Adherence to Imatinib in Patients with Chronic Myeloid Leukemia in the Congo

Research Article

Austin Hematol. 2017; 2(1): 1011.

Adherence to Imatinib in Patients with Chronic Myeloid Leukemia in the Congos

Okouango Nguelongo Ova JD, Elira Dokekias A and Ngolet LO*

Clinical Hematology Unit, Marien Ngouabi University, Brazzaville, Republic of Congo

*Corresponding author: Ngolet LO, Clinical Hematology Unit, Marien Ngouabi University, Brazzaville, Republic of Congo

Received: April 14, 2017; Accepted: May 15, 2017; Published: May 22, 2017


Background: Adherence to imatinib in Chronic Myeloid Leukemia (CML) leads to optimal cytogenetic and molecular responses. Studies on this subject in Western countries have shown various results. The Glivec (imatinib) International Patient Assistance Program has been distributing at no cost the imatinib in 28 African countries. Cytogenetic and molecular responses to imatinib in patients eligible for this program remain poorer than expected. Non-adherence to imatinib is surveyed. The aim of this study is to assess the adherence and therapeutic persistence of imatinib in patients with chronic myeloid leukemia in Congo.

Patients and Methods: We studied imatinib adherence among 52 chronic myeloid leukemia patients with an average of 36.6 years (range 14 and 62 years) diagnosed at the chronic phase. The adhesion was evaluated through 3 different indirect methods:

1. Patients interview using the Morisky questionnaire (MMAS)

2. MPR

3. Discontinuation

The survival curve was determined for each group of patients: adherent and non adherent.

Results: Twenty-nine patients (55.76%) reported adherence to imatinib (MMAS>6), while the calculation of the number of imatinib capsules provided indicated that only 25% of patients were actually adherent (MPR>85%). Nonadherence according to MPR was associated with adolescent age (p = 0.002) and duration of treatment (p = 0.01). Progression of the disease was observed in 23 patients (43.23%). of these, 18 (78.3%) were non-adherent to treatment. Twenty-three patients discontinued treatment (43.23%). The average duration of interruption was 99 days. The average survival time at 60 months was 38% for the non-adherent group versus 82% for the adherent group.

Conclusion: Adherence to imatinib appears to be low. Different cultural, socio-economic, clinical and therapeutic factors are involved in non-adherence to the imatinib. They need to be identified in order to implement strategies to accompany patients.

Keywords: Adherence; Imatinib; Chronic myeloid leukemia; Congo


Patient adherence to recommended treatment regimen leads to a good quality outcome. Despite this fact the patient’s adherence remains debatable. Adherence is poor, especially when the drug is taken orally [1]. Imatinib is an oral cancer therapy that has yielded impressive cytogenetic and molecular responses in CML [2]. It is a specific inhibitor of the tyrosine kinase that has demonstrated a significant activity in all phases of the Myeloid Chronic Leukemia (CML) [3]. Suboptimal responses are linked to high adherence to imatinib. However, the degree to which patients adhere to the imatinib is varies. Studies on the topic reported disparate results that range from 14 to 97% [4-9].

In the Sub Saharan region, the question of adherence to imatinib is unknown. Since early 2002, 28 African countries are eligible for the imatinib compassionate program that provides the drug at no cost. Consequently, imatinib is the first line treatment of CML in these countries. However, despite free, sustainable access to the drug by patients eligible for the compassionate program, reports on outcome and cytogenetic responses showed low performance [10-13]. We have made the hypothesis that poor outcome of patients under imatinib is linked to poor adherence to the treatment. Therefore, we report through this first study carried out in the African region, the adherence of imatinib to patients with CML in the Congo.

Material and Methods

Study design

GIPAP was implemented in the department of Hematology which is a tertiary medical facility that manages and monitors patients with CML since 2005. All patients with CML that was documented by cytogenetic studies are supplied at no cost with imatinib. Records of CML patients from 2008 to 2016 were reviewed to calculate the Overall Survival (OS) of adherent and non-adherent patients. OS is defined as the time elapsed between the imatinib initiations to death due to any cause.

From June 2015 to June 2016, we interviewed once each patient on imatinib 400 mg daily for at least one month to assess adherence to the imatinib and calculated the imatinib possession ratio and discontinuation delay during this time frame. Hematological response is monitored monthly during the first six months and then depending on the response every two or three months. The cytogenetic response was monitored at 6 months of treatment. For each Chronic Phase (CP) CML patient under imatinib for at least three months with a 400 mg daily dosage, we collected socio-demographic and clinical data from the medical record.

The study was approved the ethic committee of Brazzaville. All participants gave their written consents before participating in the study.

Data collection

Adherence: Adherence to imatinib was assessed by three indirect collection methods:

1. Questionnaire: Patients were interviewed individually by one hematologist of the department of Hematology. A questionnaire adapted from the eight item medication adherence scale by Morisky et al. was submitted to patients [14]. The interview was lead in French or local dialects depending on the participant’s choice. The Morisky et al. questionnaire includes 8 items that identify the barrier to non adherence. The 8 items consist of seven questions with yes and no answers and one item (the last one) with a 5-point Liker scale. Each item measures a specific medication taking behavior. MMAS score ranges from 0 to 8 and is classified in three levels. Score of 8 indicates high adherence, medium adherence between 6-7.75 and score <6 low adherence [14]. In this study, non adherence was defined by MMAS-8 inferior to 6 (75%) and adherence MMAS-8 = 6.

2. Medication Ratio Possession (MPR): MPR is the ratio between the number of days during which imatinib was acquired divided by the number of days between the first and the last acquisition of the imatinib. We calculated the MPR by dividing the number of imatinib possession by 365 days X 100. According to previous research studies on imatinib adherence a MPR of 85% was considered a midpoint threshold [7,15]. Consequently; patients were considered adherent to imatinib if they maintained an average of 85% or higher; they were considered non adherent when the MPR was inferior to 85%.

3. Discontinuation: Is defined as the gap period noticed without medication possession or the time during which the patient remains untreated for no medical reason. Discontinuation was reported when it was a 90 days or more gap [15]. It was measured by counting the total of days between the last refill and the date when the patient showed up at the Hematology Unit for a new refill. Patients for whom no gap was noticed where defined as persistent.

Statistical analysis

For the description of each quantitative variable, the average, range, frequencies and percentages were calculated. Odds Ratio (OR) and their 95% are presented for all quantitative variables. Fisher test was performed to study the patient’s adherence and factors influencing it. A significance level of p=<0.05 was considered. Analysis survival was calculated using the Kaplan-Meier method.


Socio demographic data

52 patients were included in the study. They were 34 male (65.4%) and 18 female (34.6%).The mean age was 36.6 years (extreme 164and 62years). The characteristics of the patients are shown in Table 1.