Liverpool Hospital and South Western Sydney Clinical School, University of New South Wales, New South Wales 2170, Australia.
Woolcock Institute of Medical Research, University of Sydney, Sydney, New South Wales 2037, Australia.
Microbiol Spectr. 2016 Dec;4(6). doi: 10.1128/microbiolspec.TNMI7-0026-2016.
Treatment with biologic agents, in particular tumor necrosis factor alpha (TNF-α) inhibitors, is associated with an increased risk of tuberculosis (TB), and screening and treatment for latent TB infection (LTBI) in patients undergoing such treatment is therefore indicated. The risk of TB associated with different biologics varies significantly, with the highest relative risks, 29.3 and 18.6, associated with adalimumab and infliximab, respectively. The risk of TB with newer TNF-α inhibitors and other biologics appears to be lower. Performance of LTBI screening tests is affected by immune-mediated inflammatory diseases and immunosuppressive therapy in patients due to commence TNF-α inhibitor treatment. Interferon gamma release assays (IGRAs) have a higher specificity than the tuberculin skin test (TST) in patients with Bacillus Calmette-Guérin (BCG) vaccination and have probably a better sensitivity than TST in immunosuppressed patients. LTBI screening programs prior to commencement of anti-TNF-α treatment significantly reduce the incidence of TB, but the optimal screening algorithm, in particular the question of whether a combination of IGRA and TST or a single test only should be used, is a matter of ongoing debate. Use of TST in combination with IGRA is justified to increase sensitivity. Repeat testing for LTBI should be limited to patients at increased risk of TB. If TB develops during anti-TNF-α treatment, it is more likely to be disseminated and extrapulmonary than are other TB cases. Discontinuation of anti-TNF-α treatment in patients diagnosed with TB is associated with an increased risk of immune reconstitution inflammatory syndrome, which is probably best managed by reintroduction of anti-TNF-α treatment.
治疗生物制剂，特别是肿瘤坏死因子-α（TNF-α）抑制剂，与结核病（TB）的风险增加有关，因此建议对接受此类治疗的患者进行潜伏性 TB 感染（LTBI）的筛查和治疗。不同生物制剂与 TB 相关的风险差异很大，阿达木单抗和英夫利昔单抗的相对风险最高，分别为 29.3 和 18.6。新型 TNF-α抑制剂和其他生物制剂的 TB 风险似乎较低。由于即将开始 TNF-α抑制剂治疗，免疫介导的炎症性疾病和免疫抑制治疗会影响 LTBI 筛查试验在患者中的性能。在接种卡介苗（BCG）的患者中，干扰素γ释放试验（IGRA）比结核菌素皮肤试验（TST）具有更高的特异性，并且在免疫抑制患者中可能比 TST 具有更好的敏感性。在开始抗-TNF-α治疗之前进行 LTBI 筛查计划可显著降低 TB 的发病率，但最佳筛查算法，特别是是否应使用 IGRA 和 TST 的组合或仅使用单一测试，是正在讨论的问题。联合使用 TST 和 IGRA 是合理的，以提高敏感性。重复 LTBI 检测应仅限于 TB 风险增加的患者。如果在抗-TNF-α治疗期间发生 TB，则更可能是播散性和肺外性的，而不是其他 TB 病例。在诊断为 TB 的患者中停用抗-TNF-α治疗与免疫重建炎症综合征的风险增加有关，这可能最好通过重新引入抗-TNF-α治疗来管理。
