This study is the first to examine both prevalence and frequency of medication nonadherence in pediatric IBD using a multimethod objective and subjective adherence assessment approach with behavioral and biological measures. Consistent with the primary hypothesis, results indicated that nonadherence prevalence was comparable to other adolescent chronic illness populations. In fact, prevalence of nonadherence was slightly higher for 5-ASA medications (i.e., 88%) using pill count data than has been observed in other adolescent populations. This suggests that this group of medications might be particularly difficult for adolescent patients to take regularly as prescribed. Factors that may make adherence to 5-ASA medications challenging include frequent dosing each day and quantity of pills per dose. Nonadherence frequency pill count data indicated that a considerable percentage of both 6-MP/azathioprine and 5-ASA doses are missed (38% and 49%, respectively). Thus, not only are a majority of IBD patients nonadherent (using < 80% as the cut point), but approximately 40% to 50% of medication doses are missed by patients.
Also consistent with our hypotheses, self-report adherence assessment data yielded considerably lower nonadherence (i.e., high adherence) estimates in this sample. While these data likely represent an overestimation of adherence, which is a common problem in adolescents, the comparison of objective and subjective data in this study highlights an important point: although adolescents demonstrate significant nonadherence to medication, they may not accurately perceive the extent of the problem. This discrepancy between subjective and objective adherence represents a salient opportunity and avenue for intervention by health care providers, and underscores the importance of multimethod adherence assessment.
Examination of bioassay data revealed a low percentage of patients with therapeutic 6-TGN levels, which was possibly a function of pharmacokinetic influence. Moreover, these assays did not accurately reflect objectively measured nonadherence. The exception to this was that patients with subtherapeutic/unquantifiable 6-TGN/6-MMPN levels exhibited extreme nonadherence prevalence and frequency. However, this finding is quite preliminary given the small subsample used. Importantly, perhaps the most significant finding of this study was that nonadherence to one medication was generalizable to the other medication. This was true for both objective and bioassay assessments in which patients that were nonadherent to 6-MP/azathioprine were also nonadherent to 5-ASA medications.
These findings have several clinical implications. Adherence should be monitored by patients, families, and practitioners and assessments should be incorporated into routine visits. Unfortunately, patients do not always bring medication to clinic visits for pill counts, leaving clinicians with restricted and less reliable options, such as self-reports or bioassays. The preliminary data from this study suggest that low metabolite values might indicate nonadherence to oral medication, and could potentially be used as a cursory screener for nonadherence. However, suspected nonadherence should always be verified by validated measures of adherence, and patient nonadherence should be normalized and discussed openly and nonjudgmentally with patients and their families. Ideally, an assessment of treatment adherence should include multiple measures to capitalize on the strengths of each and account for their inherent weaknesses. Although self-reported adherence is likely to be overestimated, it may serve as a catalyst to desensitize patients to discussing adherence issues during clinic appointments, and thus might improve the validity of future self-reporting. Finally, these data indicate that adherence to 5-ASA medications might be particularly challenging and should be considered as a target for intervention (e.g., modification of dosing schedule). Nevertheless, a thorough assessment of which treatments pose adherence difficulties and the specific barriers to completing those treatments is necessary for each patient as specific problem behaviors will vary considerably across patients.
The findings of this study should be considered within the context of several limitations. First, the modest sample size suggests that generalization of these findings should be made with caution. Second, the mean family income in this sample was higher than expected; however, the socioeconomic status of the IBD population is likely negatively skewed compared to other disease populations based on the overrepresentation of Caucasians diagnosed with IBD. Nevertheless, because nonadherence in this sample was similar to that found in other populations, it is unlikely that socioeconomic factors influenced the primary outcome variable in this study. Third, the adherence measures utilized in this study represent assessment tools that can readily be used in clinic or via follow-up telephone contact. Yet, more detailed information regarding patterns of nonadherence would likely have been available with the use of electronic monitoring of medication adherence. Finally, the extent to which metabolism of 6-MP/azathioprine was affected by liver functioning is not known as these tests were not conducted simultaneously with 6-TGN/6-MMPN assays.
Future research efforts focusing on large scale examination of nonadherence in this population is needed to establish generalizability and improve assessment methods; this is currently underway. Second, research should examine the value added contribution of adherence assessment via electronic monitors. The additional data from such an approach would inevitably result in further empirical questions regarding timing and patterns of dosing, and would be useful in developing treatment protocols and calculating optimal timing of such interventions. Additionally, longitudinal approaches to data analyses are needed to examine the predictive utility of various assessments for future adherence behavior. Moreover, statistical and pharmacokinetic modeling of adherence is warranted based on the novelty of this area of research. Finally, studies examining trajectories of adherence during patients’ transition from pediatric to adult health care are critical to understanding the changes in disease management behavior and potential points of intervention during this poorly understood developmental period for patients with IBD.