重感染相关的独立因素，进行了 Cox 模型分析。
在 1491 例患者中，平均年龄 56.6（13.6）岁，122 例患者发生 125 例严重感染（严重感染发生率：4.7/100 患者年）。单因素分析发现初始 ACPA 阳性是唯一与严重感染风险降低相关的因素[风险比（HR）=0.56，95%置信区间：0.36，0.88]。其他与严重感染风险增加显著相关的因素是 DAS28、同时使用来氟米特（LEF）治疗和基线时的绝对中性粒细胞计数（ANC）。基线时 ANC 高于 5.0×109/L（HR=1.94，95%置信区间：1.32，2.85；P<0.001）、初始时 ANC 阴性（HR=1.79，95%置信区间：1.15，2.78；P=0.012）和同时使用 LEF 治疗（LEF 单独治疗与无治疗相比，HR=2.18，95%置信区间：1.22，3.88；P=0.009）在缺失数据的多变量分析中仍与首次严重感染显著相关。
目前实践中的首次严重感染发生率与临床试验报告的相似。高 ANC（基线时高于 5.0×109/L）、阴性 ACPA 和同时使用 LEF 是严重感染的预测因素，在这种情况下需要更密切的监测。
