Page 64 - Haematologica-April 2018

R. Le Calloch et al. Introduction
Polycythemia vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms (MPN) arising from the clonal expansion of a multipotent hematopoietic stem cell, causing deregulated proliferation of myeloid lineages. Therapeutic management of these chronic pathologies has two objectives: reduction of the thrombotic risk induced by blood hyperviscosity (short-term) and reduction of the risk of transformation into myelofibrosis or acute myeloid leukemia (long-term).1 Available treatments are adminis- tered orally (hydroxycarbamide, pipobroman, anagrelide or ruxolitinib) or subcutaneously (pegylated interferon), usually in combination with antithrombotic drugs.
The problem of lack of adherence to treatment is likely as old as the practice of medicine, as indicated by Hippocrates’ statement that “Patients often lie when they say that they take their medication”. The World Health Organization reported that “improving patient adherence to chronic treatment should be more beneficial than any biomedical discovery”.2 Because anticancer drugs can sig- nificantly increase patients’ survival, some cancers have become chronic diseases. Most drugs are costly, induce side effects and their efficacy frequently depends on the dose. For these reasons, adherence to cancer therapy is critical for an optimal benefit-risk ratio. Adherence to treatment has been extensively studied in asthma and dia- betes, but few studies have approached this issue in patients with malignant diseases.3
The impact of non-adherence on the achievement of sustained remission was observed in patients with chronic myeloid leukemia in whom poor adherence to imatinib therapy may be the predominant reason for not reaching an optimal molecular response.4-8 No “gold standard” exists to measure adherence, but a minimum of 90% drug intake was described as a good cut-off to discriminate treatment-adherent versus non-adherent patients.7,9-11 In a meta-analysis, Noens et al. showed that the rate of treat- ment non-compliant patients with chronic myeloid leukemia was variable (from 3% to 56%), depending on the evaluation method. Adherence to hydroxycarbamide therapy has been studied in patients with sickle cell dis- ease and appears suboptimal in most cases; better adher- ence was associated with improved clinical and economic outcomes.12
To the best of our knowledge, adherence to treatment has not been studied in PV or ET patients. We conducted a prospective clinical study to analyze adherence rates, reasons for non-adherence including the impact of previ- ous complications and the influence of non-adherence on the clinical outcome of PV and ET patients.
Methods
Recruitment of patients
Between December 2014 and December 2015, adult patients followed for PV or ET at the Institut de Cancéro-Hématologie (CHRU of Brest, France) and treated with oral (group 1) or subcutaneous (group 2) cytoreductive therapies for more than 6 months were enrolled in the OUEST study (NCT02893410). All patients signed informed consent to participation in the study, which was approved by the regional authorities of the Ethics Committee “CPP Ouest V” dated 04/09/2014, pursuant to Article L.1121-1 of the Code of Public Health, and has been declared to the
Commission Nationale Informatique et Libertés (CNIL) (N. 13809*03). We excluded patients treated for other MPN, patients who did not receive any treatment and those with physical or mental disabili- ties who were unable to consent and complete the questionnaire. These patients were identified by their inclusion in the “OBENE” observational registry for patients diagnosed with and treated for Philadelphia-negative MPN at our hospital (NCT02897297).
Questionnaire and data collected
This single-center prospective study was based on a closed questionnaire (with simple and multiple-choice questions) given to the patient at the end of a consultation or sent by e-mail. The questionnaire varied according to the route of administration of the cytoreductive drugs (oral or subcutaneous) (Online Supplementary Figure S1). The questionnaires were validated by both the Scientific and Ethical Committees of our hospital. A com- plete blood count was also performed at the time the question- naire was administered.
The questionnaire was filled in by patients, the results of com- plete blood counts were collected and sent directly to the data ana- lyzers. Consultants were not allowed to know which patients were or were not adherent to treatment.
Non-adherence to drug prescription was defined by at least three omissions of medication during the preceding month (repre- senting ≥10% of the dose) for the group treated orally (group 1) and omission of at least one injection during the two preceding months for the subcutaneously treated group (group 2).
These definitions were chosen in accordance with the cut-offs identified by Marin et al.6
The patients were followed prospectively and new events (thrombosis, hematologic evolution and death) were recorded at the end of the study on February 1, 2017. At that point, the patients’ identities were revealed to the consultants and the global analyses were performed.
Statistical methods
The responses were analyzed using conventional descriptive parameters. The response items were described in terms of fre- quency for qualitative responses and as the median ± the extreme values for quantitative answers. Statistical analyses were per- formed by the Clinical Investigation Center of Brest Hospital (INSERM CIC 1412) using SAS software (SAS, Brie Comte Robert, France). The data were compared using the chi-square test for qualitative parameters and non-parametric tests for quantitative parameters. A P value <0.05 was considered statistically signifi- cant. The risks of thrombosis and transformation were analyzed by calculating the hazard ratios between treatment-adherent and non-adherent patients.
Results
Description of the population study
We included 286 patients in the study: 136 (47.6%) with PV and 150 (52.4%) with ET as their initial diagnoses. The sex ratio was 0.74 in the whole cohort (164 males, 122 females). Of the 286 patients, 233 (81.5%) received their treatment orally (group 1) and 53 (18.5%) received it sub- cutaneously (group 2). All the patients’ characteristics are summarized in Table 1.
Before completion of the questionnaire, most patients had experienced a complication related to their MPN: thrombotic events before or at diagnosis of MPN in 31.8% (74/233) and 18.9% (10/53) of patients in group 1 and 2, respectively, and between diagnosis and inclusion in the
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