TOPLINE

A remote behavioral intervention guided by the Medication Level Variability Index (MLVI), an electronic health record-derived marker based on routinely collected immunosuppressant blood levels, showed potential to lower the risk for rejection among adolescent and young adult recipients of liver transplant, although the results were not statistically significant.

METHODOLOGY

• Young recipients of liver transplants are particularly vulnerable to treatment failure from nonadherence to medication because they require lifelong immunosuppression, and the MLVI offers a practical tool to identify patients at a risk for nonadherence and, in turn, organ rejection.
• This primary analysis of a prospective trial conducted across 13 pediatric transplant centers in North America involved 148 adolescent and young adult recipients of liver transplant (mean age at enrolment, 15.5 years) with MLVI scores exceeding 2 units.
• Participants were randomly assigned to receive either a 2-year remote behavioral telemetric intervention (n = 72) or standard of care (SOC; n = 76). The intervention included video or audio calls among interventionists, patients, and parents, focusing on medication-taking practices and barriers to adherence; SOC addressed nonadherence per usual practice and could involve the use of the measured MLVI score to inform clinical care.
• MLVI scores were calculated as the SD of at least three consecutive tacrolimus blood levels from outpatient records over the 2 years before screening, with scores exceeding 2 units indicating a persistent behavior of nonadherence to medication; during the study, scores were recalculated quarterly using data on blood levels from the preceding 12 months.
• The predefined primary endpoint was the incidence of biopsy-confirmed acute cellular rejection, adjudicated by three expert pathologists; secondary outcomes were changes in serum alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) levels and MLVI scores.

TAKEAWAY

• The incidence of the primary endpoint was lower in the intervention group than in the SOC group (8.3% vs 15.8%), but the difference did not reach statistical significance (P = .20).
• Patients in the intervention vs SOC group had lower mean maximal ALT (86.6 IU/L vs 110.5 IU/L) and GGT (142.7 IU/L vs 165.5 IU/L) levels; fewer patients in the intervention vs SOC group had ALT levels > 150 IU/L (13.9% vs 23.7%).
• Rejections in the SOC group occurred throughout the eight quarters and were associated with MLVI scores > 2, whereas the intervention group had most rejections during the first two quarters. The mean MLVI score was comparable at the end of the study, despite a faster rate of reduction in the score in the intervention group than in the SOC group.
• No deaths or cases of posttransplant lymphoproliferative disorders, new-onset diabetes requiring insulin, new-onset systemic hypertension requiring medication, or serum creatinine levels > 176.8 μmol/L were observed. Two patients in the SOC group and one in the intervention group underwent retransplantation after an earlier rejection.

IN PRACTICE

“[The] MLVI score emerges as a useful marker of clinically significant nonadherent behavior, which increases rejection risk in transplant recipients. The same concept (albeit with different thresholds) could be applied in other circumstances in which serial ambulatory medication blood levels are obtained and even more broadly whenever an objective outcome metric that is closely tied to adherence to medical recommendations (such as blood pressure) is obtained repeatedly,” the authors of the study wrote.

SOURCE

The study was led by Eyal Shemesh, MD, Icahn School of Medicine at Mount Sinai, New York City. It was published online in the American Journal of Transplantation.

LIMITATIONS

The trial was single-blinded. As patients and clinicians were aware of nonadherence concerns, efforts to improve patients’ medication-taking behavior may have occurred outside the study intervention. The intervention may not have been sufficiently comprehensive to affect outcomes.

DISCLOSURES

The study was funded by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health. The authors declared having no conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.