VAIL, COLO. – Results of a landmark study of a far simpler and more convenient treatment regimen for latent tuberculosis infection are expected to transform clinical pediatric practice in relatively short order, Dr. John W. Ogle said.
The Centers for Disease Control and Prevention–sponsored PREVENT TB trial included 8,053 participants with latent TB, of whom nearly 1,000 were children older than age 2 years. Participants were randomized to either the standard treatment regimen of daily self-administered isoniazid for 9 months, or a novel regimen consisting of directly observed therapy with isoniazid (INH) and rifapentine (INN) once-weekly for 3 months. With 33 months of follow-up, the new regimen was as effective in preventing cases of active TB as was the standard regimen. However, the once-weekly therapy had significantly better adherence and fewer side effects, which was not surprising given that it entailed only 12 total doses of medication, compared with 270 doses in the standard regimen.
The soon-to-be-published study was presented earlier this year in Denver at a meeting of the American Thoracic Society. The CDC has called the PREVENT TB findings "one of the most significant advances in TB research in decades." An expert panel has been convened to analyze the data and begin working on new U.S. treatment guidelines.
The shorter-course regimen appeared to be as effective as standard therapy in children as well as in adults. The increased rate of hepatitis and other isoniazid-related side effects that is seen with standard therapy was more striking in adults than in children, but that’s to be expected because adults typically have more toxicities than do children, Dr. Ogle observed at a conference on pediatric infectious diseases sponsored by Children’s Hospital Colorado.
"It’s very likely that we’re going to be urged to adopt this INH/INN regimen as routine therapy because it’s so much easier," predicted Dr. Ogle, professor of pediatrics at the University of Colorado at Denver and director of pediatric services at Denver Health Medical Center.
That being said, he urged his pediatric colleagues to remain vigilant as they adopt the anticipated new guidelines.
"When this regimen is broadened to a bigger population, we’ll undoubtedly learn new things. That’s what always happens when you take a moderately or even a big-powered study and adopt it in another population. No one knows the incidence of side effects in the general population. We’ve seen a couple of kids who’ve had rifapentine reactions," Dr. Ogle said.
As an aside, Dr. Ogle noted that he hasn’t prescribed liquid isoniazid in more than 10 years. "I’ve found it to be a reliable way to give a child diarrhea. We’ll crush the tablets instead, even down to a 1-month-old infant," he said.
Dr. Ogle declared having no relevant financial disclosures.