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The Relationship of 6-Mercaptopurine Medication Adherence to Clinical Outcomes in Pediatric Cancer

Rohan, Jennifer M
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1416570460

Abstract Details

2015, PhD, University of Cincinnati, Arts and Sciences: Psychology.
Objective. To investigate a multidimensional framework for investigating oral 6-mercaptopurine (6MP) medication adherence using indirect (i.e., behavioral: electronic monitoring) and direct measures (i.e., pharmacological: metabolites) of adherence to predict clinical outcomes over time in a multisite cohort of pediatric patients diagnosed with ALL or LBL. Methods. Adherence to 6MP and its relationship to clinical outcomes were examined for 139 patients ages 7-19 years diagnosed with ALL or LBL across six centers. Medication adherence was measured using two objective methods: behavioral adherence (i.e., electronic monitoring of 6MP) and pharmacological adherence (i.e., metabolite profiles of 6MP). Behavioral measures of adherence were collected daily and downloaded at three-month intervals. Pharmacological measures of adherence were obtained at three-month intervals via serum assay. Health outcomes were measured at quarterly intervals through medical chart reviews. Results. Unconditional growth curve modeling indicated that the mean percentage of behavioral adherence was 84.4% at baseline and declined over 15 months of follow-up to 75.2%. Three trajectories of 6MP behavioral adherence were identified: 1) optimal adherence (67.1% of patients): averaging 95% behavioral adherence across 15 months of follow-up; 2) moderate adherence (20%): relatively stable poor adherence (67%); and, 3) chronically nonadherent (12.9%): behavioral adherence decreased from 62.7% to 30%. Three metabolite profiles were identified: high levels of one metabolite and low levels of the second metabolite were considered adherent: 1) high TGN-low MMP (18.9%); and, 2) low TGN-high MMP (46.2%). Low levels of both metabolites were considered nonadherent: low TGN-low MMP (34.9%). Patients presenting with the nonadherent metabolite profile (low TGN-low MMP) had the lowest adherence rates over time (70% to 76%) relative to those presenting with adherent metabolite profiles (85 to 90%). With respect to patterns of medication adherence and relationship to clinically-relevant health outcomes, there were no significant differences observed between patients in the adherent versus nonadherent behavioral adherence trajectories with respect to mean absolute neutrophil counts (ANC), risk for infection as measured by ANC, healthcare utilization, or risk for relapse. On the other hand, there were significant differences observed among the three metabolite profiles and clinically-relevant health outcomes. Those patients in the low TGN-low MMP metabolite group had higher ANCs, had a decreased risk for infection, and were at a higher risk for relapse relative to the adherent metabolite profiles. There were no differences observed among the three metabolite clusters with respect to healthcare utilization. Conclusions. This study provided the first example of how behavioral adherence can be mapped on to pharmacological measures of medication adherence in a study of pediatric cancer. Although behavioral patterns of medication adherence deteriorated over time, pharmacological measures of medication adherence indicated relatively stable patterns of medication adherence across the 15 month period. Medication adherence predicted ANC and relapse rates. Adherence promotion interventions might be tailored to subgroups of patients who demonstrated problematic patterns of treatment adherence that could place them at risk for relapse. In addition, patients who demonstrate adequate levels of medication adherence could benefit from less intensive, preventative interventions to sustain and improve their adherence over time.
Dennis Drotar, Ph.D. (Committee Chair)
Alexander Vinks, Pharm.D. Ph.D. (Committee Member)
Steven Howe, Ph.D. (Committee Member)
Farrah Jacquez, Ph.D. (Committee Member)
93 p.
Psychology
adherence; pharmacology; pediatrics; cancer; statistical methodology; leukemia

Recommended Citations

Citations

  • Rohan, J. M. (2015). The Relationship of 6-Mercaptopurine Medication Adherence to Clinical Outcomes in Pediatric Cancer [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1416570460

    APA Style (7th edition)

  • Rohan, Jennifer. The Relationship of 6-Mercaptopurine Medication Adherence to Clinical Outcomes in Pediatric Cancer. 2015. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1416570460.

    MLA Style (8th edition)

  • Rohan, Jennifer. "The Relationship of 6-Mercaptopurine Medication Adherence to Clinical Outcomes in Pediatric Cancer." Doctoral dissertation, University of Cincinnati, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1416570460

    Chicago Manual of Style (17th edition)

ucin1416570460
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© 2015, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.