含白细胞介素2治疗方案或可促进初治药物敏感肺结核患者早期痰培养阴转

目的:评价白细胞介素-2(IL-2)治疗初治药物敏感肺结核的有效性和安全性。方法:采用前瞻性、随机、对照、多中心临床研究方法，自2017年12月至2019年6月，于我国15个省(市)的17个研究中心连续纳入确诊的初治药物敏感肺结核患者作为研究对象，最终纳入1264例。采用计算机生成的随机化序列进行分组，619例被分配到试验组，645例被分配到对照组。试验组中有560例完成方案治疗，对照组中有591例完成方案治疗。试验组采用含IL-2(在治疗疗程的第1个月采取每日5×10⁵ U皮下注射)和异烟肼、利福平、吡嗪酰胺和乙胺丁醇的背景治疗方案；对照组仅采用异烟肼、利福平、吡嗪酰胺和乙胺丁醇治疗方案。对研究对象在6个月治疗过程中及治疗结束后的12个月内均进行包含痰菌培养和影像学评价的治疗有效性评估，以及包含药物不良反应的治疗安全性评估。结果:试验组治疗成功率为99.8%(559/560),对照组为99.3%(587/591),两组间差异无统计学意义(χ²=1.650,P=0.125)。试验组有1例(0.2%)出现不良结局(死亡);对照组有4例(0.7%...

Treatment containing interleukin-2 may improve the early sputum culture negative conversion rate in newly diagnosed and drug-susceptible pulmonary tuberculosis patients

Objective:To evaluate the efficacy and safety of interleukin-2 (IL-2) in the treatment of newly diagnosed drug-susceptible tuberculosis. Methods:A prospective, randomized, controlled and multi-center clinical research was conducted. From December 2017 to June 2019, newly diagnosed drug-sensitive pulmonary tuberculosis patients were continuously included from 17 research centers in 15 provinces (cities) of China, and 1264 cases were finally included and divided into the test group (n=619) and the control group (n=645) using computer-generated randomization sequence. In the test group, 560 cases completed the protocol treatment, and 591 cases in the control group completed the protocol treatment. The test group was treated with a background treatment regimen containing IL-2 (5×10⁵ U/d subcutaneous injection in the first month of the treatment), isoniazid, rifampicin, pyrazinamide and ethambutol; the control group was treated with isoniazid, rifampicin, pyrazinamide and ethambutol only. During the 6-month treatment and within 12 months after the end of treatment, the treatment effectiveness including sputum culture and imaging evaluation, and the treatment safety including adverse drug reactions were evaluated. Results:The treatment success rate of the test group was 99.8% (559/560), and that of the control group was 99.3% (587/591). There was no statistical difference between the two groups (χ²=1.650, P=0.125). One case (0.2%) in the test group had an adverse outcome (death); in the control group, 4 patients (0.7%) had adverse outcomes, and there were no deaths. The difference between the two groups was not statistically significant (χ²=1.650, P=0.125). After 2 months of treatment, the cavity closure rate of the test group was 28.4% (60/211), which was significantly higher than that of the control group (18.5% (46/248), and the difference was statistically significant (χ²=6.276, P=0.001). The sputum culture negative conversion rate of the test group was 96.3% (539/560), which was significantly higher than that of the control group (93.2% (551/591), and the difference was statistically significant (χ²=5.219, P=0.025). At the end of the treatment, the cavity closure rate was 61.6% (130/211) in the test group and 57.3% (142/248) in the control group, with no statistical difference (χ²=0.118, P=0.391). Within 12 months after the end of treatment, 15 patients (2.7%) in the test group relapsed, and 19 patients (3.2%) in the control group relapsed, with no statistical difference (χ²=0.298, P=0.607). Except for skin induration at the injection site, there was no significant difference in the occurrence of adverse drug reactions between the two groups. In the test group, the incidence of skin induration at the injection site was 14.8% (83/560). The most common adverse drug reactions in the two groups were hyperuricemia (the incidence rates were 23.2% (130/560) in the test group and 23.3% (138/591) in the control group). Conclusion:IL-2 containing regimen as an adjunctive treatment for newly diagnosed drug-sensitive pulmonary tuberculosis may promote the negative conversion of sputum culture and cavity closure in the early stage of treatment.