Long-term safety of adalimumab in clinical trials in adult patients with Crohn's disease or ulcerative colitis
Long-term safety of adalimumab in clinical trials in adult patients with Crohn's disease or ulcerative colitis
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DOI：
10.1111/apt.14420
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发表时间：
2018-01-01
影响因子：
7.6
通讯作者：
Read, H.
中科院分区：
文献类型：
--
作者：
Colombel, J. -F.;Sandborn, W. J.;Read, H.
背景：阿达木单抗用于治疗常规治疗无效的中重度克罗恩病（CD）和溃疡性结肠炎（UC）。目的：更新CD和UC试验中阿达木单抗的长期安全性；既往报告仅为CD， 3160例/3402例患者年（PYs）。方法：在2/3期和3/3b期试验和开放标签扩展的成人中，治疗出现的不良事件（ae；首剂至末剂后70天/ 2015年12月31日）使用监管活动医学词典（MedDRA-v18.1）进行编码。费率以事件/100 （E/100 PYs）计算。结果：数据库（16项试验；CD， N=3606； UC， N=1739）分别代表4145和3397 PYs的暴露。对于CD，阿达木单抗的不良反应发生率为60.8%-65.1%，取决于剂量，安慰剂组为71.5%；UC的发生率分别为53.5% ~ 54.8%和56.1%。任何ae (CD, 605 E/100 PYs； UC, 361 E/100 PYs)，严重ae （CD, 36.1 E/100 PYs； UC, 18.9 E/100 PYs）和恶性肿瘤（CD, 1.2 E/100 PYs； UC, 1.0 E/100 PYs）的发生率在当前和先前的分析中相似。最近的MedDRA变化（不包括口腔念珠菌病和结核病）使CD和UC的机会性感染率分别降至0.3 E/100 PYs和0.2 E/100 PYs。恶性肿瘤的标准化发病率与一般人群相似（CD为1.45 [95% CI, 0.90-2.22]； UC为1.36 [95% CI, 0.84-2.07]）。脱髓鞘疾病不常见(CD, 0.1 E/100 PYs； UC，
Background: Adalimumab is used to treat moderate to severe Crohn's disease (CD) and ulcerative colitis (UC) when conventional therapies fail.Aim: To update long-term adalimumab safety from CD and UC trials; the previous report was CD only, 3160 patients/3402 patient-years (PYs).Methods: Treatment-emergent adverse events (AEs; first dose to 70days after last dose/December 31, 2015) in adults in phase 2/3 and 3/3b trials and open-label extensions were coded using Medical Dictionary for Regulatory Activities (MedDRA-v18.1). Rates were assessed as events/100 (E/100 PYs).Results: The database (16 trials; CD, N=3606; UC, N=1739) represented 4145 and 3397 PYs of exposure, respectively. For CD, incidences of any AEs with adalimumab were 60.8%-65.1%, depending on dose, and 71.5% with placebo; for UC, the incidences were 53.5%-54.8% and 56.1%, respectively. Rates of any AEs (CD, 605 E/100 PYs; UC, 361 E/100 PYs), serious AEs (CD, 36.1 E/100 PYs; UC, 18.9 E/100 PYs), and malignancies (CD, 1.2 E/100 PYs; UC, 1.0 E/100 PYs) were similar between current and prior analyses. Apparent rate of opportunistic infections was lowered to 0.3 and 0.2 E/100 PYs for CD and UC, respectively, by recent MedDRA changes excluding oral candidiasis and tuberculosis. Standardised incidence ratios for malignancies were similar to the general population (CD, 1.45 [95% CI, 0.90-2.22]; UC, 1.36 [95% CI, 0.84-2.07]). Demyelinating disorders were uncommon (CD, 0.1 E/100 PYs; UC,