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Self-administered latent TB therapy noninferior to direct observation
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, from Denver Health and Hospital Authority and the University of Colorado Health Sciences Center, 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 to determine treatment completion, defined as 11 or more doses within 16 weeks, and safety of once-weekly isoniazid and rifapentine by self-administration compared with direct observation. 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 once-weekly isoniazid and rifapentine by direct observation, self-administration with monthly monitoring or self-administration with weekly text message reminders and monthly monitoring.
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, but 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 didn’t impact U.S. treatment completion in the U.S., but more patients completed therapy in the self-administered therapy with reminders group than those in the self-administered therapy alone group in Spain, Hong Kong and South Africa.
“Once-weekly [isoniazid] and rifapentine by [self-administered therapy] had high treatment completion in the United States, Spain, and Hong Kong,” Belknap and colleagues wrote. “This self-administered regimen with monthly monitoring may be an acceptable strategy for treating [latent TB infection] in the United States and could be considered in countries with similar approaches to TB prevention when [directly observed therapy] is not feasible.”
In a related editorial, Haileyesus Getahun, MD, from WHO Global TB Program, and Alberto Matteelli, MD, from 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
Disclosures: Belknap reports grants from the CDC. Please see the full study for a complete list of all other authors’ relevant financial disclosures. Getachun and Matteelli report no relevant financial disclosures.
Perspective
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The study supports opening up this shorter latent tuberculosis 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, which may fall even lower outside of trial settings.
Providers can feel more confident in having the option, especially lowering the toxicity concerns, but may still evaluate 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.