Drug-specific risk of non-tuberculosis opportunistic infections in patients receiving anti-TNF therapy reported to the 3-year prospective French RATIO registry
Drug-specific risk of non-tuberculosis opportunistic infections in patients receiving anti-TNF therapy reported to the 3-year prospective French RATIO registry
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DOI：
10.1136/ard.2010.137422
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发表时间：
2011-04-01
影响因子：
27.4
通讯作者：
Mariette, X.
中科院分区：
文献类型：
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作者：
Salmon-Ceron, D.;Tubach, F.;Mariette, X.
背景抗肿瘤坏死因子（TNF）治疗可能与机会性感染（OIs）有关。目的描述抗TNF治疗相关的非结核性OIs的谱，并确定其危险因素。方法法国国家注册中心（RATIO）3年收集了法国接受抗TNF治疗的任何适应症患者的所有OI病例。结果在43例接受英夫利昔单抗（n=29）、阿达木单抗（n=10）或依那西普（n=4）治疗的患者中收集了45例非结核性OI，用于治疗类风湿性关节炎（n=26）、脊柱关节炎（n=3）、炎症性结肠炎（n=8）、银屑病（n=1）或其他疾病（n=5）。三分之一（33%）的OI为细菌性（4例绦虫病、4例诺卡氏菌病、4例非典型分枝杆菌病、3例非伤寒沙门氏菌病），40%为病毒性（8例严重带状疱疹、3例水痘、3例广泛单纯疱疹、4例播散性巨细胞病毒感染），22%为真菌性（5例肺囊虫病、3例侵袭性曲霉病、2例隐球菌病），4%为寄生虫性（2例利什曼病）。10名患者（23%）需要入住重症监护室，4名患者（9%）死亡。OI的风险因素为英夫利西单抗治疗（OR=17.6（95% CI 4.3 - 72.9）; p < 0.0001）或阿达木单抗（OR=10.0（2.3至44.4）; p=0.002）与依那西普相比，并且在过去一年中口服类固醇使用> 10 mg/天或静脉推注结论抗TNF治疗可导致多种严重的OIs，尤其是细胞内微生物感染。单克隆抗TNF抗体而不是可溶性TNF受体治疗和类固醇使用> 10 mg/天与OI独立相关。
Background Anti-tumour necrosis factor (TNF) therapy may be associated with opportunistic infections (OIs).Objective To describe the spectrum of non-tuberculosis OIs associated with anti-TNF therapy and identify their risk factors.Methods A 3-year national French registry (RATIO) collected all cases of OI in patients receiving anti-TNF treatment for any indication in France. A case-control study was performed with three controls treated with anti-TNF agents per case, matched for gender and underlying inflammatory disease.Results 45 cases were collected of non-TB OIs in 43 patients receiving infliximab (n=29), adalimumab (n=10) or etanercept (n=4) for rheumatoid arthritis (n=26), spondyloarthritides (n=3), inflammatory colitis (n=8), psoriasis (n=1) or other conditions (n=5). One-third (33%) of OIs were bacterial (4 listeriosis, 4 nocardiosis, 4 atypical mycobacteriosis, 3 non-typhoid salmonellosis), 40% were viral (8 severe herpes zoster, 3 varicella, 3 extensive herpes simplex, 4 disseminated cytomegalovirus infections), 22% were fungal (5 pneumocystosis, 3 invasive aspergillosis, 2 cryptococcosis) and 4% were parasitic (2 leishmaniasis). Ten patients (23%) required admission to the intensive care unit, and four patients (9%) died. Risk factors for OIs were treatment with infliximab (OR=17.6 (95% CI 4.3 - 72.9); p < 0.0001) or adalimumab (OR=10.0 (2.3 to 44.4); p=0.002) versus etanercept, and oral steroid use > 10 mg/day or intravenous boluses during the previous year (OR=6.3 (2.0 to 20.0); p=0.002).Conclusion Various and severe OIs, especially those with intracellular micro-organisms, may develop in patients receiving anti-TNF treatment. Monoclonal anti-TNF antibody rather than soluble TNF receptor therapy and steroid use > 10 mg/day are independently associated with OI.