Update on Safe, Effective Treatments for Latent Tuberculosis Infection

Isoniazid and rifampicin monotherapy and combination therapy regimens, as well as a weekly rifapentine plus isoniazid regimen, were found to be safe and effective for preventing tuberculosis (TB) reactivation among individuals with latent TB infection (LTBI). These findings from an update to a previous network meta-analysis of randomized controlled trials (RCTs) were published in the Annals of Internal Medicine.¹

Preventing reactivation of TB among individuals with LTBI is a key component to achieving the World Health Organization’s (WHO’s) End TB Strategy and the United Nations’ Sustainable Development Goal of ending the global TB epidemic by 2030. There are numerous treatment regimens for LTBI, including regimens with lower pill burdens and of shorter duration. However, more evidence is needed regarding the efficacy of the more abbreviated regimens.¹

The 2014 WHO guidelines for LTBI treatment, which provide recommendations for the least toxic and most effective regimens, are largely based on the findings from a prior network meta-analysis of RCTs.^2-4 Recently, the European Centre for Disease Prevention and Control decided to develop new guidelines on LTBI treatment. As a result, an update to the 2014 network meta-analysis was needed.¹

Dominik Zenner, MD, from the Tuberculosis Section of the Respiratory Diseases Department, Public Health England, and colleagues compared the safety and efficacy of LTBI preventative treatment regimens in an updated meta-analysis of RCTs that evaluated LTBI treatments.¹

Only RCTs that reported prespecified outcomes of active TB prevention or hepatotoxicity were eligible for analysis. Of 61 RCTs that were included, 8 were new since the previous review. All 8 new studies recorded data on TB reactivation, 4 reported data on hepatotoxicity, and 6 were conducted only in participants with HIV.¹

Monotherapy with isoniazid for 6 months (odds ratio [OR], 0.65; 95% credible interval [CrI], 0.50-0.83) or 12 to 72 months (OR, 0.50; CrI, 0.41-0.62) and monotherapy with rifampicin (OR, 0.41; CrI, 0.19-0.85) were found to be effective vs placebo.¹

Several combination regimens were also effective when compared with placebo: rifampicin plus isoniazid regimens of 3 to 4 months (OR, 0.53; CrI, 0.36-0.78), rifampicin plus pyrazinamide regimens (OR, 0.53; CrI, 0.33-0.84), and rifampicin-isoniazid-pyrazinamide regimens (OR, 0.35; CrI, 0.19-0.61). Weekly rifapentine plus isoniazid regimens also demonstrated efficacy vs no treatment (OR, 0.36; CrI, 0.18-0.73).¹

Pyrazinamide-containing regimens had higher hepatotoxicity than several isoniazid-containing regimens. Rifampicin monotherapy, rifampicin plus isoniazid, and rifapentine plus isoniazid generally had lower hepatotoxicity than isoniazid monotherapy.¹

According to Dr Zenner, these study results confirm the safety and efficacy of isoniazid monotherapy for ≥6 months, rifampicin monotherapy for 3 to 4 months, and rifampicin plus isoniazid for 3 months for LTBI. These regimens are currently recommended by the WHO and the Centers for Disease Control and Prevention, he said.

Dr Zenner also noted that the updated meta-analysis demonstrated that a 12-dose regimen of rifapentine plus isoniazid, administered once weekly over the course of 3 months, is safe and effective. A short course of treatment with a low pill burden may help address the problem of patient adherence to treatment. “This is important for clinicians who have started using [this regimen], where it is available (for example in the USA, Sweden and Norway),” he said.

References

1. Zenner D, Beer N, Harris RJ, Lipman MC, Stagg HR, van der Werf MJ. Treatment of latent tuberculosis infection: an updated network meta-analysis [published August 1, 2017]. Ann Intern Med. doi: 10.7326/M17-0609
2. Stagg HR, Zenner D, Harris RJ, Muñoz L, Lipman MC, Abubakar I. Treatment of latent tuberculosis infection: a network meta-analysis. Ann Intern Med. 2014;161:419-428.
3. Getahun H, Matteelli A, Abubakar I, et al. Management of latent Mycobacterium tuberculosis infection: WHO guidelines for low tuberculosis burden countries. Eur Respir J. 2015;46:1563-1576.
4. World Health Organization. Guidelines on the management of latent tuberculosis infection. Geneva: WHO Press; 2015.