Al-Dewik Nader I, Morsi Hisham M, Samara Muthanna M, Ghasoub Rola S, Gnanam Cinquea C, Bhaskaran Subi K, Nashwan Abdulqadir J, Al-Jurf Rana M, Ismail Mohamed A, AlSharshani Mohammed M, AlSayab Ali A, Ben-Omran Tawfeg I, Khatib Rani B, Yassin Mohamed A
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.
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.
Clin Med Insights Oncol. 2016 Oct 2;10:95-104. doi: 10.4137/CMO.S32822. eCollection 2016.
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.
This study investigates the correlation between patient adherence and failure of TKIs' treatment in a follow-up study.
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 of transcripts in peripheral blood. Response is classified at the hematological, cytogenetic, and molecular levels into optimal, suboptimal, or failure.
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%; < 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.
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.
尽管引入酪氨酸激酶抑制剂(TKIs),如甲磺酸伊马替尼(IM),用于治疗慢性粒细胞白血病(CML)取得了革命性的成功,但仍有相当一部分患者的治疗失败。
本研究在一项随访研究中调查患者依从性与TKIs治疗失败之间的相关性。
这是一项对一组新的CML患者进行的随访研究。使用药物事件监测系统(MEMS 6 TrackCap,AARDEX有限公司)评估对IM的依从性。采用9项Morisky药物依从性量表、药物持有率(MPR)计算以及电子病历,以识别影响依从性的潜在因素。根据欧洲白血病网2013年指南,通过逆转录酶定量聚合酶链反应测量外周血中转录本水平来评估临床结局。反应在血液学、细胞遗传学和分子水平上分为最佳、次优或失败。
共有36例CML患者(5名公民和31名非公民居民)同意参与本研究。MEMS总体平均得分为89分。在这36例患者中,22例(61%)被归类为依从(平均:95分),14例(39%)被归类为不依从(平均:80.2分)。与不依从组(14.3%;P<0.0001)相比,依从患者获得最佳反应的可能性显著更高(95%)。使用MEMS测得的不依从率高达39%,这与37%的治疗失败率相关。调查结果显示,97%的患者在感觉不适时自行增加了IM剂量,31%的患者在想起时服用了漏服的IM剂量。其他已知影响依从性的因素表明,一半的患者出现了一种或多种副作用,65%的患者资金不足,13%的患者称在国家癌症控制与研究中心药房无法获得该药物,72%的患者认为IM能治愈疾病。MPR结果显示,16%的患者通过医院药房获取治疗药物的情况不佳。
这是第一项评估卡塔尔CML患者对IM的依从性和反应的前瞻性研究。卡塔尔观察到的高治疗失败率可归因于依从性差。经济因素(药物价格难以承受)是不依从的主要原因之一,当地应努力改善癌症疾病药物的可及性。通过密切监测和剂量调整,可以改善与不依从相关的其他风险因素。监测不依从的风险因素以及对患者进行教育,包括医疗团队、医生、护士、药剂师和患者之间的直接沟通,是使TKI治疗效益最大化并纠正这一问题的重要组成部分。初步结果表明,患者对治疗的反应可能与患者对治疗的依从性直接相关。然而,可能需要在更大的队列中进行进一步深入和具体的分析。