Study: New TB drug may reduce treatment to once a week for most patients
June 1, 2000 4 minutes read
Study: New TB drug may reduce treatment to once a week for most patients
Cavitary disease, culture positivity remain risk factors
For a substantial proportion of TB patients — probably about 45% — a once-weekly regimen incorporating a 600 mg dose of rifapentine can be safely substituted for biweekly therapy during the continuation phase of therapy.
The findings appear to confirm what TB experts have been hoping: that rifapentine’s long half-life makes fewer doses possible, reducing not only inconvenience to patients but costs to programs as well.
By screening outpatients with cavitation on their chest X-rays, clinicians can get results "almost equal" to standard therapy, says Andy Vernon, MD, medical epidemiologist at the Division of TB Elimination (DTBE) of the Centers for Disease Control and Prevention (CDC) in Atlanta, and project officer for the TB Trials Consortium, the agency based at the DTBE that has been doing the trials.
Using a different factor as a filter — sputum culture positivity at two months — also works, but not quite as well, Vernon adds.
Either way, it’s important that patients selected for the new regimen get "good, solid induction," he emphasizes. That doesn’t mean all candidates have to be model citizens, they just need to be capable of good compliance, he adds. "The patients enrolled in our trial had higher-than-average rates of alcoholism, homelessness, and drug abuse, but they were enrolled because they were judged to be people who could complete therapy and follow-up. They all got a full and robust induction according to current recommendations."
The importance of induction appears to be underscored by results of an earlier trial carried out by the drug’s manufacturer, Vernon says. That trial showed more problems associated with the rifapentine regimen. The reason, many researchers think, might be because some patients in the earlier trial didn’t adhere well during induction.
Given those caveats, Vernon says he thinks the new regimen is ready for a workout. "I’m encouraging programs to treat well-qualified patients with this regimen and to follow them carefully, so we can begin to acquire some real-world data."
Reaction to findings mixed
When the CDC’s analysis of trial data was presented at last month’s American Thoracic Society conference in Toronto, reactions ranged from cautious to enthusiastic. Some TB experts said they wanted to wait for more data; others declared they already are using the once-weekly regimen in selected patients.
Certainly, the trial data show the CDC consortium is a valuable new player on the scene, says Neil Schluger, MD, newly elected chair of the TB Trials Consortium’s steering committee and pulmonologist at Columbia Presbyterian Medical Center’s New York-Columbia Hospital in New York City. "This is the first Phase III trial of anti-TB drugs done in a very long time," Schluger says. "It shows this consortium can do high-quality research."
When DTBE experts first began to look at the data, it seemed there were five factors, not just two, that predicted either treatment failure or relapse, says Vernon: cavitation on X-ray, bilateral disease, culture positivity at two months, white race, and being more than 10% underweight.
Later, analysts decided just two — cavitation and culture-positivity at two months — were strong predictors of relapse or failure. Even though it excludes more patients, the best factor to use is probably cavitation, not culture positivity, Vernon says.
In the trial, only about 45% of patients were negative for cavitation; about 80%, by comparison, were sputum-culture negative by two months. But when analysts used cavitation as the cut-off point, the rate of unfavorable events was 2.9% with rifapentine and 2.5% with standard therapy, he says. With culture positivity used as the cut-off point, the rate of unfavorable events rose to 6% with rifapentine vs. 4% with standard therapy.
"Nobody wants a bunch of patients who are relapsing," Vernon says. "Even though using cavitation [as the cut-off point] gives you a slightly smaller group of eligible patients, treatment results are better. I think clinicians will accept a difference of 2.9% vs. 2.5%, but not a 6% vs. 4% difference."
There’s another reason to use cavitation. "It takes you six weeks, maybe two months, to get back results on a culture," he points out. "By then you’re at four months. Now what? You know you’re going to have to switch back to twice-weekly therapy, but for how long?"
Programs that disqualify everyone with cavitation still will save money with the once-weekly regimen, compared with standard therapy, even after adding in costs associated with the slight increase in problems using rifapentine, according to a DTBE model presented in Toronto, says Vernon.
In the end, of course, clinicians and programs must weigh pluses and minuses and make up their own minds, he concedes. Patients, too, should be fully informed about their choices, he adds.
Perhaps most exciting is the prospect of having higher dose levels of the drug available. Most TB experts, Vernon included, say they’re confident that problems associated with the 600 mg level will disappear when the dose is increased to 900 mg or 1,200 mg.
A year ago, testing for tolerability and safety was begun in humans at the 900 mg level. If researchers decide that level is well-tolerated, a second group will be started on 1,200 mg.
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