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Self-administered therapy noninferior to direct observation for latent TB
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Patients in the United States who self-administered once-weekly isoniazid and rifapentine to treat latent tuberculosis infection had a high rate of treatment completion, demonstrating noninferiority to direct observation, according to phase 4 study data.
“Cost-effectiveness modeling found that self-administered, once-weekly [isoniazid] and rifapentine had an advantage over other regimens if adherence remained high and toxicity did not increase,” Robert Belknap, MD, an assistant professor of medicine in the division of infectious diseases at the University of Colorado Denver, and colleagues wrote in Annals of Internal Medicine. “However, adherence to the once-weekly regimen in the [self-administered therapy] groups was unknown, and the frequency and severity of adverse events in patients monitored at monthly visits rather than weekly during [directly observed therapy] had not been evaluated.”
Researchers conducted a phase 4 randomized clinical trial comparing self-administration of once-weekly isoniazid and rifapentine with direct observation therapy, both in terms of treatment completion — defined as 11 or more doses within 16 weeks — and safety. They enrolled 1,002 adults aged 18 years and older with latent TB infection from outpatient TB clinics in the U.S., Spain, Hong Kong and South Africa. Participants were randomly assigned to receive treatment either by direct observation, self-administration with monthly monitoring, or self-administration with weekly text message reminders and monthly monitoring.
Their analysis showed that self-administered treatment without reminders was noninferior to direct observation in the U.S.; however, other comparisons did not meet noninferiority criteria. Treatment completion was 87.2% (95% CI, 83.1-90.5) for patients in the direct observation group, 74% (95% CI, 68.9-78.6) for patients who self-administered therapy and 76.4% (95% CI, 71.3-80.8) for patients who self-administered therapy and received weekly text message reminders. For U.S. patients, completion of once-weekly isoniazid and rifapentine treatment was 85.4% (95% CI, 80.4-89.4), 77.9% (95% CI, 72.7-82.6), and 76.7% (95% CI, 70.9-81.7), respectively.
Text message reminders did not impact treatment completion in the U.S., but more patients who self-administered the drugs and received reminders completed therapy compared with those who self-administered without reminders in Spain, Hong Kong and South Africa.
The researchers said only a few drug-related adverse events occurred and rates were similar across groups.
In a related editorial, Haileyesus Getahun, MD, coordinator of the TB/HIV and community engagement unit at the WHO Global TB Programme, and Alberto Matteelli, MD, a lecturer at the University of Brescia in Italy, wrote that these findings show that promoting self-administered treatment of latent TB infection may be beneficial in some settings. However, patient-related factors, along with health system and broad socioeconomic barriers, must be addressed to ensure adherence, they wrote.
“A platform of shared decision-making between patients and providers will be essential in identifying circumstances in which self-administration is likely to be successful,” Getahun and Matteelli wrote. “Evidence-based incentives and approaches tailored to the specific needs of patients and their families need to be promoted as part of programmatic management of [latent TB infection].” – by Savannah Demko
- References:
- Belknap R, et al. Ann Intern Med. 2017;doi:10.7326/M17-1150.
- Gethun H, Matteelli A. Ann Intern Med. 2017;doi:10.7326/M17-2639.
Disclosures: Belknap reports grants from the CDC. Please see the full study for a complete list of all other authors’ relevant financial disclosures. Getahun and Matteelli report no relevant financial disclosures.
Perspective
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Karen Jacobson, MD MPH
This study supports that in the U.S., self-administered, once-weekly isoniazid with rifapentine was tolerated without added toxicity compared with directly observed administration. Additionally, treatment completion of the 12-week regimen was noninferior in the self-administered group compared with the directly observed therapy group, although the completion rate was lower in the self-administered group.
The study supports opening up this shorter latent TB infection regimen to patients in a self-administered fashion with monthly follow ups, which is a much more patient-centric way to give treatment, allowing autonomy and more flexibility. The caveat is that patients lose the weekly human support of ensuring treatment is taken, and completion was lower in the self-administered group and may fall even lower outside of trial settings.
Providers can feel more confident in having the option, especially with fewer toxicity concerns, and determine that the patient is a good candidate for completing treatment without regular weekly observation. Having the option to remove directly observed therapy may make this regimen feasible for many more patients. Interestingly, the outcomes were much worse in South Africa, raising questions of its generalizability to all settings globally.
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