© Médecins Sans Frontières
v2.1.4829.produseast1
© Médecins Sans Frontières
v2.1.4829.produseast1
The World Health Organization estimates that 410,000 people developed a drug-resistant tuberculosis infection (DR-TB) in 2022, only 40% of whom were diagnosed and started on treatment—and only 63% then cured. Given all these points of failure, innovation in preventing, diagnosing and treating DR-TB cannot come fast enough.
To mark World TB Day (24 March 2024) the content collection linked below highlights recent work by MSF and collaborators to help change this grim picture. The TB-PRACTECAL and endTB studies delivered robust evidence for shorter, safer, more effective drug regimens that are already saving lives worldwide. Other studies explore new approaches to preventive treatment and simpler, quicker, accurate detection of TB and drug resistance—especially among difficult-to-diagnose populations such as children and people living with HIV.
But to impact DR-TB globally these innovations must become widely accessible. This requires changes on many fronts, as described in an accompanying Collection (Expanding Access to Lifesaving New TB Tools).
BACKGROUND
After a history of poor treatments for rifampin-resistant tuberculosis (RR-TB), recent advances have resulted in shorter, more effective treatments. However, they are not available to everyone and have shortcomings, requiring additional treatment options.
METHODS
endTB is an international, open-label, Phase 3 non-inferiority, randomized, controlled clinical trial to compare five 9-month all-oral regimens including bedaquiline (B), delamanid (D), linezolid (L), levofloxacin (Lfx) or moxifloxacin (M), clofazimine (C) and pyrazinamide (Z), to the standard (control) for treatment of fluoroquinolone-susceptible RR-TB. Participants were randomized to 9BLMZ, 9BCLLfxZ, 9BDLLfxZ, 9DCLLfxZ, 9DCMZ and control using Bayesian response-adaptive randomization. The primary outcome was favorable outcome at week 73 defined by two negative sputum culture results or by favorable bacteriologic, clinical and radiologic evolution. The non-inferiority margin was 12 percentage points.
RESULTS
Of 754 randomized patients, 696 and 559 were included in the modified intention to treat (mITT) and per-protocol (PP) analyses, respectively. In mITT, the control had 80.7% favorable outcomes. Regimens 9BCLLfxZ [adjusted risk difference (aRD): 9.5% (95% confidence interval (CI), 0.4 to 18.6)], 9BLMZ [aRD: 8.8% (95%CI, −0.6 to 18.2)], and 9BDLLfxZ [3.9% (95%CI, −5.8 to 13.6)] were non-inferior in mITT and in PP. The proportion of participants experiencing grade 3 or higher adverse events was similar across the regimens. Grade 3 or higher hepatotoxicity occurred in 11.7% of the experimental regimens overall and in 7.1% of the control.
CONCLUSIONS
The endTB trial increases treatment options for RR-TB with three shortened, all-oral regimens that were non-inferior to a current well-performing standard of care.