24-week regimen of bedaquiline, pretomanid, linezolid, and moxifloxacin bests standard-care treatment for rifampin-resistant tuberculosis
Standard-care treatment was similarly efficacious when patients could receive it without adverse effects, according to findings from a two-stage, phase 2–3 clinical trial.
Delhi: A 24-week all-oral regimen of bedaquiline, pretomanid, linezolid, and moxifloxacin was shown to be non-inferior to the accepted standard-care treatment in patients with rifampin-resistant pulmonary tuberculosis and had a better safety profile in a recent study.
The study findings were featured in the New England Journal of Medicine.
Worldwide in 2019, about 465,000 patients were affected by rifampin-resistant tuberculosis. 59% of the patients with rifampin-resistant tuberculosis who began treatment initiation in 2018 have had successful outcomes, and there was not much improvement in this incidence in the past five years.
The main challenges include social disruption, adverse events, and cost. These shortcomings led to the need for more effective, shorter treatments with a more acceptable side-effect profile than the current regimens. In programmatic care settings, the recommended treatment duration is 9 to 20 months and involves up to 20 tablets per day.
Against the above background, Bern-Thomas Nyang'wa and colleagues aimed to examine the safety and efficacy of 24-week, all-oral regimens for treating rifampin-resistant tuberculosis in a two-stage, phase 2–3 clinical trial, TB-PRACTECAL (Pragmatic Clinical Trial for a more Effective, Concise and Less Toxic Regimen).
The authors enrolled patients in Uzbekistan, South Africa, and Belarus who were 15 years of age and above and had rifampin-resistant pulmonary tuberculosis. In trial stage 2, a comparison was made between a 24-week regimen of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) and a 9-to-20-month standard-care regimen. Unfavourable status (primary outcome) was described as a composite of treatment failure, death, loss to follow-up, treatment discontinuation, or recurrent tuberculosis at 72 weeks after randomization. The noninferiority margin was 12 percentage points.
The study led to the following findings:
- Recruitment was terminated early. Of 301 patients in stage 2 of the trial, 145, 128, and 90 were evaluable in the intention-to-treat, modified intention-to-treat, and per-protocol populations, respectively.
- In the modified intention-to-treat analysis, 11% of the patients in the BPaLM group and 48% of those in the standard care group had a primary-outcome event (risk difference, −37 percentage points).
- In the per-protocol analysis, 4% of the patients in the BPaLM group and 12% of those in the standard care group had a primary-outcome event (risk difference, −9 percentage points).
- In the as-treated population, the incidence of grade 3 or higher adverse events or serious adverse events was lower in the BPaLM group than in the standard care group (19% vs. 59%).
Findings indicate that BPaLM was both non-inferior and superior to the accepted standard care concerning the primary composite outcome; 89% and 52% of the patients, respectively, had favourable results.
Also, the percentage of patients with favourable outcomes in the BPaL group (77%) and the BPaLC group (81%) was more significant than in the standard care group. The difference was driven mainly by early treatment discontinuation due to adverse events in the standard-care group. The difference between the standard-care and investigational groups was less noticeable in the per-protocol analysis, where early discontinuations were excluded.
"These findings suggest that the standard-care treatment was similarly efficacious when patients could receive it without adverse effects," the authors concluded.
Reference:
The study "24-Week, All-Oral Regimen for Rifampin-Resistant Tuberculosis" was published in the New England Journal of Medicine.
DOI: 10.1056/NEJMoa2117166
