Fewer Pills Plus Shorter Time: New Way to Control Drug-Resistant TB?

Three investigational drug regimens to treat drug-resistant tuberculosis (TB) were superior to standard of care, with fewer unfavorable outcomes and a shorter treatment time, a researcher said.

In a modified intention-to-treat analysis, a lower proportion of patients with rifampicin-resistant TB who were randomized to one of the three investigational regimen arms experienced an unfavorable outcome after 72 weeks compared with patients randomized to standard of care (11% to 23% vs 48%, respectively), reported Bern-Thomas Nyang'wa, MD, of Doctors Without Borders in Amsterdam, at the virtual Conference on Retroviruses and Opportunistic Infections (CROI).

All three regimens exceeded the planned noninferiority margin of 12% to achieve superiority over standard of care.

Nyang'wa explained that the current standard of care for rifampicin-resistant TB consists of 15 to 20 pills a day for a minimum of 9 months, and potentially up to 2 years, while all three investigative regimens in this study contained four to six pills per day taken for 6 months.

"Shorter duration, lower pill burden, less toxic. All those things we learned for HIV," said Elaine Abrams, MD, of Columbia University Irving Medical Center in New York City, who moderated the press conference.

Nyang'wa also noted that current standard-of-care treatment for rifampin-resistant TB is often toxic, and only has a 60% success rate.

"It really is a big step in terms of ... patients being able to take a treatment that is less toxic and more [friendly] in terms of pill burden and frequency," he added.

The phase II/III Pragmatic Clinical Trial for a More Effective Concise and Less Toxic MDR-TB Treatment Regimen (TB-PRACTECAL) examined the safety and efficacy of three 24-week oral regimens for rifampin-resistant TB. This multiyear trial included participants ages 15 and up from Uzbekistan, Belarus, and South Africa. Enrollment began in January 2017, but was discontinued in March 2021 when the trial was terminated early for benefit, the authors said.

Participants were randomized to one of three investigational arms or the control arm:

• Bedaquiline, pretomanid, and linezolid (BPaL)
• Bedaquiline, pretomanid, linezolid, and clofazimine (BPaLC)
• Bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM)

Overall, there were 286 participants in the modified intention-to-treat population. Among the four arms, 33% to 47% were female, and 25% to 33% had HIV. Participants in the three investigational arms received four to six pills per day, while the standard-of-care control arm received 20 per day.

Nyang'wa noted that the BPaLM arm had the highest percentage of patients without an unfavorable outcome (89%), followed by the BPaLC arm (81%) and the BPaL arm (77%) compared with 52% of the control arm.

Three participants in the BPaL arm had recurrences, one occurred in the BPaLC arm, and none occurred in the BPaLM arm. One participant in the BPaLC arm died, two died in the control arm, and none died in the BPaL or BPaLM arms.

Approximately 59% of participants in the control arm experienced at least one grade ≥3 and/or serious adverse event versus 21.7%, 31.9%, and 19.4% in the BPaL, BPaLC, and BPaLM arms, respectively.

The researchers have shared their data with the WHO for an upcoming drug-resistant TB guidelines review, and also plan to share it with more national TB programs, Nyang'wa said.

"We believe the data we're sharing has the potential to impact global policy change," he added.

Comment