Family Medicine
Partner With Us
Advertisement
From the Journals

Oral Regimens for Rifampin-Resistant TB

"The results of the endTB trial improve prospects for effective, simple, all-oral treatment for adults and children with this disease."

Conexiant

A phase III multinational trial has confirmed the noninferiority of three all-oral regimens for treating patients with rifampin-resistant tuberculosis, offering a potential option for shortening treatment duration and improving adherence for this population.

The endTB trial involved 754 participants randomly assigned to receive either standard therapy or one of five experimental regimens, which included combinations of bedaquiline (B), delamanid (D), linezolid (L), levofloxacin (Lfx), moxifloxacin (M), clofazimine (C), and pyrazinamide (Z). The primary endpoint was a favorable outcome at week 73, defined by two negative sputum culture results or favorable bacteriologic, clinical, and radiologic evolution. Results were published in The New England Journal of Medicine.

The trial was conducted in multiple countries, including high-burden tuberculosis (TB) settings, and included 699 participants in the modified intention-to-treat analysis and 562 in the per-protocol analysis.

In the modified intention-to-treat analysis, favorable outcomes were observed in 80.7% of patients receiving standard therapy. Key findings for the most successful oral regimens included:

  • BCLLfxZ regimen: 9.8 percentage points risk difference (95% confidence interval [CI] = 0.9–18.7) compared to standard therapy.

  • BLMZ regimen: 8.3 percentage points risk difference (95% CI = −0.8 to 17.4).

  • BDLLfxZ regimen: 4.6 percentage points risk difference (95% CI = −4.9 to 14.1).

The DCMZ regimen had a risk difference of 2.5 percentage points (95% CI = −7.5 to 12.5) but did not meet the noninferiority threshold in the per-protocol analysis.

Adverse events were comparable across all regimens. Grade 3 or higher hepatotoxic events occurred in 11.7% of participants overall, with a lower incidence among those receiving standard therapy (7.1%).

"Consistent results across all the analyses support the noninferior efficacy of three all-oral shortened regimens for the treatment of rifampin-resistant [TB]," wrote first study author Lorenzo Guglielmetti, MD, of Médecins Sans Frontières and Sorbonne Université, and colleagues.

The authors noted study limitations, including the exclusion of patients with more complex forms of rifampin-resistant TB and the absence of long-term follow-up data.

"The results of the endTB trial improve prospects for effective, simple, all-oral treatment for adults and children with this disease," they concluded. 

The trial was funded by Unitaid and other international health organizations. The authors reported no conflicts of interest.