Chronic myeloid leukemia patients’ adherence to peroral tyrosine kinase inhibitors compared with adherence as estimated by their physicians

Figures & data

Table 1 Characteristics of the CML patients on TKI medication involved in the study (n=86)

Variables
Sex, n (%)	Male	45 (52.3)
	Female	41 (47.7)
Agea (years)	Mean (SD)	57.8 (12.1)
	Median	59.0
	Range	25.0–83.0
Age at diagnosis (years)	Mean (SD)	52.7 (12.3)
	Median	52.0
	Range	19.0–79.0
Time from diagnosis (years)	Mean (SD)	5.1 (3.7)
	Median	4.0
	Range	0.5–17.0
TKI medication-related factors
TKI medication, n (%)	Imatinib	68 (79.1)
	Dasatinib	9 (10.5)
	Nilotinib	9 (10.5)
Line, n (%)	First	47 (54.7)
	Second	25 (29.1)
	Third	13 (15.1)
	Fourth	1 (1.2)
Number of TKI doses per day, n (%)	One	72 (83.7)
	Two	14 (16.3)
Visits and contacts with health personnel
MD visits in the last 12 months	Mean (SD)	2.2 (1.8)
	Median	2.0
	Range	0–12
MD visits during the first year after diagnosis	Mean (SD)	4.1 (1.5)
	Median	4
	Range	1–12
Phone contacts in the last 12 months	Mean (SD)	0.7 (1.7)
	Median	0
	Range	0–12
Adherence aids
Written treatment plan, n (%)	No	86 (100)
	Yes	0
List of medications, n (%)	No	82 (95.3)
	Yes	4 (4.7)
Pill dispenser, n (%)	No	69 (80.2)
	Yes	17 (19.8)
Mobile phone reminder, n (%)	No	76 (88.4)
	Yes	10 (11.6)
Knowledge total score, n (%)	0	28 (32.6)
	1	30 (34.9)
	2	15 (17.4)
	3	7 (8.1)
	4	4 (4.7)
	5	2 (2.3)

Note:

a At the time of adherence evaluation.

Abbreviations: CML, chronic myeloid leukemia; TKI, tyrosine kinase inhibitor; n, number; SD, standard deviation; MD, medical doctor.

Table 2 Adherence of CML patients to TKI treatment as measured by the MMAS scale (n=86)

	MMAS 8 (high)	MMAS 6–7.75 (medium)	MMAS <6 (low)	Total, n (%)
Total, n (%)	20 (23)	48 (56)	18 (21)	86 (100)
Age (years), median (range)	62 (46–82)	58 (31–83)	49 (25–82)
Sex, n (%)
Male	11 (25)	23 (52)	10 (23)	44 (100)
Female	9 (22)	25 (61)	8 (20)	42 (100)
Time from diagnosis (years)
Mean (range)	4 (1–11)	6 (1–17)	5 (1–15)
Median	3	6	3
Medication, n (%)
Imatinib	16 (24)	40 (59)	12 (18)	68 (100)
Dasatinib	1 (10)	6 (56)	3 (33)	9 (100)
Nilotinib	3 (33)	3 (33)	3 (33)	9 (100)
Line, n (%)
First	12 (26)	26 (55)	9 (19)	47 (100)
Second	5 (20)	12 (48)	8 (32)	25 (100)
Third	3 (23)	10 (77)	0	13 (100)
Fourth	0	0	1 (100)	1 (100)
Long-term doctor relationship, n (%)
Yes	15 (26)	31 (53)	12 (21)	58 (100)
No	5 (18)	17 (61)	6 (21)	28 (100)
Treatment response, n (%)
PCyRa	0	3 (100)	0	3 (100)
CCyRb	3 (23)	10 (77)	0	13 (100)
MR^3.0	9 (27)	14 (41)	11 (32)	34 (100)
MR^4.0	4 (44)	4 (44)	1 (12)	9 (100)
MR^4.5	0	7 (100)	0	7 (100)
MR^5.0	4 (20)	10 (50)	6 (30)	20 (100)

