Department of Medicine and Therapeutics, Institute of Digestive Disease, Chinese University of Hong Kong, Hong Kong, China.
Department of Medicine and Therapeutics, Division of Infectious Disease, Chinese University of Hong Kong, Hong Kong, China.
J Crohns Colitis. 2018 Jul 30;12(8):954-962. doi: 10.1093/ecco-jcc/jjy057.
Biologic therapies have revolutionised the treatment of immune-mediated diseases including inflammatory bowel disease [IBD] and rheumatological disorders. However, biologic treatments are associated with an increased risk of reactivation of latent tuberculosis. Data from regular monitoring for latent tuberculosis infection [LTBI] during biologic treatment are lacking.
Consecutive patients eligible for biologic therapies were screened for LTBI and prospectively followed up for 3 years. Incidence and risk factors of latent tuberculosis tests conversion (interferon gamma release assays [IGRA], tuberculin skin tests [TST], and chest radiography [CXR]) with clinical outcomes were studied.
A total of 108 patients [83 IBD; 25 rheumatological disorders] were included. At baseline, 18/108 [16.7%] patients [five IBD; 13 rheumatological disorders] were tested positive for LTBI. Of these, 14/18 [77.8%] patients received isoniazid monotherapy for 9 months. Of the remainder, 17/90 [18.9%] patients had LTBI test conversion while on biologic therapies and of these 14/17 [82.4%] received isoniazid monotherapy for 9 months. Age, sex, smoking status, alcohol use, travel history, disease type, and immunosuppressive therapy were not associated with LTBI test conversion. In subjects with IGRA conversion, serial IGRA levels normalised after completion of isoniazid except in one patient whose IGRA remained persistently elevated despite isoniazid and who subsequently developed active TB.
Conversion of LTBI is common and occurred early during biologic therapy in an area with intermediate TB burden. Subjects with latent TB tests conversion and persistently high IGRA levels may have an increased risk of TB reactivation or development of active TB, and they require close observation or intensive workup for active TB.
生物疗法已经彻底改变了免疫介导性疾病的治疗方法,包括炎症性肠病[IBD]和风湿性疾病。然而,生物疗法与潜伏性结核再激活的风险增加有关。在生物治疗期间进行常规潜伏性结核感染[LTBI]监测的数据尚缺乏。
连续筛选适合生物治疗的患者进行 LTBI 筛查,并前瞻性随访 3 年。研究潜伏性结核试验转换(干扰素释放试验[IGRA]、结核菌素皮肤试验[TST]和胸部 X 线[CXR])的发生率和危险因素,以及临床结局。
共纳入 108 例患者[83 例 IBD;25 例风湿性疾病]。基线时,18/108 例患者[5 例 IBD;13 例风湿性疾病]LTBI 检测呈阳性。其中,14/18 例患者[77.8%]接受异烟肼单药治疗 9 个月。其余 17/90 例患者在接受生物治疗期间 LTBI 检测呈阳性,其中 14/17 例患者[82.4%]接受异烟肼单药治疗 9 个月。年龄、性别、吸烟状况、饮酒史、旅行史、疾病类型和免疫抑制治疗与 LTBI 检测转换无关。在 IGRA 转换的患者中,异烟肼治疗后连续 IGRA 水平恢复正常,除了 1 例患者的 IGRA 持续升高,尽管接受了异烟肼治疗,仍发展为活动性结核病。
在结核病负担中等的地区,LTBI 转换在生物治疗早期很常见。潜伏性结核试验转换和持续高 IGRA 水平的患者可能有结核再激活或发生活动性结核病的风险增加,需要密切观察或进行活动性结核病的强化检查。