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MPN patients’ non-adherence to treatment
shown in other pathologies, the cohort was prospectively followed for an additional median time of 1.8 years (range, 1-2.4).
During the follow-up period, we recorded new events in 35/286 patients (12.2%), among whom 32/35 (91%) were in group 1. The recorded events were thrombosis in 18 cases (6.3%; 12 arterial, 6 venous), phenotypic evolu- tion in 7 (2.4%; 1 case of post-ET PV, 3 cases of secondary myelofibrosis and 3 cases if secondary acute myeloid leukemias) and death in 17 cases (5.9%), all occurring in group 1 (P=0.05) (Table 3).
In the whole cohort, non-adherence to cytoreductive therapy was associated with a significant reduction in the complete hematologic remission rate compared to that in the group adhering to treatment: 50.8 versus 65.2% (P=0.03) (ORR=1.85, 95% CI: 1.01-3.36). This difference was lost when analyzing groups 1 and 2 separately (Table 2).
No significant association was found between non- adherence and thrombosis or death. In group 2, non- adherence was not significantly associated with the out- come, but there were only a few events in this group. However, non-adherence to cytoreductive therapy was associated with an increased risk of hematologic transfor- mation both in the whole cohort [4/65 (6.1%) versus 3/221 (1.3%), P=0.05; ORR=4.73, 95% CI: 0.78-33.14] and in group 1 [4/55 (7.3%) versus 3/178 (1.8%), P=0.05; ORR=4.54, 95% CI: 1-31.98]. Furthermore, these evolu- tions also occurred sooner in the treatment non-adherent group (P=0.05) (Figure 2).
Discussion
The importance of treatment compliance has now been clearly established in many pathological conditions, and especially in hematologic malignancies.9,13-16 These studies typically demonstrate that poor adherence has a negative impact on clinical evolution. However, to the best of our knowledge, no such data were previously available regarding patients with Philadelphia-negative MPN. Yet, these chronic disorders have very variable clinical evolu- tion and are prone to complications. We, therefore, decid- ed to assess MPN patients’ compliance with cytoreductive and antithrombotic treatments.
Many ways of assessing patients’ adherence to treat-
ment have been described, including pill counts, drug plas- ma levels, various microelectronic monitoring systems and dispensation by a third party. All methods have their pros and cons. We chose to assess patients’ adherence using a single questionnaire. The self-evaluation method using a questionnaire is easier and less expensive to imple- ment, even though patients’ reluctance to admit omitting drug intake could theoretically bias the results. Because of the blind process of this study, there was no influence from the consultant or staff on completion of the ques- tionnaires. We cannot, however, exclude some degree of under-declaration of non-adherence. Despite this fact, the proportion of patients not adherent with treatment in this study was equivalent to that reported by Marin et al. who used a microelectronic monitoring system, suggesting that
Table 3. New events observed after completion of the questionnaires. Non-adherent Adherent P
Whole cohort
N. of patients Events (n/%)
Total Thrombosis Evolution Death
Group 1
N. of patients Events (n/%)
Total Thrombosis Evolution Death
Group 2
N. of patients Events (n/%)
Total Thrombosis
Evolution
Death
286
35 (12.2) 18 (6.3) 7 (2.4) 17 (5.9)
233
32 (13.7) 16 (6.9) 7 (3) 17 (7.3)
patients
65
8 (12.3) 4 (6.1) 4 (6.1) 2 (3.1)
55
7 (12.7) 3 (5.6) 4 (7.3) 2 (3.7)
patients
221
27 (12.2) 0.98 14 (6.3) 1
3 (1.4) 0.05 15 (6.8) 0.37
178
25 (14) 0.8 13 (7.3) 0.77 3 (1.8) 0.05 15 (8.4) 0.37
53 10 43
3 (5.7) 2 (3.8) 0
1 (10) 1 (10) 0
2 (4.7) 0.47 1 (2.3) 0.34
0 na
0 0 0 na
na: non-applicable; n: number; pts: patients; %: percent.
the questionnaire does not grossly underestimate non-
Figure 1. Reasons for non-adherence. Gray repre- sents the answers of patients from group 1 (oral intake) and black represents the answers of patients from group 2 (sub-cutaneous injection). The results are expressed as percentage of answers. Patients could state more than one reason for non-adherence. FBC: full blood count.
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