After almost 40 years, there's now a shorter treatment for TB

MANILA — A large-scale international study found a shorter treatment course for tuberculosis, but policy considerations, as well as drug cost and availability, could delay its implementation. The current standard treatment for people with drug-susceptible TB runs for six months and includes a combination of the drugs isoniazid, rifampin, ethambutol, and pyrazinamide. All four drugs are taken for two months, and then patients switch to isoniazid and rifampin for the remaining four months. But results of the 31/A5349 study — led by the U.S. Centers for Disease Control and Prevention’s Tuberculosis Trials Consortium and the AIDS Clinical Trials Group, with funding from the National Institute of Allergy and Infectious Diseases — found that a four-month treatment course replacing rifampin and ethambutol with high-dose rifapentine and moxifloxacin, respectively, is as safe and effective as the six-month treatment regimen in curing patients with drug-susceptible TB. At 12 months after treatment, the study found 86.8% of those who took the treatment course including rifapentine and moxifloxacin tested negative for TB. Study authors felt confident with the result, especially as a number of studies found that a vast majority of individuals were treated for TB relapse within the first six months after stopping treatment, said study co-author Dr. Susan Dorman, professor of medicine at the Medical University of South Carolina. Speaking during the 51st Union World Conference on Lung Health, she said they are carrying out an 18-month follow-up to see whether these results hold longer. A four-month TB treatment that only replaces rifampin with high-dose rifapentine was also found to be safe and well tolerated by patients in the trial, but it was not as effective as the standard six-month course, Dorman said. The study included over 2,500 participants ages 12-81 and was conducted at 34 clinical sites across 13 countries, including countries with a high TB burden such as India and South Africa. Participants included people living with HIV. Patients with drug-resistant TB were not included in the study. A shorter TB treatment could help ease the burden on patients and health workers, and it may improve patient adherence, allowing them to complete their treatment. The current standard treatment of six months is long and cumbersome, and it sometimes leads patients to drop off from therapy. Others are lost to follow-up, which not only affects their health outcomes but also could put them at risk of drug resistance. Shortening treatment has been challenging work for the TB community, and there are ongoing efforts to find a better treatment course for people who have the disease, including those with multidrug-resistant TB. This is the first successful short-course treatment regimen for drug-susceptible TB in almost 40 years, according to a news release. In Uganda, where there is a high burden of TB-HIV coinfection, the shorter treatment course of four months is exciting news for the patient community. But there are also potential challenges relating to cost and availability of the drugs when introducing this shorter treatment course, said Grace Muzanyi, senior clinical coordinator for the Tuberculosis Trials Consortium studies in Uganda. Neither rifapentine nor moxifloxacin is registered in Uganda for TB treatment or readily available, he said, adding: “Would the regimen medication be affordable in our setting, which is a resource-limited setting but also a high-TB-burden country? We are waiting to see [when this regimen] is rolled out.” There is also the question around how quickly the regimen can be deployed. A six-month TB treatment course was introduced in the 1980s but was not available in Uganda until 2015, he said. A critical next step would be the World Health Organization recommending the use of the regimen. “This rifapentine-moxifloxacin regimen meets most of the criteria that the WHO has established in its target regimen profiles for susceptible TB. And so we hope to see this taken up by the WHO and recommended for a broad use across the world,” said Richard Chaisson, professor and director at Johns Hopkins University’s Center for Tuberculosis Research.