Proteus Digital Health’s ingestible pill and sensor system could improve medication adherence, and subsequently treatment, for patients with tuberculosis (TB), according to new data from an independent study conducted in California.
Published Friday in PLoS Medicine, the trial found Proteus’ system to accurately determine whether or not a medication was taken. Patients using the system at home were more likely to keep up with their doses, and across the board preferred the system to gold-standard adherence programs requiring medication to be confirmed by an in-person provider.
This comparison of [wirelessly observed therapy (WOT)] and [directly observed therapy (DOT)] has policy implications for TB treatment within the US,” the study’s authors, who hailed from the University of California, San Diego, Stanford University, HHS and Orange County Health Care Agency, wrote. “If recommendations for TB treatment require DOT dosing, based on our results, a WOT dose can be considered equivalent to a DOT dose. Our findings provide rigorous data supporting WOT accuracy in clinical and home settings during the continuation phase of TB treatment.”
When comparing the WOT accuracy system’s accuracy under supervision, the researchers reported 99.3% rate of positive detection accuracy (95% CI, 98.1% to 100%) among 77 TB patients.
In the second part of the trial randomly assigning WOT or DOT to 61 patients, the system indicated a 93% rate of daily dosage adherence compared to a 63% rate observed among those confirming their adherence in person (p < .001). An additional analysis removing weekends and public holidays as well as held doses of the medication also found WOT and DOT adherence rates to be similar (95.6% versus 92.7%; p = .03), and concluded that the former was non-inferior “at a very conservative non-inferiority margin of 2%.”
There was no significant difference in adverse event rates between the two study arms, with those occurring in the WOT arm often related to the patch’s placement on the skin. All participants said that they would prefer to use the ingestible system before being randomized to the second phase of the trial, and the public health department requested that all patients be permitted to continue using the system until the completion of their TB treatment.
HOW IT WAS DONE
The researchers recruited adult TB patients taking isoniazid plus rifampin with no evidence of drug-resistant TB from two public health treatment programs in Southern California, which also served as the study sites. These patients were an average of 43 years of age, and largely white (39%) or Asian (42%) with frequent reported Hispanic ethnicity (49%). A quarter had no high school diploma, and 58% reported being unemployed or disabled.
The study’s first phase had all patients receive a dose of their medication under direct supervision, while wearing the WOT system. This analysis collected a total of 1,073 person days of data, excluding only days in which a dose was not administered or days in which the WOT was not applied correctly.
The second phase examined many of these same patients, but randomly assigned them 2:1 to continue their treatment using the WOT system or five-days-a-week DOT. Those using the Proteus system were required to change the monitoring patch each week on their own, and could view a log of their progress on their smartphone. Study staff used Proteus’ website to check patients’ adherence each weekday, and texted or called patients if the dose was not confirmed by the system. Both arms were set to last 16 weeks, although those using WOT were permitted to finish their treatments. This yielded a total of 5,926 days of observation data for analysis (4,022 days for the WOT arm, 1,904 days for the DOT arm).
TB kills more people each year than any other infectious disease, and as an opportunistic infection is especially deadly to those with weakened immune systems. Recent years have also seen a troubling rise in antibiotic-resistant strains of the disease, driven largely by inconsistent adherence to medication regimens that can last several months.
Clamping down on missed doses would greatly reduce the disease’s resurgence in treated patients, as well as reduce its spread in high-burden regions.
"We are now moving into an era of all-oral regimens for the treatment of drug-resistant TB, without the need for daily injections. And we now have an opportunity to explore the potential of medication adherence support using [wirelessly observed therapy (WOT)] in the use of TB treatment regimes worldwide," Dr. Constance Benson, a professor of medicine at UCSD and co-lead on the trial, said in a statement. "We have a limited number of drugs available for the drug-resistant strains of TB and better treatment support will be essential to help ensure that the integrity of those drugs is preserved in the long term.”
Proteus, meanwhile, had its first patch cleared in 2010 and its first pill cleared in 2012. But it made headlines last November when the FDA approved Abilify MyCite, which allowed the digital ingestion tracking system to be combined with a therapeutic. Before, clinicians had to take the pill and add the Proteus chip, whereas this system more closely integrated the sensor and pill.
Proteus and Otsuka Pharmaceutical would go on to strike a five-year, $88 million deal in late 2018, but outside of a couple provider and university partnerships the company has generally laid low in the year since.
“Our research demonstrates WOT is a self-management system that can provide near-real–time actionable information, allowing patient-centered care to support adherence,” the researchers wrote. “The findings of this study suggest that WOT technology offers advantages over DOT for adherence confirmation and support, and that WOT should be incorporated into implementation trials of oral MDR regimens in global settings.”