Notes: Cytogenetic responses: Partial cytogenetic response (PCyR), Ph+ metaphases 1–35%. Complete cytogenetic response (CCyR), no Ph+ metaphases or less than 1% BCR-ABL1 positive nuclei by I-FISH. Molecular responses: MR^3.0 = major molecular response = BCR-ABL1 <0.01% (IS); MR^4.0 = BCR-ABL1 ≤0.01% (IS); MR^4.5 = BCR-ABL1 ≤0.0032% (IS); MR^5.0 = BCR-ABL1 ≤0.001% (IS).²³ Response is assessed with a standardized real quantitative polymerase chain reaction and/or cytogenetics at 3 months, 6 months, and 12 months. BCR-ABL1 transcript levels ≤10% at 3 months, <1% at 6 months, and ≤0.1% from 12 months onward define optimal response, whereas >10% at 6 months and >1% from 12 months onward define failure. PCyR at 3 months and CCyR from 6 months onward define optimal response, whereas no CyR (Ph1+ >95%) at 3 months, less than PCyR at 6 months, and less than CCyR from 12 months onward define failure.²³

a Ph+ metaphases 1–35%.

b No Ph+ metaphases or less than 1% BCR-ABL1 positive nuclei by I-FISH.

Abbreviations: CML, chronic myeloid leukemia; TKI, tyrosine kinase inhibitor; MMAS, 8-item Morisky Medication Adherence Scale; n, number; CyR, cytogenetic response; MR, molecular response; Ph+, Philadelphia chromosome-positive; IS, international scale; I-FISH, interphase fluorescence in situ hybridization.

Figure 1 Nonadherent behaviors of CML patients on TKI medication as measured by items included in the MMAS (n=86).

Note: *Item contains a 5-point Likert scale (once in a while, sometimes, usually, all the time = <1 point; included in the figure).
Abbreviations: n, number; CML, chronic myeloid leukemia; TKI, tyrosine kinase inhibitor; MMAS, 8-item Morisky Medication Adherence Scale.

Table S1 Morisky Medication Adherence Scale (8-item)

You indicated that you are taking medication(s) for your chronic myelogenous leukemia. Individuals have identified several issues regarding their medication-taking behavior and we are interested in your experiences. There is no right or wrong answer. Please answer each question based on your personal experience with your chronic myelogenous leukemia medication. (Please check your response below)
	No=1	Yes=0
1. Do you sometimes forget to take your chronic myelogenous leukemia medication(s)?
2. People sometimes miss taking their medications for reasons other than forgetting. Thinking over the past 2 weeks, were there any days when you did not take your chronic myelogenous leukemia medication(s)?
3. Have you ever cut back or stopped taking your medication(s) without telling your doctor, because you felt worse when you took it?
4. When you travel or leave home, do you sometimes forget to bring along your chronic myelogenous leukemia medication(s)?
5. Did you take your chronic myelogenous leukemia medication(s) yesterday?
6. When you feel like your chronic myelogenous leukemia is under control, do you sometimes stop taking your medication(s)?
7. Taking medication(s) every day is a real inconvenience for some people. Do you ever feel hassled about sticking to your chronic myelogenous leukemia treatment plan?
8. How often do you have difficulty remembering to take all your medication(s)?
(Please circle the correct number)
Never/Rarely…………………………………… 4
Once in a while………………………………… 3
Sometimes……………………………………… 2
Usually…………………………………………… 1
All the time……………………………………… 0

© Morisky Medication Adherence Scale (MMAS-8-Item). Use of the ©MMAS is protected by US copyright laws. Permission for use is required. A license agreement is available from Donald E Morisky, ScD, ScM, MSPH, Professor, Department of Community Health Sciences, UCLA School of Public Health, 650 Charles E Young Drive South, Los Angeles, CA 90095-1772, USA.

Table S2 Physicians’ assessment of chronic myeloid leukemia patients’ adherence on the basis of the doctor–patient relationship

1. The patient uses the medication as prescribed and has no problems.

2. Problems in adherence to medication are possible.

3. The patient does not follow the treatment as prescribed. There are problems in medication use. Adherence to the medication is not optimal.

Table S3 Questions to evaluate CML patient’s knowledge of the disease and TKI treatment

Question 1. What is CML?

Question 2. What has happened in your body (the cause of CML)?

Question 3. What does the TKI medication do in your body (how does the medication work)?

Question 4. What kind of side effects might the medication cause?

Question 5. (Have you talked with your doctor?) What happens if you skip a dose/stop taking your TKI medication?

Notes: Each question has a value of 1 point. The total score will range from 0–5.

Abbreviations: CML, chronic myeloid leukemia; TKI, tyrosine kinase inhibitor.

BaccaraniMDeiningerMWRostiGEuropean LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013Blood2013122687288423803709

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