Guérin Annie, Chen Lei, Dea Katherine, Wu Eric Q, Goldberg Stuart L
Analysis Group Inc. , Boston, MA , USA.
Curr Med Res Opin. 2014 Jul;30(7):1345-52. doi: 10.1185/03007995.2014.904281. Epub 2014 Mar 21.
Adherence with oral tyrosine kinase inhibitor (TKI) therapy over prolonged timeframes is required for successful outcomes among patients with chronic phase chronic myelogenous leukemia (CP-CML). Since quantitative polymerase chain reaction (qPCR) monitoring may identify early suboptimal responses, and thereby permit detection of non-adherence to therapy, we sought to assess the association between frequency of molecular monitoring and medication adherence.
This is a retrospective cohort study design of diagnosed CP-CML obtained from two large US administrative claims databases. Patients were grouped into cohorts based on the number of qPCR tests they had. Adherence was assessed both by medication possession ratio (MPR) and proportion of days covered (PDC) and was compared between qPCR cohorts. A sensitivity analysis was performed by adjusting for the number of oncology outpatient visits not due to routine molecular monitoring.
Over the 12 month study period, 1205 CML patients met the selection criteria; 41.0% had no qPCR tests, 31.9% had 1-2 tests, and 27.1% had 3-4 tests; 88.9% of patients were initiated on imatinib. Patients in the 3-4 qPCR tests cohort had an average MPR that was 10.22 (p < 0.001) and 9.54 (p < 0.001) percentage points higher compared to patients in the 0 tests cohort and the 1-2 tests cohort. When using PDC as a measure of adherence, similar results were obtained. The results of the sensitivity analysis were consistent with core analysis findings, excluding number of physician visits as a potential driver of adherence.
These findings demonstrate an association, not causation, between molecular monitoring frequency and adherence.
Frequent molecular monitoring (3-4 times per year as recommended in current guidelines) is associated with greater TKI treatment adherence for patients diagnosed with CML. Since TKI adherence >80% has been associated with better clinical outcomes, this study underscores the importance of molecular monitoring.
慢性期慢性髓性白血病（CP-CML）患者要想获得成功的治疗结果，需要长期坚持口服酪氨酸激酶抑制剂（TKI）治疗。由于定量聚合酶链反应（qPCR）监测可能会识别出早期的次优反应，从而发现治疗依从性不佳的情况，我们试图评估分子监测频率与药物依从性之间的关联。
这是一项回顾性队列研究，数据来自美国两个大型行政索赔数据库中确诊的CP-CML患者。根据患者进行qPCR检测的次数将其分组。通过药物持有率（MPR）和覆盖天数比例（PDC）评估依从性，并在不同qPCR检测队列之间进行比较。通过调整非因常规分子监测而进行的肿瘤门诊就诊次数进行敏感性分析。
在为期12个月的研究期间，1205例CML患者符合入选标准；41.0%的患者未进行qPCR检测，31.9%的患者进行了1-2次检测，27.1%的患者进行了3-4次检测；88.9%的患者开始使用伊马替尼治疗。与未进行检测的队列和进行1-2次检测的队列相比，进行3-4次qPCR检测的队列患者的平均MPR分别高出10.22个百分点（p<0.001）和9.54个百分点（p<0.001）。以PDC作为依从性衡量指标时，也得到了类似结果。敏感性分析结果与核心分析结果一致，排除了医生就诊次数作为依从性潜在驱动因素的影响。
这些发现表明分子监测频率与依从性之间存在关联，但并非因果关系。
对于确诊为CML的患者，频繁的分子监测（按照当前指南建议每年3-4次）与更高的TKI治疗依从性相关。由于TKI依从性>80%与更好的临床结果相关，本研究强调了分子监测的重要性。
