9-month, oral modified treatment regimens make the grade in drug-resistant TB

Nine-month, fully oral modified short treatment regimens (mSTRs) consisting of bedaquiline, linezolid, levofloxacin, clofazimine, and cycloserine or delamanid appear to yield high treatment success and good safety results in the treatment of patients with rifampicin-resistant, fluoroquinolone-susceptible tuberculosis (TB), according to a study.

In the treatment cohort of 2,636 patients (median age was 43 years, 74.6 percent male), the cumulative probability of not having an unsuccessful study outcome (ie, treatment failure, on-treatment loss to follow-up, death, or recurrence) 22 months after treatment initiation was 79 percent (95 percent confidence interval [CI], 78–81). [Lancet Infect Dis 2024;doi:10.1016/S1473-3099(24)00228-7]

Factors associated with unsuccessful study outcomes included increasing age (>64 years vs 35–44 years: adjusted hazard ratio [aHR], 2.61), HIV-positive status (aHR, 1.53), presence of bilateral pulmonary cavities on x-ray (aHR, 1.68), smoking history (aHR, 1.34), baseline anaemia (aHR, 1.46), unemployment (aHR, 1.37), elevated baseline liver enzymes (aHR, 1.40), and excessive alcohol use (aHR, 1.47).

“We found that end-of-treatment success rates with mSTRs were higher than those of the WHO-recommended fully oral STR (74 percent), reported in an observational cohort study in South Africa, and the 9-month all-oral regimen containing delamanid, linezolid, levofloxacin, and pyrazinamide (78 percent), studied in a randomized controlled trial in South Korea,” the investigators noted.

“The cumulative probability of not having an unsuccessful study outcome 22 months after treatment initiation with an mSTR was also higher than the sustained treatment success with either the WHO-recommended STR or delamanid-based 9-month regimen,” they added.

With regard to safety of the mSTRs, 301 adverse events of interest (grade ≥3 severity) occurred in 252 (9.0 percent) participants, for an incidence rate of 1.32 (95 percent CI, 1.18–1.48) per 100 person-months. Myelosuppression was the most frequently reported (4.9 percent), followed by QTcF interval prolongation (1.7 percent), and peripheral neuropathy (1.1 percent). The median time to onset of adverse event of interest was 98 days. A total of 2,813 patients comprised the safety cohort.

“The peak of severe adverse events of interest in the third month of treatment provides a crucial temporal insight that might inform clinical monitoring practices and patient-management strategies… Our findings contribute to a growing body of evidence that reinforces the therapeutic potential of these regimens and underscores the need for vigilant monitoring of adverse events of interest to mitigate risks and enhance patient safety,” the investigators said.

In the study, the patients who participated were from 13 countries in the WHO European region. Patients aged 6 years or older received one of two regimens: bedaquiline, linezolid, levofloxacin, clofazimine, and cycloserine or bedaquiline, linezolid, levofloxacin, clofazimine, and delamanid. Patients not more than 5 years of age were given delamanid, linezolid, levofloxacin, and clofazimine. All of them were followed up for 12 months after successful treatment completion to monitor recurrence and death.

“High rates of treatment success and high probability of not having unsuccessful study outcomes indicate good potential for use of an mSTR under programmatic conditions. The three regimens evaluated here will broaden national tuberculosis programs’ regimen choices, particularly for individuals not eligible for the current WHO-recommended 6-month regimen (ie, people who are pregnant or breastfeeding, and children aged <14 years) and in settings with limited access to pretomanid,” according to the investigators.

“These mSTRs could help to facilitate WHO’s End TB Strategy goal of a 90-percent treatment success rate for all forms of tuberculosis by 2030,” they said.