Guidelines roll out two new variations
Experts give both a thumbs up
New TB treatment guidelines expected out this fall will offer providers and patients alike more choices. They also will give TB patients a better shot at being cured, experts say.
"What these new guidelines are saying is that all TB patients are not alike, and that TB treatment isn’t just a cut-and-paste affair," says Lee Reichman, MD, MPH, director of the National Tuberculosis Center at the New Jersey Medical School in Newark. "You’ve got to think about what you’re doing and look at how the individual patients responds."
With the publication of the new guide by the Centers for Disease Control and Prevention, American Thoracic Society, and the Infectious Disease Society of America, two new treatment variations now have the experts’ official blessing.
For the 40% of so of TB patients who are HIV-negative and have noncavitary disease, the continuation phase of treatment can now consist of a once-weekly regimen of rifapentine and isoniazid. The rifapentine option gets a B-1 rating — meaning that it’s an "acceptable alternative" to the conventional regimen, and that it gets its approval based on evidence from a randomized controlled trial.
For the 10%-20% of TB patients who do have cavitary disease and whose cultures also turn out to have been positive at two months, the new guidelines counsel an additional three months of treatment.
The new guidelines also will emphasize the role of the provider in making sure the patient is cured and will stress the importance of using "patient-centered" therapy with direct observation forming an important component.
Both additions are drawing applause from the ranks of clinicians. The once-weekly rifapentine option "should definitely be an asset," says Edward Nardell, MD, chief of pulmonary medicine at Cambridge (MA) Hospital. "It takes half the resources, and patients will love just coming to clinic once a week."
Everyone likes once a week
TB controllers in Denver, who have been using the once-weekly option since the trial testing began, say they’re extremely pleased. "Providers and patients both like it a lot," says Bill Burman, MD, infectious disease specialist at Denver Medical Health Center. Burman, who also is chairman of the Core Sciences Group of the federally funded TB Trials Consortium (TBTC), took part in the trial that assayed the efficacy of the new rifapentine option.
The other new piece of the guidelines — the three extra months for those who still are culture-positive at two months — isn’t altogether new, and has already been the preferred route for many providers. John Sbarbaro, MD, professor of medicine at the University of Colorado Health Sciences Center in Denver, says he’s been pushing extended treatment for years. "Whenever people ask me what to do about these patients, I always say to go longer. I mean, what do you have to lose but a little time?"
That doesn’t mean everyone’s been doing it. "We weren’t, until we started seeing the results from Study 22," Burman says, referring to the surprisingly strong evidence about relapse that popped up in the TBTC trial. "Even then, we were a little skeptical. So we went back and looked at our own data, and we found the exact same trend [toward relapse and failure] sitting right there under our noses."
No nasty surprises seen
No one seems worried about whether plugging in the new guidelines will lead to unanticipated toxicity. That was the unpleasant surprise that turned up as providers began to use the new two-month treatment for latent TB infection consisting of rifampin and pyrazinamide. Rifapentine’s safety profile has proven excellent among the 2,500-plus patients in whom it’s been tested, notes Burman, "with no suggestion that it’s anything other than very well tolerated if anything" he adds, "there have been fewer side effects than with rifampin."
As for the danger of relapse, only one clinician interviewed expressed any reservations. "I think we may be pushing right up to the limit with this once-weekly option, " says Philip Hopewell, professor of medicine at the University of California in San Francisco and associate dean of San Francisco General Hospital. "But I think this once-weekly option is probably right on the mark."
Burman responds that the trial data say it all. In the TBTC study, he points out, the rifapentine group relapsed at a rate of 2.7%, compared to 2.5% in the conventional-therapy group — a difference so slight it’s not statistically significant. (Details of the study findings should be out soon in an upcoming issue of Lancet.)
Once-weekly TB treatment has a respectable history, points out Sbarbaro. In a study carried out in Hong Kong decades ago, patients did well with once-weekly rifampin. In that study, rifampin was teamed with all four other anti-TB drugs, and patients gulped handfuls of pills once a week for nine months. "An interesting approach — you had to take a heck of a lot of pills, of course, but you only had to take em once a week," Sbarbaro notes.
What the future holds
For now, therapy for patients who do have cavitary TB will have to wait for once-weekly treatment until a closer match is found for rifapentine’s long half-life, says Rick O’Brien, MD, chief of the research and evaluation branch of the Division of TB Elimination at the Centers for Disease Control and Prevention (CDC) in Atlanta. A long-acting, "matrix" form of isoniazid actually would have done the trick — except that when CDC investigators looked more closely, they found the long-acting INH caused problems in patients who are so-called "rapid acetylators," O’Brien says. The antibiotic moxifloxacin, due to start TBTC trials soon, seems to offer the best hope; and preliminary work suggests moxi will indeed perform up to experts’ high expectations.
One day in the not-too-distant future, once-weekly therapy for treatment of latent TB infection (LTBI) may also win TB experts’ seal of approval. The TBTC’s Study 26 — which looks at a once-weekly regimen for LTBI — has already enrolled about 800 patients, O’Brien says.
The study will compare self-administered daily INH for nine months with once-weekly rifapentine teamed with INH. Because Study 26 aims to enroll a whopping 8,000 people with latent TB, TBTC investigators were initially nervous about how long the process would take. Fortunately, the consortium won some extra funding and has been able to add extra sites, both of which should facilitate the enrollment process.
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