Children with liver transplants often don't stick to their meds

Last Updated: 2018-01-05

By Scott Baltic

NEW YORK (Reuters Health) - Children with liver transplants who initially adhere to their prescribed immunosuppressive medications do not necessarily remain adherent in the second year after transplant, and those with higher rates of nonadherence more often face late acute rejection, researchers report.

"Our results suggest that good baseline adherence does not guarantee adherence later on, that nonadherence is likely to persist in the absence of interventions, and that monitoring of adherence and interventions to improve it should be expected to last for years if transplant outcomes are to be improved," write the study authors, led by Dr. Eyal Shemesh of the Department of Pediatrics and Kravis Children's Hospital at the Icahn School of Medicine at Mount Sinai in New York City.

He and his colleagues analyzed prospective data from 400 children (ages 1 to 17 years) enrolled in the MALT (Medication Adherence in Children Who Had a Liver Transplant) trial, conducted at five U.S. pediatric liver transplant centers.

Medication nonadherence is associated with most cases of late acute rejection (LAR) in pediatric liver transplant recipients, the report notes.

The study tracked adherence using the Medication Level Variability Index (MLVI), which measures blood levels of tacrolimus, the primary immunosuppressant used to prevent rejection in liver transplant recipients. Measurements are generally obtained once every three months.

Of 294 MALT participants with MLVI data reported, 222 had an MLVI of 2.0 or less (indicating greater medication adherence) in year 1, and 72 had a first-year MLVI >2.0 (suggesting nonadherence), according to the December 4 online report in Liver Transplantation.

Of the 222 initially adherent patients, 41 (18.5%) became nonadherent in year 2. Of the 72 initially nonadherent patients, 43 (59.7%) remained nonadherent in the second year.

Patients determined to be adherent in both year 1 and year 2 had an LAR rate of only 4.4%. However, the LAR rate was 22.9% for patients with MLVI values indicating nonadharence during either year of follow-up, and it was 34.9% for patients who were nonadherent during both years.

Children from single-parent households and of lower socioeconomic status generally had worse adherence. Patients who had private health insurance tended to have stable adherence, while those with other (mostly public) health insurance had worsening adherence over time, although the authors caution that differing patient risk profiles between the insurance pools, rather than insurance itself, might explain that finding.

Overall, adolescents (ages 13 to 17) were no less consistent in adherence than younger children.

The authors note that in the absence of interventions, initial nonadherence to immunosuppressive drugs at any point is likely to persist. They conclude that "regular monitoring of adherence should be considered for all patients, including those who appear to be managing their medications well at baseline" and that "nonadherence should be addressed as soon as it is identified."

"This is the first study that looked at nonadherence post-transplant prospectively and over a long period of time. (It) is also the first study in transplant medicine to prospectively use a biomarker of adherence (MLVI) to look at adherence over time," Dr. Shemesh told Reuters Health by email.

Regarding which interventions are likeliest to improve medication adherence, he said, "I wish I knew."

A recent systematic review of such interventions in transplant recipients found that almost all of them "try to 'intervene' with everyone - for example, educate all adolescents about the importance of taking the meds," Dr. Shemesh said, adding that many patients who take their medications therefore receive an intervention they don't need, which is not cost-effective.

He also explained that patients who are nonadherent - and therefore don't do well - don't even agree to participate in most studies, creating a substantial selection bias.

To intervene effectively, Dr. Shemesh said, only patients who don't take their medications regularly should be targeted for interventions, but that requires a robust monitoring method, such as a biomarker.

"So monitor continuously, and when monitoring suggests that there is a problem, intervene immediately, and intensively, perhaps with the help of the family. . . . It's not just reminders that are needed, but an actual clinician to evaluate what is going on in each case," he concluded.

The study had no industry funding.

SOURCE: http://bit.ly/2BGTXez

Liver Transpl 2017.