Abstract:

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.

Key words: Tuberculosis, pulmonary, Interleukin-2, Therapeutic uses, Randomized controlled trial