Shorter Tuberculosis Regimen With Moxifloxacin Not Inferior to 6-Month Treatment

NEW YORK (Reuters Health) – A new rifapentine-based regimen with moxifloxacin can shorten the treatment time for drug-susceptible pulmonary tuberculosis, the authors behind a new phase-3 test report.

“This is the first time in 40 years wherein treatment shortening has been feasible for drug-susceptible TB, so this is a landmark event,” coauthor Dr. Payam Nahid, director of the Center for Tuberculosis at the University of California, San Francisco, told Reuters Health by phone.

The open-label noninferiority study, published in the New England Journal of Medicine, shows that after a four-month regimen of rifapentine, isoniazid, pyrazinamide and moxifloxacin, 15.5% of participants had an unfavorable outcome at the 12-month mark.

The rate was 14.6% in patients randomly assigned to receive a standard six-month regimen of rifampin, isoniazid, pyrazinamide and ethambutol (difference, 1.0 percentage point; 95% confidence interval, -2.6 to 4.5).

With another four-month regimen, in which ethambutol replaced moxifloxacin, the rate was 17.7%, which was considered inferior to the standard regimen.

During the treatment period, 18.8% of patients getting moxifloxacin had an adverse event of grade 3 or higher compared to 19.3% in the control group. The side effect rate in the less-effective treatment group was 14.3%.

The study has established “an important principle: there is no magic with 6 months of therapy. We do not know what the biologic limits of therapy are, but it might be possible to get to shorter regimens,” say Dr. Eric Rubin of the Harvard T.H. Chan School of Public Health, in Boston, and Dr. Valerie Mizrahi of the University of Cape Town in a linked editorial.

Tuberculosis has long been the leading cause of infectious-disease death worldwide, claiming about 1.5 million lives per year, a fact that people often forget, said Dr. Nahid.

That changed with the pandemic, he noted, but “with vaccines I think, sadly, TB will take its pole position once again.”

The study involved 2,343 volunteers age 12 or older treated at 34 sites worldwide. Culture tests showed that their TB was susceptible to isoniazid, rifampin and fluoroquinolones. Some of the volunteers – 8% – were HIV positive, but they needed a CD4 T-cell count of at least 100 cells/mm3 to be eligible. The patients were followed for 18 months.

“What continues to surprise me is the robustness of the results of this trial wherein in any analysis population we looked at, any sensitivity analysis we looked at, we found the same finding — that the four-month regimen was not inferior to the standard six-month regiment, and was safe and well tolerated,” said Dr. Nahid.

The World Health Organization is reviewing the new regimen and “I hope uptake would be rapid,” he said. “I wouldn’t know why they wouldn’t adopt a four-month regimen that was deemed to be as efficacious, safe and tolerable as the six-month regimen. If I were a patient, I would want to know about it.”

A formal cost-effectiveness analysis of the two therapies is underway, the researcher said. The drug combination is more expensive but the shorter duration may result in savings, including the fact that patients can get on with their lives sooner.

Sanofi donated all study drugs, supported the shipment of the trial drugs to the sites, and provided funding support for pharmacokinetic testing and preparation of the final clinical study report. One of Dr. Nahid’s coauthors receives consulting fees from the company.

SOURCE: and The New England Journal of Medicine, online May 5, 2021.

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