Abstract
To the Editor:
Treatment adherence in children with atopic dermatitis is poor despite the motivation engendered by visible, symptomatic lesions that affect sleep and school performance. 1 Surely, parents would treat their children’s disabling skin disease, wouldn’t they? To better understand the limited impact of motivation on adherence and explore potential adherence improvement methods in dermatological patients, we reviewed adherence to 6-mercaptopurine (6MP) maintenance therapy in pediatric patients with acute lymphoblastic leukemia (ALL) patients, one of the most motivated patient cohorts for adherence.
The review was developed according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. It was registered with PROSPERO (CRD42022384733). Search platforms consisted of MEDLINE PubMed, Scopus, CORE, JSTOR, and DOAJ databases. Keywords included “adherence,” and “6-mercaptopurine,” and “acute lymphoblastic leukemia.” Only primary research methodologies were included. For articles that met eligibility criteria, study length, number of patients, patient cohort classification, adherence measurement method, and adherence rates were recorded.
Four hundred and twelve articles resulted from the search. Forty-six studies were removed for being a duplicate and 340 for irrelevance. Twenty-six studies were examined and of these, 22 studies were conducted on pediatric patients, 3 on pediatric and adult patients, and 1 on adult patients.
Patients were frequently poorly adherent to this potentially life-saving medication (Supplemental Table 1). In a 15-month longitudinal study of 139 patients (7, 19 years of age), 40.8% were nonadherent to daily 6MP maintenance therapy according to metabolite profiles. 2 Twenty-seven (37%) of the 73 patients suddenly stopped medication completely in a retrospective chart review at a single-center institution; out of 41 episodes of undue medication cessation, over half (21) were initiated by family members without medical advice. 3 In a prospective cohort of 39 patients, 33.3% and 16.6% were classified as nonadherent on surveys and metabolite profiles, respectively. The greater adherence assessed by metabolic profile likely indicates patients were adherent to their medication just before the appointment but were less consistently adherent between treatment visits. 4
Good adherence to 6-MP maintenance treatment can prevent the recurrence of acute lymphoblastic leukemia. It seems safe to assume that patients and their parents/caregivers would not want leukemia to recur. However, even in our most motivated patient populations, adherence is not complete. A limitation of this review was the varying metrics through which adherence is measured; however, despite the various methods used (including self-report which often overestimates adherence), poor levels of adherence were consistently identified. Motivation alone is insufficient to assure adherence. More needs to be done. Simplifying treatment regimens, addressing patients’ preferences, creating a sense of accountability, and using triggers and other reminders are among the many approaches that we learned from ALL patients that may enhance treatment adherence and outcomes in our dermatological patients. 1,5
Supplemental Material
Table S1 - Supplemental material for What Adherence to 6-Mercaptopurine in Patients With Acute Lymphoblastic Leukemia Tells Us: A Systematic Review
Supplemental material, Table S1, for What Adherence to 6-Mercaptopurine in Patients With Acute Lymphoblastic Leukemia Tells Us: A Systematic Review by Nilesh Kodali, Isabella Blanchard, Mallory L. Zaino and Steven R. Feldman in Journal of Cutaneous Medicine and Surgery
Supplemental Material
Supplementary Material 1 - Supplemental material for What Adherence to 6-Mercaptopurine in Patients With Acute Lymphoblastic Leukemia Tells Us: A Systematic Review
Supplemental material, Supplementary Material 1, for What Adherence to 6-Mercaptopurine in Patients With Acute Lymphoblastic Leukemia Tells Us: A Systematic Review by Nilesh Kodali, Isabella Blanchard, Mallory L. Zaino and Steven R. Feldman in Journal of Cutaneous Medicine and Surgery
Supplemental Material
Figure S1 - Supplemental material for What Adherence to 6-Mercaptopurine in Patients With Acute Lymphoblastic Leukemia Tells Us: A Systematic Review
Supplemental material, Figure S1, for What Adherence to 6-Mercaptopurine in Patients With Acute Lymphoblastic Leukemia Tells Us: A Systematic Review by Nilesh Kodali, Isabella Blanchard, Mallory L. Zaino and Steven R. Feldman in Journal of Cutaneous Medicine and Surgery
Footnotes
Data Availability
Declaration of Conflicting Interests
The authors declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: Feldman has received research, speaking and/or consulting support from Eli Lilly and Company, GlaxoSmithKline/Stiefel, AbbVie, Janssen, Alovtech, vTv Therapeutics, Bristol-Myers Squibb, Samsung, Pfizer, Boehringer Ingelheim, Amgen, Dermavant, Arcutis, Novartis, Novan, UCB, Helsinn, Sun Pharma, Almirall, Galderma, Leo Pharma, Mylan, Celgene, Ortho Dermatology, Menlo, Merck & Co, Qurient, Forte, Arena, Biocon, Accordant, Argenx, Sanofi, Regeneron, the National Biological Corporation, Caremark, Teladoc, BMS, Ono, Micreos, Eurofins, Informa, UpToDate and the National Psoriasis Foundation. He is founder and part owner of Causa Research and holds stock in Sensal Health. Kodali, Blanchard, and Zaino have no conflicts of interest to disclose.
Funding
The authors received no financial support for the research, authorship, and/or publication of this article.
Supplemental Material
Supplemental material for this article is available online.
References
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
