Shorter TB Regimen Matched Standard Care in Rifampicin-Resistant Disease

A 6-month tuberculosis (TB) treatment regimen delivered similar results to the longer standard-of-care regimen in patients with pulmonary rifampicin-resistant TB, a phase III noninferiority trial showed.

Among 402 patients, 86.1% of those who received 6 months of bedaquiline (Sirturo), delamanid, linezolid, and levofloxacin or clofazimine or both had a successful outcome — defined as cure or completion of treatment — compared with 86.0% of those who received seven drugs for 9 months (P=0.001 for noninferiority), reported Francesca Conradie, MBBCh, of the Jose Pearson TB Hospital in Bethelsdorp, South Africa, and colleagues in the New England Journal of Medicine.

These results from the BEAT Tuberculosis trial give clinicians another simple, all-oral, 6-month option for drug-resistant TB that can be used even in children and pregnant or breastfeeding women, Conradie told MedPage Today.

The regimen’s simplicity is its strength, she noted. “A regimen that can be used across households and across key populations is much easier to implement in routine care,” she said. Because very few people were excluded from the trial, Conradie added, it “provides evidence that is directly relevant to real-world clinical practice and to the patients whom TB programs treat every day.”

Clinical practice guidelines issued last year by the American Thoracic Society, the CDC, the European Respiratory Society, and the Infectious Diseases Society of America recommended a 6-month regimen of bedaquiline, pretomanid, linezolid, and moxifloxacin in patients ages 14 years and older with pulmonary rifampin-resistant, fluoroquinolone-susceptible TB.

But this regimen isn’t for everyone, Conradie said, given that pretomanid is contraindicated in younger children and in people who are pregnant or breastfeeding. “This matters because TB transmission often occurs within households, and a simple, unified household approach to treatment can support adherence and implementation,” she explained.

The trial’s results have already reshaped WHO recommendations, Conradie noted. In patients with multidrug- or rifampicin-resistant TB, the WHO’s updated TB treatment guidelines now support a 6-month regimen of bedaquiline, linezolid, delamanid, levofloxacin, and clofazimine with or without fluoroquinolone resistance.

For this study, the researchers enrolled patients ages 6 years and older in South Africa between August 2019 and October 2022. Patients were eligible if they had pulmonary TB with resistance to rifampicin with or without resistance to isoniazid or fluoroquinolones (or both). Women who were pregnant or breastfeeding were included.

Among the included patients, median age was 35 years (7.4% were under 18), 42.2% were female, 76.9% were Black, 50.9% had HIV infection, and 5.3% were pregnant at baseline. One in five patients (21.1%) was resistant to fluoroquinolone, and 6.3% were resistant to bedaquiline.

The study’s primary endpoint of a successful outcome was defined as cure or completion of treatment at the end of treatment and at 76 weeks after randomization.

Grade 3 or higher adverse events occurred in 31.2% of the shorter-treatment group and 37.0% of the standard-treatment group. Ten patients in each group died.

The two groups were similar when comparing those who finished the trial with both a successful outcome and without any grade 3 or higher adverse events (60.9% versus 57.5%, respectively.)

All pregnancies resulted in singleton live births, and all children had successful outcomes at the end of treatment and the 76-week monitoring period.

There were no apparent differences between the two groups in the time to a stable negative culture conversion or in fluoroquinolone susceptibility, nor did treatment effects appear to vary by age, sex, HIV status, baseline sputum smear status, chest radiography cavities, or fluoroquinolone resistance.

Study limitations included the single-country location, which could limit the findings’ generalizability in other regions with different TB resistance patterns and HIV prevalence rates.