Daily Pharmacy News

Get your free subscription started now. Just enter your email address below.

A 24-Week, All-Oral Regimen for Rifampin-Resistant Tuberculosis

In a phase 2/3 multicenter trial, a 24-week, all-oral regimen was noninferior to and safer than the currently accepted treatment for rifampin-resistant tuberculosis.

Conducted in Belarus, South Africa, and Uzbekistan, the open-label, randomized, controlled, noninferiority trial included patients aged 15 years or older with rifampin-resistant pulmonary tuberculosis. A 24-week regimen of bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM) was compared with a 9-to-20-month standard-care regimen in stage 2 of the trial. Based on a primary outcome of an unfavorable status (a composite of death, treatment failure, treatment discontinuation, loss to follow-up, or recurrence of tuberculosis) at 72 weeks after randomization, the investigators found: “Recruitment was terminated early. Of 301 patients in stage 2 of the trial, 145, 128, and 90 patients 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; 96.6% confidence interval [CI], −53 to −22). 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; 96.6% CI, −22 to 4). In the as-treated population, the incidence of adverse events of grade 3 or higher or serious adverse events was lower in the BPaLM group than in the standard-care group (19% vs. 59%).”

Editorial: “BPaLM is a welcome intermediate station on a continuing journey,” writes an editorialist. “It is imperative to keep up the momentum and use the new drug candidates in the current pipeline to create combination therapies without time-consuming detours to develop each drug separately first. This will require well-funded and efficient global consortia and determined support from a united front of patients, researchers, funders, drug developers, and public health representatives. We have a unique opportunity to come up with radically shorter and better treatment options, hopefully guided by predictive biomarkers to determine the right treatment duration for each patient. It is high time for a treatment that deserves to be called a ‘short course.'”

Source: New England Journal of Medicine