肿瘤坏死因子拮抗剂治疗类风湿关节炎和强直性脊柱炎发生结核的风险

Risk of tuberculosis in rheumatoid arthritis and ankylosing spondylitis patients treated with tumor necrosis factor antagonists

目的了解类风湿关节炎(RA)和强直性脊柱炎(AS)患者在应用肿瘤坏死因子(TNF)拮抗剂治疗前后结核病的发病风险。方法随访2003年7月至2006年2月期间进行英利昔单抗和依那西普临床试验的RA和AS患者,筛选时对所有患者均进行结核菌素纯蛋白衍生物(PPD)皮试及拍摄胸部正侧位X线片．随访过程中密切观察结核的发生情况。结果筛选的67例RA患者中1例PPD阳生,英利昔单抗治疗结束后发生右锁骨上淋巴结结核1例；203例AS筛选患者中27例PPD阳性,2例胸部X线片发现肺部结核钙化灶．2例为肺部结核,入选AS患者试验期间及随访过程中均无结核病发生。临床试验筛选的RA和AS患者的PPD阳性及胸片显示结核活动或有钙化灶的统计数据显示均低于我国全人口的结核感染率和活动性肺结核患病率。其差异有统计学意义(P＜0．01)。结论本研究未发现RA和AS患者接受抗TNF治疗前后结核发病的风险的增高,但在应用TNF拮抗剂治疗前,建议应严格掌握适应证,避免严重不良反应的发生。

Objective To study the risk of tuberculosis （TB） infection in rheumatoid arthritis （RA） and ankylosing spondylitis （AS） patients before and after treated with tumor necrosis factor （TNF） antagonists. Methods RA and AS patients treated with TNF antagonists infliximab and etanercept between 2003 and 2006 were followed up for the risk of TB infection. The protein purified derivative （PPD） test and chest anteroposterior and lateral view X-ray were clone at screening for all these patients. Results Among 67 RA patients screened, 1 was PPD positive. One patient developed right supraclavicular lymph node TB 4 months after study completion. Among 203 AS patients screened, 27 patients were PPD positive, 2 had calcified pulmonary TB foci and 2 had pulmonary TB. PPD positive rates and calcified TB foci or active TB found in RA and AS patients screened were significantly lower than national TB infection rates and prevalence （P〈0.01）. Conclusion In this short-term clinical observation, increased risk of TB infection was not found after TNF antagonists treatment in RA and AS patients. However, it is necessary to screen patients for signs of TB infection before TNF antagonists treatment.