title: Is Adherence to Imatinib Mesylate Treatment Among Patients with Chronic Myeloid Leukemia Associated with Better Clinical Outcomes in Qatar?
abstract: BACKGROUND
  Despite the revolutionary success of introducing tyrosine kinase inhibitors (TKIs), such as imatinib mesylate (IM), for treating chronic myeloid leukemia (CML), a substantial proportion of patients' treatments fail.
  
  
  OBJECTIVE
  This study investigates the correlation between patient adherence and failure of TKIs' treatment in a follow-up study.
  
  
  METHODS
  This is a follow-up study of a new cohort of CML patients. Adherence to IM is assessed using the Medication Event Monitoring System (MEMS 6 TrackCap, AARDEX Ltd). The 9-item Morisky Medication Adherence Scale, medication possession ratio (MPR) calculation, and the electronic medical records are used for identifying potential factors that influence adherence. Clinical outcomes are assessed according to the European Leukemia Net 2013 guidelines via reverse transcriptase quantitative polymerase chain reaction measurement of the level ofBCR-ABL1transcripts in peripheral blood. Response is classified at the hematological, cytogenetic, and molecular levels into optimal, suboptimal, or failure.
  
  
  RESULTS
  A total of 36 CML patients (5 citizens and 31 noncitizen residents) consented to participate in the study. The overall mean MEMS score was 89. Of the 36 patients, 22 (61%) were classified as adherent (mean: 95) and 14 (39%) were classified as nonadherent (mean: 80.2). Adherent patients were significantly more likely to obtain optimal response (95%) compared to the nonadherent group (14.3%;P< 0.0001). The rate of poor adherence was as high as 39% using MEMS, which correlates with 37% treatment failure rate. The survey results show that 97% of patients increased the IM dose by themselves when they felt unwell and 31% of them took the missing IM dose when they remembered. Other factors known to influence adherence show that half of patients developed one or more side effects, 65% of patients experienced lack of funds, 13% of patients declared unavailability of the drug in the NCCCR pharmacy, and 72% of patients believed that IM would cure the disease. The MPR results reveal that 16% of patients had poor access to treatment through the hospital pharmacy.
  
  
  CONCLUSIONS
  This is the first prospective study to evaluate CML patients' adherence and response to IM in Qatar. The high rate of treatment failure observed in Qatar is explained by poor adherence. An economic factor (unaffordable drug prices) is one of the main causes of nonadherence and efforts should be made locally to improve access to medication for cancer diseases. Other risk factors associated with poor adherence could be improved by close monitoring and dose adjustment. Monitoring risk factors for poor adherence and patient education that include direct communication between the health-care teams, doctors, nurses, pharmacists, and patients are essential components for maximizing the benefits of TKI therapy and could rectify this problem. The preliminary results show that patients' response to treatment may be directly linked to patients' adherence to treatment. However, further in-depth and specific analysis may be necessary in a larger cohort.
authors.affiliation: Qatar Medical Genetics Center, Hamad General Hospital (HGH), Hamad Medical Corporation, Doha, Qatar.; National Center for Cancer Care and Research (NCCCR), Hamad Medical Corporation, Doha, Qatar.; Interim Translational Research Institute (iTRI), Hamad Medical Corporation, Doha, Qatar.; Faculty of Health and Social Care Sciences, Kingston University and St. George's University of London, London, UK.
authors.forename: Nader I
authors.initials: NI
authors.lastname: Al-Dewik
authors.affiliation: Faculty of Health and Social Care Sciences, Kingston University and St. George's University of London, London, UK.; Academic Health System, Hamad Medical Corporation, Doha, Qatar.; Quality of Life Unit, Hamad Medical Corporation, Doha, Qatar.
authors.forename: Hisham M
authors.initials: HM
authors.lastname: Morsi
authors.affiliation: Department of Psychology, Kingston University, London, UK.
authors.forename: Muthanna M
authors.initials: MM
authors.lastname: Samara
authors.affiliation: National Center for Cancer Care and Research (NCCCR), Hamad Medical Corporation, Doha, Qatar.
authors.forename: Rola S
authors.initials: RS
authors.lastname: Ghasoub
authors.affiliation: National Center for Cancer Care and Research (NCCCR), Hamad Medical Corporation, Doha, Qatar.
authors.forename: Cinquea C
authors.initials: CC
authors.lastname: Gnanam
authors.affiliation: National Center for Cancer Care and Research (NCCCR), Hamad Medical Corporation, Doha, Qatar.
authors.forename: Subi K
authors.initials: SK
authors.lastname: Bhaskaran
authors.affiliation: National Center for Cancer Care and Research (NCCCR), Hamad Medical Corporation, Doha, Qatar.
authors.forename: Abdulqadir J
authors.initials: AJ
authors.lastname: Nashwan
authors.affiliation: Interim Translational Research Institute (iTRI), Hamad Medical Corporation, Doha, Qatar.
authors.forename: Rana M
authors.initials: RM
authors.lastname: Al-Jurf
authors.affiliation: Interim Translational Research Institute (iTRI), Hamad Medical Corporation, Doha, Qatar.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Ismail
authors.affiliation: Molecular Genetics Laboratory, Hamad Medical Corporation, Doha, Qatar.
authors.forename: Mohammed M
authors.initials: MM
authors.lastname: AlSharshani
authors.affiliation: Interim Translational Research Institute (iTRI), Hamad Medical Corporation, Doha, Qatar.; Primary Health Care Center (PHCC), Hamad Medical Corporation, Doha, Qatar.
authors.forename: Ali A
authors.initials: AA
authors.lastname: AlSayab
authors.affiliation: Qatar Medical Genetics Center, Hamad General Hospital (HGH), Hamad Medical Corporation, Doha, Qatar.
authors.forename: Tawfeg I
authors.initials: TI
authors.lastname: Ben-Omran
authors.affiliation: Medicines Management and Pharmacy Services, Leeds Teaching Hospitals, NHS Trust, Leeds, UK.; Faculty of Medicines and Health, LICAMM, University of Leeds, Leeds, UK.
authors.forename: Rani B
authors.initials: RB
authors.lastname: Khatib
authors.affiliation: National Center for Cancer Care and Research (NCCCR), Hamad Medical Corporation, Doha, Qatar.
authors.forename: Mohamed A
authors.initials: MA
authors.lastname: Yassin
keywords: 9-item Morisky Medication Adherence Scale; ABL1; BCR-ABL1 mutations; Medication Event Monitoring System; adherence; chronic myeloid leukemia; imatinib mesylate; medication possession ratio; reverse transcriptase quantitative polymerase chain reaction; treatment response BCR-ABL1