development of an objective methodology to measure medication adherence to oral thiopurines in paediatric patients with acute lymphoblastic leukaemia—an exploratory study

• Published in: European journal of clinical pharmacology 2009-11, Vol.65 (11), p.1105-1112
• Main Authors: Hawwa, Ahmed F, Millership, Jeff S, Collier, Paul S, McCarthy, Anthony, Dempsey, Sid, Cairns, Carole, McElnay, James C
• Format: Article
• Language: English
• Subjects: Adolescent; Antimetabolites, Antineoplastic - therapeutic use; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Child; Child, Preschool; Compliance; Drug therapy; Female; Hematologic and hematopoietic diseases; Humans; Leukemia; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Male; Medical sciences; Medication Adherence; Mercaptopurine - blood; Mercaptopurine - metabolism; Mercaptopurine - therapeutic use; Parents; Parents & parenting; Pediatrics; Pharmacokinetics and Disposition; Pharmacology. Drug treatments; Pharmacology/Toxicology; Precursor Cell Lymphoblastic Leukemia-Lymphoma - drug therapy; Questionnaires; Thioguanine - blood; Uric Acid - analogs & derivatives; Uric Acid - blood
• ISSN: 0031-6970; 1432-1041
• DOI: 10.1007/s00228-009-0700-1

Aims To develop a method that prospectively assesses adherence rates in paediatric patients with acute lymphoblastic leukaemia (ALL) who are receiving the oral thiopurine treatment 6-mercaptopurine (6-MP). Methods A total of 19 paediatric patients with ALL who were receiving 6-MP therapy were enrolled in this study. A new objective tool (hierarchical cluster analysis of drug metabolite concentrations) was explored as a novel approach to assess non-adherence to oral thiopurines, in combination with other objective measures (the pattern of variability in 6-thioguanine nucleotide erythrocyte concentrations and 6-thiouric acid plasma levels) and the subjective measure of self-reported adherence questionnaire. Results Parents of five ALL patients (26.3%) reported at least one aspect of non-adherence, with the majority (80%) citing “carelessness at times about taking medication” as the primary reason for non-adherence followed by “forgetting to take the medication” (60%). Of these patients, three (15.8%) were considered non-adherent to medication according to the self-reported adherence questionnaire (scored ≥ 2). Four ALL patients (21.1%) had metabolite profiles indicative of non-adherence (persistently low levels of metabolites and/or metabolite levels clustered variably with time). Out of these four patients, two (50%) admitted non-adherence to therapy. Overall, when both methods were combined, five patients (26.3%) were considered non-adherent to medication, with higher age representing a risk factor for non-adherence (P