THE EFFECT OF IMATINIB MESYLATE (GLIVEC®) ADHERENCE ON TREATMENT OUTCOMES OF PATIENTS WITH CHRONIC MYELOID LEUKAEMIA IN NIGERIA

Abstract

Background: Adherence to imatinib (Glivec®) is of critical importance in achieving optimal
treatment outcome in patients with chronic myeloid leukaemia (CML).
Aims and Objective: This study aimed to investigate adherence and factors that could
influence adherence to Glivec®. The objective was to evaluate haematologic, clinical,
cytogenetic, and molecular response; and to assess the relationship between Glivec®
adherence and these responses.
Methodology: A longitudinal study involving 70 consenting and newly diagnosed patients
with CML in chronic phase. All the patients received Glivec® at 400mg/day, and were
counselled on adherence and informed on follow-up for adherence assessment. A structured
and self-administered questionnaire with the nine-item Morisky Medication Adherence Scale
(MMAS) was used as the tool to assess adherence. In addition, a follow-up questionnaire was
administered to identify personal factors known to influence adherence to therapy. Response
to therapy was assessed by clinical and haematological parameters using full blood count and
differentials, spleen and liver size evaluation at 3 months and at 6 months of initiating
therapy. Cytogenetic and molecular responses were also evaluated using Ph chromosome and
BCR-ABL transcript levels respectively at 6 months of initiating therapy.
Data was analysed using SPSS version 21.0 statistical package (2012, IBM Corp, Armonk,
NY, USA.). Continuous variables were compared using descriptive (means, standard
deviation, median) and inferential statistics (chi square, Fisher‘s exact probability and t test)
as appropriate. The level of significance for all statistical analysis was set at p
Results: The age range of the participants was 18 to 78 with a median age of 38 years. There
were 44 (62.9%) males and 26 (37.1%) females with a male to female (M: F) ratio of 1.7:1.
The range of adherence score was 5 to 13 with a median score of 10. Thirty-three (47.1%) of
the patients classified as adherent had a statistical significant relationship with family support
(p= 0.008). To determine the influence of distance to the hospital on adherence, we classified
the subjects according to whether they live more than 200 kilometres (km) away from the
hospital or not. Of the 70 subjects, 35 live more than 200 km away from the hospital. Of
these 35, 24(64.9%) were from the non-adherent group. Of the 35 that live less than 200 km
away from the hospital, 13 (35.1%) were from the non-adherent group. Distance of more than
200 km away from the hospital was significantly associated with non-adherence to Glivec
therapy (p= 0.008). Of the 37(52.9%) classified as non-adherent, 24% sometimes forgot to
take their drugs, 27% missed drugs without justifiable reasons (careless with medication),
30% travelled without the medication and 13% admitted to interrupting their daily medication
intake due to side effects. Assessment of patients after six months of Glivec® treatment
showed persisting splenomegaly in one (3.0%) patient in the adherent group and six (16.7%)
patients in the non-adherent group (p = 0.06). While hepatomegaly was absent in the adherent
group; two (5.6%) patients in the non-adherent group still had persistent hepatomegaly at six
months of therapy (p = 0.17). Of the 54 (77.1%) patients that achieved complete
haematologic remission (CHR) at 3 months, 84.8% were adherent while 70.3% were non
adherent (p = 0.15). At 6 months of therapy a total of 56 (80%) patients achieved CHR,
irrespective of the adherence status. Notable, though not statistically significant is that many
more patients that were adherent achieved major molecular response (MMR) in less than a
year compared to non-adherent group (46.9% vs. 25.0%) (p = 0.16).
Conclusion: This study found that a higher proportion of patients were non-adherent to
Glivec® therapy, and distance of more than 200 km away from the hospital is significantly
associated with non-adherent to Glivec therapy. However, amongst those that were adherent,
a higher proportion were found to have family support which is a significant determinant of
adherence in this study. Therefore there is a strong need for social support in CML patients to
improve adherence. Of prognostic importance in this study, a higher proportion of those who
achieved CHR and major molecular response (MMR) were adherent to Glivec®.