TAKE-IT Intervention Improves Medication Adherence in Children and Young Adults

Pediatric kidney transplant recipients face a high-risk period during adolescence and young adulthood. Rates of graft failure increase from approximately 11 years of age and are higher in patients between 17 and 24 years of age than in any other age group. One factor contributing to the high graft failure rates in this age group may be poor adherence to immunosuppressive therapy, which is a key factor limiting survival of renal allografts in any age group.

Most poor adherence is unintentional; forgetting and poor organization and planning were the barriers to adherence most often cited by young kidney transplant recipients. The ability to manage medications may also be affected by neurocognitive dysfunction, particularly disturbances in executive function and memory associated with pediatric chronic kidney disease.

In 2008, the National Institutes of Health called for randomized trials promoting interventions for adolescent and young adult kidney transplant recipients. The TAKE-IT (Teen Adherence in Kidney Transplant Effectiveness of Intervention Trial) intervention was developed to address modifiable barriers to adherence in that patient population. The intervention utilized an approach that was individually tailored  and included a combination of electronic monitoring and feedback, problem-solving skills, goal setting, and adherence support using text message dose reminders. The intervention showed promise in prior studies and has been reinforced with systematic reviews.

Bethany J. Foster, MD, and colleagues recently conducted a prospective, unblinded parallel-arm randomized trial to examine the efficacy of a novel multicomponent adherence-promoting intervention, compared with an attention control condition, in improving medication adherence in adolescent and young adult kidney transplant recipients. The researchers sought to test the hypothesis that adherence would be significantly better with the TAKE-IT intervention compared with a control group. Results were reported in the American Journal of Kidney Diseases [2018;72(1):30-41].

The intervention in TAKE-IT was designed to improve implementation of the prescribed medication regimen, defined as “the extent to which a patient’s actual dosing corresponds to the prescribed dosing regimen.” The trial was conducted at eight pediatric transplant centers in Canada and the United States from February 2012 to May 2016.

The study population included prevalent kidney-only transplant recipients 11 to 24 years of age who were ≥3 months post-transplant; expected follow-up was 15 months. Exclusion criteria were impending graft failure, severe neurocognitive disabilities, lack of electronic pillbox connectivity, use of liquid immunosuppressive medications, having a sibling participating in another adherence-promoting intervention study, or the inability to communicate comfortably in English (or French, Montreal site only).

During a 3-month run-up period, adherence was electronically monitored in all participants; the run-up period was followed by a 12-month intervention. Participants in the TAKE-IT arm could opt to receive text message, e-mail, and/or visual cue dose reminders; they also met with a coach at 3-month intervals to review adherence data from the previous 3 months. Barriers identified as important by the participant were addressed using “Action-Focused Problem Solving” techniques. Participants in the control group met with coaches at 3-month intervals but did not receive feedback on adherence data.

The primary outcomes of interest were electronically measured “taking” adherence, defined as the proportion of prescribed doses of immunosuppressive medications taken), and “timing” adherence, defined as the proportion of doses of immunosuppression medication taken between 1 hour before and 2 hours after the prescribed time of administration, on each day of observation. Secondary outcomes included the standard deviation of tacrolimus trough concentrations, self-reported adherence, acute rejection, and graft failure.

Of the 388 patients screened, 277 met eligibility criteria. Of those, 172 were enrolled between February 3, 2012, and February 1, 2015. The final cohort included 169 participants, 81 in the intervention arm and 88 in the control arm. The two groups were similar in baseline characteristics, although not perfectly balanced. Median age in the intervention arm was 15.5 years and 57% were male; in the control arm, median age was 15.8 years and 61% were male.

Preintervention results of the adolescent and parent versions of the Medication Barriers Survey were similar between the two groups as well. Compared with controls, patients in the intervention arm spent more time with the coach.

In the intervention group, taking adherence improved immediately after the first intervention visit and remained fairly stable thereafter, compared with the control group where there was no change in taking adherence. During the intervention period, taking adherence was 100% in 78% of days for the intervention arm and 68% for the control arm. Among patients in the intervention arm, the likelihood of better taking adherence was significantly greater than in the control arm (odds ratio [OR], 1.66; 95% confidence interval [CI], 1.15-2.39; P=.006).

Immediately following the first intervention visit, timing adherence also improved in the intervention group. Timing adherence was 100% on 73% of days in the intervention arm and 100% on 61% of days in the control arm. The odds of higher timing adherence scores were significantly higher in the intervention arm compared with the control arm (OR, 1.74; 95% CI, 1.21-2.50; P=.003). In reweighted analyses and after supplementing electronic adherence data with patients’ adherence logs and adjusting for confounders, the results were unchanged.

In analyses of secondary outcomes, there was no difference between the two groups in the standard deviation of tacrolimus trough concentrations. Taking and timing adherence were both high on self-report and did not differ between the groups. There were no graft failures in the overall cohort. There was a nonstatistically significant difference between the groups in acute rejection rates; the rates were numerically lower in the intervention group than in the control group.

There was no difference in annualized change in estimated glomerular filtration rate during the intervention interval by group. With the exception of cytomegalorvirus infection that was higher in the intervention group, there were no differences in rates of adverse events between the groups.

Limitations cited by the authors included the possibility of attention bias due to the longer duration of visits for intervention patients compared with controls, the inability to power the study to access the outcomes of numbers of graft failures and acute rejections, and the possibility that the findings may not be generalizable due to the relatively small proportion of participants who were black (13% in the control arm and 11% in the intervention arm).

In conclusion, the researchers said, “The multicomponent TAKE-IT intervention resulted in significantly better medication adherence than the control condition. Better medication adherence may result in improved graft outcomes, but this will need to be demonstrated in larger studies.”

Takeaway Points

  1. Premature graft loss in child and young adult kidney transplant recipients is due, in part, to poor adherence to immunosuppressive medication regimens. The Teen Adherence in Kidney Transplant Effectiveness of Intervention Trial (TAKE-IT) tested the hypothesis that participants assigned to the TAKE-IT intervention would have better medication adherence than those in a control group.
  2. The TAKE-IT intervention was designed to address common modifiable barriers to adherence with an approach that included a combination of monitoring and feedback, training in problem-solving skills, and technology-based adherence support.
  3. Participants in the intervention arm had significantly better adherence to medication compared to those in the control arm.