Key message
- The BPaLM regimen (bedaquiline, pretomanide, linezolide, moxifloxacin) lasting 24 weeks is not inferior to the standard treatment of 9-20 months for the treatment of rifampicin-resistant tuberculosis.
A study funded by Médecins Sans Frontières shows that the BPaLM regimen (bedaquiline, pretomanide, linezolide, moxifloxacin) is not inferior to standard treatment for rifampicin-resistant tuberculosis.Data published in New England Journal of Medicine show that 89% of patients treated with the BPaLM regimen have favorable outcomes. The advantages of the proposed regimen are numerous: drugs are administered exclusively orally, treatment has a shorter duration (6 months instead of 9-20 months), and the safety profile is better. All this could improve adherence to treatment, a major problem in the management of tuberculosis, and increase the chances of success.
The phase 2/3 TB-PRACTECAL study enrolled 552 patients (age>15 years) in Belarus, Uzbekistan and South Africa. Participants were randomized to receive standard care or one of three investigational regimens: BPaLM, BPaL (bedaquiline, pretomanid, linezolide), or BPaLC (bedaquiline, pretomanid, linezolide, clofazimine); The goal of stage 1 was to identify the regimen for continuation of the study based on safety and efficacy 8 weeks after randomisation.In stage 2, 301 patients were treated with standard care or the BPaLM regimen. The primary outcome was an unfavorable condition (death, treatment failure, treatment discontinuation, loss at follow-up, or relapse) at 72 weeks after randomisation.
The proportion of patients with bacteriological conversion at 8 weeks was 77% with BPaLM, 67% with BPaLC and 46% with BPaL; 8%, 6% and 10% of patients in the same groups had discontinued treatment or died; for stage 2, the BPaLM regimen was therefore selected. In the modified treatment intention analysis, 11% of patients in the BPaLM group and 48% of those in the control group had an unfavorable condition. In the analysis by protocol, the percentages were, respectively, 4% and 12%. The results made it possible to establish the non-inferiority of the new regime compared to the standard regime. The incidence of grade ≥3 adverse events was 19% in the BPaLM group and 59% in the control group.
In an editorial Andreas H.Diacon, who directs the Task Applied Science and Task Foundation in Cape Town, South Africa, an institution specializing in clinical and microbiological research on tuberculosis, acknowledges that this is a great success. However, the expert points out some critical aspects that could make this achievement short-lived. First, bedaquiline’s patent is about to expire and the uncontrolled use of poor quality generics could compromise its effectiveness. The mechanism of action of pretomanid makes it vulnerable to the appearance of resistance. Linezolid should be monitored for possible toxicity. Finally, 30% of patients in certain areas already have quinolone-resistant tuberculosis. «The BPaLM regimen is a welcome intermediate station on a journey that continues,» he writes, «It is critical not to lose speed and use the new drugs that are being developed to create combination therapies without first developing each drug separately, time-wasting detours.This will require well-funded and efficient global consortia and the staunch support of a united front of patients, researchers, funders, drug developers and public health representatives.»
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Source — https://www.univadis.it/viewarticle/bastano-6-mesi-di-regime-orale-curare-la-tubercolosi-2022a10028sw