Université Paris Descartes, Sorbonne Paris Cité, IHU Imagine, APHP, Hôpital Necker Enfants malades, Centre d'Infectiologie Necker Pasteur, Service de maladies infectieuses et tropicales, Paris.
Université Paris Diderot, Sorbonne Paris Cité, UFR de médecine, Paris; APHP, Hôpital Bichat, Département d'Epidémiologie et Recherche Clinique, Paris; INSERM, CIE 801, Paris.
Chest. 2013 Sep;144(3):990-998. doi: 10.1378/chest.12-2820.
Our objective was to describe the incidence and risk factors of legionellosis associated with tumor necrosis factor (TNF)-α antagonist use.
From February 1, 2004, to January 31, 2007, we prospectively collected all cases of legionellosis among French patients receiving TNF-α antagonists in the Research Axed on Tolerance of Biotherapies (RATIO) national registry. We conducted an incidence study with the French population as a reference and a case-control analysis with four control subjects receiving TNF-α antagonists per case of legionellosis.
Twenty-seven cases of legionellosis were reported. The overall annual incidence rate of legionellosis for patients receiving TNF-α antagonists, adjusted for age and sex, was 46.7 (95% CI, 0.0-125.7) per 100,000 patient-years. The overall standardized incidence ratio (SIR) was 13.1 (95% CI, 9.0-19.1; P < .0001) and was higher for patients receiving infliximab (SIR, 15.3 [95% CI, 8.5-27.6; P < .0001]) or adalimumab (SIR, 37.7 [95% CI, 21.9-64.9; P < .0001]) than etanercept (SIR, 3.0 [95% CI, 1.00-9.2; P = .06]). In the case-control analysis, exposure to adalimumab (OR, 8.7 [95% CI, 2.1-35.1]) or infliximab (OR, 9.2 [95% CI, 1.9-45.4]) vs etanercept was an independent risk factor for legionellosis.
The incidence rate of legionellosis for patients receiving TNF-α antagonists is high, and the risk is higher for patients receiving anti-TNF-α monoclonal antibodies than soluble TNF-receptor therapy. In case of pneumonia occurring during TNF-α antagonist therapy, specific urine antigen detection should be performed and antibiotic therapy should cover legionellosis.
ClinicalTrials.gov; No.: NCT00224562; URL: www.clinicaltrials.gov.
本研究旨在描述肿瘤坏死因子（TNF）-α拮抗剂治疗相关军团菌病的发病情况及危险因素。
从 2004 年 2 月 1 日至 2007 年 1 月 31 日，我们前瞻性地收集了法国接受 TNF-α拮抗剂治疗的患者中军团菌病的所有病例，该研究纳入了研究耐受生物疗法（RATIO）国家注册数据库。我们进行了发病率研究，以法国人群为参考，并进行了病例对照分析，每例军团菌病患者设 4 例对照。
共报告 27 例军团菌病。接受 TNF-α拮抗剂治疗的患者军团病的年调整发病率为 46.7（95%可信区间，0.0-125.7）/10 万患者年。总的标准化发病比（SIR）为 13.1（95%可信区间，9.0-19.1；P <.0001），接受英夫利昔单抗（SIR，15.3 [95%可信区间，8.5-27.6；P <.0001]）或阿达木单抗（SIR，37.7 [95%可信区间，21.9-64.9；P <.0001]）治疗的患者 SIR 高于接受依那西普（SIR，3.0 [95%可信区间，1.00-9.2；P =.06]）。在病例对照分析中，阿达木单抗（OR，8.7 [95%可信区间，2.1-35.1]）或英夫利昔单抗（OR，9.2 [95%可信区间，1.9-45.4]）暴露是军团菌病的独立危险因素。
接受 TNF-α拮抗剂治疗的患者军团病的发病率较高，且接受抗 TNF-α单克隆抗体治疗的患者的风险高于接受可溶性 TNF 受体治疗的患者。在 TNF-α拮抗剂治疗期间发生肺炎时，应进行特异性尿液抗原检测，抗生素治疗应覆盖军团菌病。
ClinicalTrials.gov；注册号：NCT00224562；网址：www.clinicaltrials.gov。
