In 2021, the WHO Global TB Programme received data from the Study 31 investigators and convened a Guideline Development Group (GDG) to review study results. The GDG meeting took place as an online meeting from 27-30 April 2021. Detailed results from Study 31 were published on 6 May 2021 (4).
The objectives of the GDG meeting were to review the evidence on the efficacy and safety of a 4-month regimen for the treatment of drug-susceptible TB and update evidence-informed recommendations on the optimal use of regimens for the treatment of drug-susceptible TB. Based on the outcomes of the GDG meeting, detailed recommendations will be presented in the 2021 update of the WHO consolidated guidelines on tuberculosis. Module 4: Treatment – Drug-Susceptible Tuberculosis Treatment.
This rapid communication aims to inform national TB programmes, technical partners and other stakeholders about the key findings and considerations on the use of the 4-month regimen following the assessment of new evidence, in order to allow for planning at the country level.
Study 31 was a randomized, multi-national, open-label, controlled phase 3 trial comparing two 4-month rifapentine-containing regimens to the standard 6-month control regimen. The intervention considered by the WHO convened GDG was a 4-month regimen composed of rifapentine, isoniazid, pyrazinamide and moxifloxacin. The other 4-month regimen composed of rifapentine, isoniazid, ethambutol and pyrazinamide did not meet non-inferiority criteria and therefore was not reviewed by the GDG. The trial enrolled participants who were 12 years or older with newly diagnosed pulmonary tuberculosis confirmed by a WHO recommended diagnostic test and who were susceptible to isoniazid, rifampicin and the fluoroquinolones. The primary efficacy outcome was tuberculosis disease-free survival at 12 months after randomization. The efficacy of the 4-month rifapentine-based regimen containing moxifloxacin was non-inferior to the standard 6-month regimen for the treatment of drug-susceptible pulmonary tuberculosis and the regimen was equally well tolerated.
The available evidence reviewed by the GDG on the 4-month regimen for treatment of drug-susceptible pulmonary TB supports the use of this regimen as a possible alternative to the current standard 6-month regimen. The shorter regimen has showed similar performance to the current standard regimen, both in terms of efficacy and safety. The 4-month regimen, which is shorter, effective and all-oral, would be a preference for many patients and also national TB programmes, allowing faster cure and easing the burden on both patients and the healthcare system. However, implementation and uptake of the new regimen in the short to medium term will be more feasible if the cost of rifapentine is reduced and availability improved. It will also require rigorous antibacterial stewardship to ensure the appropriate use of the first-line regimen given that it contains moxifloxacin, an antibiotic usually used for the treatment of drug-resistant TB.
Based on the outcomes of the GDG meeting, detailed recommendations will be presented in the 2021 update of the WHO consolidated guidelines on tuberculosis. Module 4: Treatment – Drug-Susceptible Tuberculosis Treatment.