Adherence to Azathioprine/6-Mercaptopurine in Children and Adolescents with Inflammatory Bowel Diseases: A Multimethod Study

Abstract

Background. Measurement of the degree of adherence is a key element for the evaluation of treatment efficacy and safety; thus, adherence plays an important role in clinical research and practice. The aim of this study was to investigate medication adherence in children with inflammatory bowel disease (IBD) utilizing a multimethod assessment approach. A further aim was to examine factors that can influence adherence within this population. Methods. Medication adherence in 47 children (age range 3 to 17 years) with IBD in three centers in Northern Ireland and Jordan was assessed via subjective (parent and child versions of the Medication Adherence Report Scale (MARS) specific questionnaire) and objective methods, that is, high-performance liquid chromatography (HPLC) determination of the 6-mercaptopurine (6-MP) and azathioprine (AZA) metabolites in packed red blood cell samples taken during a clinic visit. Beliefs about prescribed medicines were also assessed in parents/guardians using the Beliefs about Medicines Questionnaire (BMQ). Results. An overall nonadherence to AZA/6-MP therapy in children with IBD was found to be 36.17% (17 out of 47 patients were classified as nonadherent using at least one of the assessment methods). A total of 41 patients (91.1%) were classified as adherent to AZA or 6-MP using the blood sampling, while adherence rates using the MARS questionnaire completed by children and parents/guardians were 60.6% and 72.7%, respectively. The latter provides a more longitudinal measure of adherence. Child self-reported nonadherence rates were significantly higher than parent/guardian reported rates (p=0.013). Binary logistic regression analysis identified age to be independently predictive of adherence, with adolescents (children aged ≥ 13 years old) more likely to be classified as nonadherent. Regarding the BMQ, when parental/guardian necessity beliefs outweighed concerns, that is, higher scores in the necessity-concern differential (NCD), adolescents were more likely to be classified as adherent. Conclusion. Results provide evidence for ongoing adherence challenges in the paediatric population with IBD. It is recommended that parents/guardians (particularly of older children) and older children themselves, should receive enhanced counselling and education about their prescribed medicines.

Prevalence and predictors of medication non-adherence in children with inflammatory bowel disease in China: A cross-sectional study

“…To our surprise, parent reported non-adherence (31.37%) was higher than Child self-reported non-adherence (25.00%) in this study, however, the difference being not statistically significant. This was different from the findings of ( Alsous et al, 2020 ), ( Reed-Knight et al, 2011 ), but ( Ingerski et al, 2010 ). Furthermore, it revealed that children reported lower scores for unintentional non-adherence and tended to have higher scores for intentional non-adherence, compared with parent-reported results, but the differences between them were not statistically significant.…”

“…This is the first study to investigate medication adherence and analyze the predictors of non-adherence to medication in Chinese children with IBD. Our results showed that about a quarter of children with IBD have poor medication adherence, which is higher than the rate in the United States (14.61%–17.47%) ( Greenley et al, 2015 ), but similar to that in South Korea (31.2%) ( Lim et al, 2020 ), lower than that in Jordan and the United Kingdom (36.2%) ( Alsous et al, 2020 ), and much lower than that in Japan (43.0%) ( Tanaka et al, 2021 ). Non-adherence to medication in children with IBD is common worldwide.…”

Usefulness of Measuring Thiopurine Metabolites in Children with Inflammatory Bowel Disease and Autoimmunological Hepatitis, Treated with Azathioprine

“…In that group, there were five CD and two UC patients. We did not asses the adherence to treatment, using any specific questionnaires, although a multimethod assessment is more widely used [ 3 ]. In the future, we plan to assess adherence not only by objective methods but also with a specific questionnaire for both: parents and children.…”

“…Hommel et al, evaluating adherence in 42 IBD adolescents, found that the majority of the sample (93%) had demonstrated quantifiable 6-TGN levels but only 14% were within the therapeutic range what indicated that nonadherence assessment was especially important in the group of adolescents, faced with learning to manage a chronic condition and negotiate normal developmental issues [ 16 ]. Alsous et al [ 3 ], using a binary logistic regression analysis, identified the age to be independently predictive of adherence, with adolescents more likely to be classified as nonadherent. The mean age of our nonadherent subjects was 15 years.…”

“…AZA and 6-MP are immunosuppressants with short half-lives (3 and 1.5 hours, respectively) and, therefore, measuring their metabolites is a more appropriate method, both for adherence assessment and therapeutic drug monitoring. An intracellular accumulation of AZA/6-MP metabolites occurs over a period of 2–3 weeks [ 3 ]. Various studies have examined the relationship between 6-TGN levels in red blood cells and a clinical response to thiopurine therapy.…”