Cagatay Tulin, Bingol Zuleyha, Kıyan Esen, Yegin Zeynep, Okumus Gulfer, Arseven Orhan, Erkan Feyza, Gulbaran Ziya, Erelel Mustafa, Ece Turhan, Cagatay Penbe, Kılıçaslan Zeki
Department of Pulmonary, Istanbul Medical Faculty, Istanbul University, Istanbul, Turkey.
High School of Health Care Professions Biostatistic, Istanbul University, Istanbul, Turkey.
Clin Respir J. 2018 Apr;12(4):1668-1675. doi: 10.1111/crj.12726. Epub 2017 Nov 9.
To evaluate the characteristics of patients who developed tuberculosis while receiving tumor necrosis factor-alpha (TNF-α) antagonists and the related factors with tuberculosis.
Patient's demographics, tuberculin skin test (TST), isoniazid prophylaxis and type of TNF-α antagonist were recorded. TST conversion (≥5 mm increase) was evaluated for patients who had baseline and 1-year TST.
Files of 1887 patients who were receiving TNF-α antagonists between August 2005 and June 2015 were evaluated. TST significantly increased at the end of 1 year (n = 748 baseline:7.36 ± 7.2 mm vs. 1 year:9.52 ± 7.5 mm, P < 0.001). One-third of patients (31.2%) who had negative TST at baseline had positive TST at 1 year. Tuberculosis developed in 22 patients (1.16%). The annual incidence of tuberculosis was 423/100 000 patient-year. TNF-α antagonist indications were ankylosing spondylitis (n = 8), inflammatory bovel diseases (n = 7) and rheumatoid arthritis (n = 4). Ten (45.5%) patients received infliximab, six (27.3%) patients received etanercept and six (27.3%) patients received adalimumab. Nineteen (86.4%) patients were under isoniazid prophylaxis. Twelve patients had extrapulmonary tuberculosis (54.5%; four lymph node, three pleura, two periton, one pericarditis, one intestinal, one joint). Atypical mycobacterium was detected in one patient. Adalimumab treatment (9.5× increase), male sex (15.6× increase) and previous tuberculosis disease history (11.5× increase) were risk factors for active tuberculosis. Conversion of TST was not found related with tuberculosis.
Despite the high proportion of isoniazid prophylaxis, the incidence of tuberculosis in our patients receiving TNF-α antagonist was higher than the literature. Adalimumab treatment, male sex and previous tuberculosis disease history were found as risk factors for tuberculosis.
评估接受肿瘤坏死因子-α（TNF-α）拮抗剂治疗期间发生结核病的患者特征以及与结核病相关的因素。
记录患者的人口统计学资料、结核菌素皮肤试验（TST）、异烟肼预防用药情况及TNF-α拮抗剂类型。对有基线和1年TST结果的患者评估TST转换情况（增加≥5mm）。
对2005年8月至2015年6月期间接受TNF-α拮抗剂治疗的1887例患者的病历进行评估。1年末TST显著增加（n = 748，基线时：7.36±7.2mm vs. 1年时：9.52±7.5mm，P < 0.001）。基线时TST阴性的患者中有三分之一（31.2%）在1年时TST转为阳性。22例患者（1.1%）发生了结核病。结核病的年发病率为423/10万患者年。TNF-α拮抗剂的适应证为强直性脊柱炎（n = 8）、炎症性肠病（n = 7）和类风湿关节炎（n = 4）。10例（45.5%）患者接受英夫利昔单抗治疗，6例（27.3%）患者接受依那西普治疗，6例（27.3%）患者接受阿达木单抗治疗。19例（86.4%）患者接受了异烟肼预防用药。12例患者发生肺外结核（54.5%；4例淋巴结结核、3例胸膜炎、2例腹膜炎、1例心包炎、1例肠结核、1例关节结核）。1例患者检测到非典型分枝杆菌。阿达木单抗治疗（增加9.5倍）、男性（增加15.6倍）和既往结核病史（增加11.5倍）是活动性结核病的危险因素。未发现TST转换与结核病有关。
尽管异烟肼预防用药比例较高，但我们接受TNF-α拮抗剂治疗的患者中结核病发病率高于文献报道。发现阿达木单抗治疗、男性和既往结核病史是结核病的危险因素。
