抗TNF治疗使带状疱疹风险增加75%

抗TNF治疗使带状疱疹风险增加75%

柏林——欧洲风湿病学大会上公布的一项Meta分析显示，接受抗肿瘤坏死因子(TNF)治疗的炎性类风湿疾病患者发生带状疱疹的风险，是接受缓解疾病抗风湿药物(DMARD)治疗者的近2倍。

Cedric Lukas博士

尽管已知抗TNF药物可能导致细菌感染风险增加，但尚不清楚其是否也增加病毒感染风险。为此，法国蒙彼利埃lapeyronie医院风湿科的Cedric Lukas博士及其同事进行了一项Meta分析，对2002~2010年发表的655篇论文和134篇会议摘要进行了回顾，最终纳入22篇论文和28篇摘要。所研究的抗TNF药物包括依那西普(恩利)、阿达木单抗(修美乐)和英夫利昔单抗(类克)。

该Meta分析的数据来源于美国、英国和其他欧洲国家，包括BSRBR(英国风湿病学会生物制剂注册库)、BIOBADASER(西班牙生物制剂治疗风湿性疾病的不良事件注册库), CORRONA(北美风湿病学研究联合会)、McDonald美国退伍军人队列(Clin. Infect. Dis. 2009;48:1364-71)和RABBIT(德国生物制剂治疗类风湿关节炎观察)。在对适当治疗方案和疾病进行选择后，共对124, 966患者-年的数据进行了分析。Lukas博士等人在不同注册中观察到相似趋势，并且不同数据来源之间无显著异质性。

该Meta分析显示，接受抗TNF抑制剂治疗的炎性类风湿疾病患者的总体带状疱疹感染风险增至75%。总体而言，接受抗TNF治疗的患者发生带状疱疹的汇总比值比(OR)为1.75(95% CI，1.50~2.04)，这一风险几乎是接受DMARD治疗者的2倍。根据注册库划分的OR如下：BIOBADASER，2.45；BSRBR，1.45；CORRONA，2.34；McDonald，1.33；RABBIT，1.82。

除了Meta分析之外，研究者还使用3个注册库的数据，专门探讨了是否有某些抗TNF药物与较高风险相关。1个注册库的数据显示英夫利昔单抗的风险稍高，但另外2项研究显示所有抗TNF药物的风险相似。在McDonald注册库中，英夫利昔单抗(OR，1.32；95%CI，0.85~2.03)的风险高于依那西普(OR，0.62；95%CI，0.40~0.95)和阿达木单抗(OR，0.53；95%CI，0.31~0.91)。

研究者表示，其实临床上已观察到这些患者易发生带状疱疹，而且有相应的预防措施。在美国，目前有预防带状疱疹的疫苗可供60岁以上老年人或带状疱疹高危者使用。对于这些患者，在治疗开始前，可以考虑接种疫苗。由于这是一种活疫苗，因此应在抗TNF治疗开始前1个月接种。在欧洲，目前这种疫苗尚未上市，因此需要对患者进行预防治疗。

Lukas博士声明无相关经济利益冲突。该研究从法国雅培公司获得无限制教育资金支持。

爱思唯尔  版权所有

By: BECKY MCCALL, Internal Medicine News Digital Network

BERLIN – Patients who have inflammatory rheumatic diseases and are on anti–tumor necrosis factor therapy have nearly double the risk of herpes zoster when they are compared with patients on disease-modifying antirheumatic drugs, according to the first meta-analysis in these patient populations.

Although the risk of bacterial infection is known to be increased among patients on anti-TNF therapy, less well known is whether the use of anti-TNF agents increases the risk for viral infections, especially herpes zoster, said Dr. Cedric Lukas of the department of rheumatology at Lapeyronie Hospital in Montpellier, France.
 
The meta-analysis of literature that was published between 2002 and 2010 involved a review of 655 articles and 134 congress abstracts, of which 22 articles and 28 abstracts eventually were included in the study. The anti-TNF therapies that were investigated included etanercept (Enbrel), adalimumab (Humira), and infliximab (Remicade), which were the agents available at the time.

National registries from the United States, United Kingdom, and other European countries were included in the meta-analysis, including BSRBR (British Society for Rheumatology Biologics Register), BIOBADASER (Spanish Registry of Adverse Events of Biological Therapies in Rheumatic Diseases), CORRONA (Consortium of Rheumatology Researchers of North America), the McDonald cohort of U.S. veterans (Clin. Infect. Dis. 2009;48:1364-71), and RABBIT (the German Rheumatoid Arthritis Observation of Biologic Therapy) were selected for inclusion. After selection for appropriate treatment regimens and diseases, 124, 966 patient years were included.

Upon meta-analysis, Dr. Lukas showed that there was a similar trend across the different registries, and no significant heterogeneity among data sources.

The meta-analysis showed an overall increased risk of herpes zoster infection up to 75% in patients whose inflammatory rheumatic diseases were treated with anti-TNF inhibitors. Overall, the pooled odds ratio for herpes zoster infection with anti-TNF therapy was 1.75 (95% confidence interval, 1.50-2.04). This was almost a twofold risk of developing disease with these drugs compared with DMARDs, Dr. Lukas said at the annual European Congress of Rheumatology.

Odds ratios by national registries were BIOBADASER, 2.45; BSRBR, 1.45; CORRONA, 2.34; McDonald, 1.33; and RABBIT, 1.82.

In addition to the meta-analysis, investigators used data from three registries specifically to determine whether the use of any particular anti-TNF drug was associated with a higher risk. "We found that one registry showed [that] infliximab had a somewhat higher risk, but this was only one out of three studies. The other two studies showed a similar risk across all anti-TNF agents."

In the McDonald registry, the risk was found to e higher with infliximab (OR, 1.32; 95% CI, 0.85-2.03) compared with etanercept (OR, 0.62; 95% CI, 0.40-0.95) and adalimumab (OR 0.53; 95% CI, 0.31-0.91).

"We already knew that these patients were prone to herpes zoster; we see the lesions in clinics." But there are preventive measures available that one can take, he said.

In the United States, there are vaccines to prevent herpes zoster, which are available to people who are older than age 60 years, or are at high specific risk of developing herpes zoster infection. "In these patients, we could think about vaccines before treatment is started," pointed out Dr. Lukas. "It is a live vaccine so it should be given a month before start of anti-TNF therapy. In Europe, where the vaccine is unavailable, we need to give patients prophylaxis."

Dr. Lukas reported no relevant conflicts of interest. The study was supported by an unrestricted educational grant from Abbott France.