Risk of Herpes Zoster in Patients With Rheumatoid Arthritis Treated With Anti-TNF-α Agents
Risk of Herpes Zoster in Patients With Rheumatoid Arthritis Treated With Anti-TNF-α Agents
复制标题
DOI：
10.1001/jama.2009.146
复制
发表时间：
2009-02-18
影响因子：
120.7
通讯作者：
Zink, Angela
中科院分区：
文献类型：
--
作者：
Strangfeld, Anja;Listing, Joachim;Zink, Angela
使用抑制肿瘤坏死因子α (TNF- α)药物治疗的患者发生细菌感染的风险增加。对TNF- α抑制剂治疗期间潜伏病毒感染的再激活知之甚少。目的探讨TNF- α抑制剂作为一类或单独作为单克隆抗TNF- α抗体（阿达木单抗、英夫利昔单抗）或融合蛋白（依那西普）是否与类风湿关节炎患者较高的带状疱疹发病率有关。设计、环境和患者：在2001年5月至2006年12月期间，在开始使用英夫利昔单抗、依那西普、阿达木单抗或阿那那单抗治疗时，或当他们改变传统的疾病修饰抗风湿药物（DMARD）时，患者被纳入德国生物制剂登记处RABBIT，这是一个前瞻性队列。治疗、临床状况和不良事件由风湿病学家在随访期间的固定时间点进行评估。主要结局指标抗TNF- α治疗后带状疱疹发作的风险比（HR）。研究目的是检测TNF- α抑制剂作为一类与DMARDs相比的临床显著差异（HR, 2.0），并检测两种类型的TNF- α抑制剂，单克隆抗体或融合蛋白与常规DMARDs相比的HR至少为2.5。结果在5040例接受TNF- α抑制剂或常规DMARDs治疗的患者中，82例患者发生86次带状疱疹发作。39例可归因于抗TNF- α抗体治疗，23例归因于依那西普治疗，24例归因于常规dmard治疗。单克隆抗体的粗发病率为11.1(95%可信区间[CI]， 7.9- 15.1)，依那西普为8.9 (95% CI, 5.6-13.3)，传统dmard为5.6 （95% CI, 3.6- 8.3）。经年龄、类风湿关节炎严重程度和糖皮质激素使用调整后，单克隆抗体治疗的风险显著增加（HR, 1.82 [95% CI, 1.05- 3.15]），尽管该风险低于具有临床意义的阈值。依那西普的使用（HR, 1.36 [95% CI, 0.73-2.55]）和抗TNF- α治疗（HR, 1.63 [95% CI, 0.97- 2.74]）作为一个类别没有发现显著关联。结论单克隆抗TNF- α抗体治疗可能与带状疱疹风险增加有关，但这需要进一步研究。
Context The risk of bacterial infection is increased in patients treated with drugs that inhibit tumor necrosis factor alpha ( TNF- alpha). Little is known about the reactivation of latent viral infections during treatment with TNF- alpha inhibitors.Objective To investigate whether TNF- alpha inhibitors together as a class, or separately as either monoclonal anti-TNF-alpha antibodies (adalimumab, infliximab) or a fusion protein ( etanercept), are related to higher rates of herpes zoster in patients with rheumatoid arthritis.Design, Setting, and Patients Patients were enrolled in the German biologics register RABBIT, a prospective cohort, between May 2001 and December 2006 at the initiation of treatment with infliximab, etanercept, adalimumab, or anakinra, or when they changed conventional disease- modifying antirheumatic drug ( DMARD). Treatment, clinical status, and adverse events were assessed by rheumatologists at fixed points during follow- up.Main Outcome Measures Hazard ratio ( HR) of herpes zoster episodes following anti - TNF- alpha treatment. Study aims were to detect a clinically significant difference ( HR, 2.0) between TNF- alpha inhibitors as a class compared with DMARDs and to detect an HR of at least 2.5 for each of 2 types of TNF- alpha inhibitors, the monoclonal antibodies or the fusion protein, compared with conventional DMARDs.Results Among 5040 patients receiving TNF- alpha inhibitors or conventional DMARDs, 86 episodes of herpes zoster occurred in 82 patients. Thirty- nine occurrences could be attributed to treatment with anti - TNF- alpha antibodies, 23 to etanercept, and 24 to conventional DMARDs. The crude incidence rate per 1000 patient- years was 11.1 ( 95% confidence interval [ CI], 7.9- 15.1) for the monoclonal antibodies, 8.9 ( 95% CI, 5.6-13.3) for etanercept, and 5.6 ( 95% CI, 3.6- 8.3) for conventional DMARDs. Adjusted for age, rheumatoid arthritis severity, and glucocorticoid use, a significantly increased risk was observed for treatment with the monoclonal antibodies ( HR, 1.82 [ 95% CI, 1.05- 3.15]), although this risk was lower than the threshold for clinical significance. No significant associations were found for etanercept use ( HR, 1.36 [ 95% CI, 0.73-2.55]) or for anti - TNF- alpha treatment ( HR, 1.63 [ 95% CI, 0.97- 2.74]) as a class.Conclusion Treatment with monoclonal anti - TNF- alpha antibodies may be associated with increased risk of herpes zoster, but this requires further study.