Risk for lower intestinal perforations in patients with rheumatoid arthritis treated with tocilizumab in comparison to treatment with other biologic or conventional synthetic DMARDs.
Risk for lower intestinal perforations in patients with rheumatoid arthritis treated with tocilizumab in comparison to treatment with other biologic or conventional synthetic DMARDs.
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DOI：
10.1136/annrheumdis-2016-209773
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发表时间：
2017-03
影响因子：
27.4
通讯作者：
Listing J
中科院分区：
文献类型：
--
作者：
Strangfeld A;Richter A;Siegmund B;Herzer P;Rockwitz K;Demary W;Aringer M;Meißner Y;Zink A;Listing J
研究tocilizumab （TCZ）治疗的类风湿关节炎（RA）患者发生下肠穿孔（LIPs）的风险。在德国生物制剂登记的13310例类风湿关节炎：生物治疗的观察中，截至2015年10月31日，报告了141例可能与穿孔相关的严重胃肠道事件。所有事件均由两名医生独立验证，治疗暴露盲法。在53 972患者年（PYs）中观察到37例lip（32例在结肠/sigma）。仅有2例患者有憩室炎病史（1例在TCZ）。年龄、当前/累积的糖皮质激素和非甾体抗炎药与LIP的风险显著相关。与其他治疗组（0.2 ~ 0.6/1000 PYs）相比，TCZ组LIP的粗发生率显著升高（2.7/1000 PYs）。在TCZ中，调整后的HR（参考：常规合成（cs）改善疾病的抗风湿药物（DMARDs））为4.48 (95% CI 2.0至10.0)，在肿瘤坏死因子-α抑制剂（TNFi）中为1.04(0.5至2.3)，在其他生物DMARDs中为0.33（0.1至1.4）。4/11患者经TCZ治疗后未出现典型的LIP（急腹症，剧烈疼痛）症状。只有1例患者C反应蛋白（CRP）高度升高。1 / 4的患者在LIP后30天内死亡（9/37），TCZ组为5/11，TNFi组为2/13，csDMARD组为2/11。在这项现实世界的研究中发现，TCZ组的LIP发病率与TCZ的随机对照试验一致，并且高于所有其他DMARD治疗。为了确保TCZ在日常实践中的安全使用，医生和患者应该意识到，在TCZ下，LIP可能仅出现轻微症状，而不会出现CRP升高。
To investigate the risk of developing lower intestinal perforations (LIPs) in patients with rheumatoid arthritis (RA) treated with tocilizumab (TCZ). In 13 310 patients with RA observed in the German biologics register Rheumatoid Arthritis: Observation of Biologic Therapy, 141 serious gastrointestinal events possibly associated with perforations were reported until 31 October 2015. All events were validated independently by two physicians, blinded for treatment exposure. 37 LIPs (32 in the colon/sigma) were observed in 53 972 patient years (PYs). Only two patients had a history of diverticulitis (one in TCZ). Age, current/cumulative glucocorticoids and non-steroidal anti-inflammatory drugs were significantly associated with the risk of LIP. The crude incidence rate of LIP was significantly increased in TCZ (2.7/1000 PYs) as compared with all other treatments (0.2−0.6/1000 PYs). The adjusted HR (ref: conventional synthetic (cs) disease-modifying anti-rheumatic drugs (DMARDs)) in TCZ was 4.48 (95% CI 2.0 to 10.0), in tumour necrosis factor-α inhibitor (TNFi) 1.04 (0.5 to 2.3) and in other biologic DMARDs 0.33 (0.1 to 1.4). 4/11 patients treated with TCZ presented without typical symptoms of LIP (acute abdomen, severe pain). Only one patient had highly elevated C reactive protein (CRP). One quarter of patients died within 30 days after LIP (9/37), 5/11 under TCZ, 2/13 under TNFi and 2/11 under csDMARD treatment. The incidence rates of LIP under TCZ found in this real world study are in line with those seen in randomised controlled trials of TCZ and higher than in all other DMARD treatments. To ensure safe use of TCZ in daily practice, physicians and patients should be aware that, under TCZ, LIP may occur with mild symptoms only and without CRP elevation.