Efficacy and safety of a four-drug fixed-dose combination regimen versus separate drugs for treatment of pulmonary tuberculosis: a systematic review and meta-analysis.

INTRODUCTION: Tuberculosis, particularly multi-drug-resistant tuberculosis, is a major cause of morbidity and mortality worldwide. To the best of our knowledge, however, no study to date has assessed the combined use of the four available drugs for tuberculosis treatment, which is an issue of great clinical relevance.

OBJECTIVE: To determine whether the four-drug fixed-dose combination is safer or more effective than separate drugs for treatment of pulmonary tuberculosis.

METHODS: A systematic review of the literature was performed in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines.

RESULTS: In pooled results from five randomized controlled trials with 3502 patients across Africa, Asia, and Latin America, four-drug fixed-dose combination therapy was no better than separate drugs therapy in terms of culture conversion after 2 and 6 months of treatment. There were no significant differences between the groups in overall incidence of adverse effects. However, the meta-analytic measure (log odds ratio) revealed that separate drugs treatment had a 1.65 [exp (0.5)=1.65] increased chance of gastrointestinal adverse effects compared to four-drug fixed-dose combination treatment.

CONCLUSIONS: The reviewed studies showed that four-drug fixed-dose combination therapy provides greater patient comfort by reducing the number of pills and the incidence of gastrointestinal adverse effects, as well as simplifying pharmaceutical management at all levels.