4 Months of Rifampin Compared with 9 Months of Isoniazid for the Management of Latent Tuberculosis Infection: A Meta-analysis and Cost-Effectiveness Study That Focuses on Compliance and Liver Toxicity

• Published in: Clinical infectious diseases 2009-12, Vol.49 (12), p.1883-1889
• Main Authors: Ziakas, Panayiotis D., Mylonakis, Eleftherios
• Format: Article
• Language: English
• Subjects: Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antitubercular Agents - therapeutic use; ARTICLES AND COMMENTARIES; Bacterial diseases; Biological and medical sciences; Comparative analysis; Compliance costs; Cost analysis; Cost efficiency; Cost estimates; Cost-Benefit Analysis; Fees; Health Care Costs; Hematocrit; Hepatotoxicity; Human bacterial diseases; Humans; Infectious diseases; Isoniazid - adverse effects; Isoniazid - economics; Isoniazid - therapeutic use; Latent tuberculosis; Liver - drug effects; Medical sciences; Medical treatment; Medication Adherence; Meta analysis; Mycobacterium; Pharmacology. Drug treatments; Rifampin - adverse effects; Rifampin - economics; Rifampin - therapeutic use; Toxicity; Tuberculosis; Tuberculosis - drug therapy; Tuberculosis and atypical mycobacterial infections
• ISSN: 1058-4838; 1537-6591
• DOI: 10.1086/647944

Background.One-third of the world's population is infected with tuberculosis, and 9 months of isoniazid monotherapy is the treatment of choice for latent tuberculosis infection. However, this approach has been associated with hepatotoxicity and poor compliance. A shorter (4-month) rifampin regimen has been evaluated in recent clinical trials. Methods.We performed a meta-analysis of the published studies to compare compliance, toxicity, and cost-effectiveness between the 2 strategies. Pooled effects were calculated as risk ratios (RRs) by means of random-effects and fixed-effects models. Results.Pooled data from 3586 patients suggested that 4-month rifampin therapy was associated with a significant reduction in the risk of noncompletion (RR for random-effects model, 0.53; 95% confidence interval [CI], 0.44–0.63). Noncompletion rates were lower among patients who received 4-month rifampin therapy (range, 8.6%–28.4%), compared with noncompletion rates among patients who received 9-month isoniazid therapy (range, 24.1%–47.4%). Also, rates of hepatotoxicity (defined as grade 3 or 4 liver failure leading to drug discontinuation) were lower for patients who received 4-month rifampin therapy (range, 0%–0.7%), compared with the corresponding rates for patients who received 9-month isoniazid therapy (range, 1.4%–5.2%), and rifampin was associated with significant reduction in the risk of hepatotoxicity (RR for fixed-effects model, 0.12; 95% CI, 0.05–0.30). Notably, with the data from our meta-analysis, we calculated that the 4-month rifampin strategy is also cost-effective and results in $213 savings per patient treated ($90/patient when doctor fees are not included). Conclusions.The improved compliance, safety, and cost associated with the 4-month rifampin therapy suggest that the efficacy of this approach needs to be evaluated in detail. An extended posttreatment follow-up in future studies will clarify the unresolved issue of tuberculosis reactivation rates.