Adjunctive therapy with interferon-gamma for the treatment of pulmonary tuberculosis: a systematic review

OBJECTIVE: To evaluate the efficacy and safety of adjunctive therapy using interferon-gamma (IFN-γ; an immunomodulator) for the treatment of pulmonary tuberculosis (TB). METHODS: We conducted a systematic review of controlled clinical trials that compared anti-TB drugs in combination with IFN-γ with the same anti-TB drugs alone for the treatment of pulmonary TB. RESULTS: Nine trials were identified, with IFN-γ being aerosolized or administered subcutaneously in one trial, aerosolized only in five trials, and administered intramuscularly in three trials. The methodology quality of all trials was rated ‘C’. Meta-analysis of the trials with aerosolized IFN-γ showed statistical benefits on sputum negative conversion and chest radiograph: the pooled relative risk (RR) for conversion was 1.97 (95% confidence interval (CI) 1.20–3.24, p=0.008) after 1 month of treatment, 1.74 (95% CI 1.30–2.34, p=0.0002) after 2 months of treatment, 1.53 (95% CI 1.16–2.01, p=0.003) after 3 months of treatment, 1.57 (95% CI 1.20–2.06, p=0.001) after 6 months of treatment, and 1.55 (95% CI 1.17–2.05, p=0.002) at the end of treatment; the pooled RR for the chest radiograph was 1.38 (95% CI 1.10–1.17, p=0.006) at the end of treatment. For intramuscularly administered IFN-γ, meta-analysis of three trials showed its significant improvement on sputum negative conversion after 2 months of treatment. A randomized controlled trial with aerosolized and subcutaneously administered IFN-γ reported significant reductions in the symptoms of fever, wheeze, and night sweats in the IFN-γ-treated groups compared with the control group after 1 month of treatment. No patients discontinued treatment because of adverse effects caused by IFN-γ. CONCLUSION: Adjuvant therapy using IFN-γ, especially by aerosol, might be beneficial to TB patients, but large randomized controlled trials are needed for further evaluation of its efficacy and safety considering the quality of the trials analyzed.