The effects of anti-inflammatory agents as host-directed adjunct treatment of tuberculosis in humans: a systematic review and meta-analysis.

BACKGROUND The potential role of adjunctive anti-inflammatory therapy to enhance tuberculosis (TB) treatment has recently received increasing interest. There is, therefore, a need to broadly examine current host-directed therapies (HDTs) that could accelerate treatment response and improve TB outcomes. METHODS This systematic review and meta-analysis included randomised controlled trials of vitamin D and other HDT agents in patients receiving antibiotic treatment for pulmonary TB. Sputum smear conversion rate at 4-8 weeks was the primary outcome. Secondary outcomes included blood indices associated with infectivity and inflammation, chest radiology and incidence of adverse events. RESULTS Fifty-five studies were screened for eligibility after the initial search, which yielded more than 1000 records. Of the 2540 participants in the 15 trials included in the meta-analysis, 1898 (74.7%) were male, and the age at entry ranged from 18 to 70 years. There was a 38% significantly (RR 1.38, 95% CI = 1.03-1.84) increased sputum smear negativity in patients administered with vitamin D in addition to standard TB treatment than those receiving only the TB treatment. Patients treated with other HDT anti-inflammatory agents in addition to TB treatment also had a 29% significantly increased sputum smear conversion rate (RR 1.29, 95% CI = 1.09-1.563). Lymphocyte to monocyte ratio was significantly higher in the vitamin D treatment groups compared to the controls (3.52 vs 2.70, 95% CI for difference 0.16-1.11, p = 0.009) and (adjusted mean difference 0.4, 95% CI 0.2 -- 0.6; p = 0.001); whilst tumour necrosis factor-alpha (TNF-α) showed a trend towards a reduction in prednisolone (p < 0.001) and pentoxifylline (p = 0.27) treatment groups. Vitamin D and N-acetylcysteine also accelerated radiographic resolution in treatment compared to placebo at 8 weeks. No differences were observed in the occurrence of adverse events among all HDT treatments. CONCLUSIONS Vitamin D and other anti-inflammatory HDT medications used as adjunct TB treatment may be well tolerated and effective. They significantly improved sputum smear conversion rate and chest radiological appearance, and also exhibited an inflammation resolution effect.