Chronic myeloid leukaemia (CML) is a myeloproliferative disorder that accounts for 15% of all leukaemias.1 The proliferating cells of this haematological neoplasm are characterised by the presence of the so-called Philadelphia chromosome, the result of a reciprocal translocation between chromosomes 9 and 22 with a rearrangement of the BCR-ABL gene, which encodes a protein with high constitutive tyrosine kinase activity.1

Until the development of tyrosine kinase inhibitors (TKIs), CML was a disease with a low survival rate. However, the advent of these drugs has changed the outlook for this disease, achieving responses and survival rates that often allow CML to become a chronic process.2 TKIs are oral antineoplastic drugs that give patients freedom and autonomy compared to intravenous drugs, thus improving their quality of life.2 The high efficacy of TKIs means that they are prescribed for long periods (years in most cases), which can compromise adherence and therefore the therapeutic success of this type of drug.

Therapeutic nonadherence is now recognised as a global public health problem with negative consequences for both patients and healthcare systems, as it is one of the main causes of therapeutic failure. In recent years, nonadherence has been exacerbated by the increase in the number of individuals with chronic diseases, those taking multiple medications, and the increase in life expectancy.3

Therapeutic nonadherence often goes unnoticed by the patient's clinical team, limiting the effectiveness of treatment.3 Therefore, it is necessary to assess the areas in which interventions can be made so that once the factors that have the greatest impact on adherence have been identified, a set of strategies and recommendations can be developed in an individualised manner to improve the patient's adherence. Within multidisciplinary teams in hospitals, pharmacists are healthcare professionals with very close contact with patients and can play a fundamental role in assessing the degree of adherence to treatment and establishing the appropriate interventions to improve it.

The aim of this study was to analyse the adherence of CML patients to TKI treatment and to assess the impact of pharmaceutical care (PC) on adherence. We also compared the differences in results according to the degree of specialisation of the pharmacist in charge of the outpatient units (OPUs).

A total of 130 patients participated in this study; 55.4% (n = 72) were men. Mean age was 58.9 years (range 20–90 years), and mean duration of TKI treatment was 4.7 years (0.6–13 years).

Adherence in this patient population was 68.4% (n = 89). When the patients were stratified according to the degree of therapeutic adherence, it was found that 56.9% (n = 74) had high adherence, 11.5% (n = 15) medium adherence, and 31.5% (n = 41) were nonadherent (Fig. 1).

Figure 1.

Stratification of study patients according to degree of adherence.

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At the time of the study, 63.1% (n = 82) of patients were being treated with imatinib, 25.4% (n = 33) with nilotinib, and 11.5% (n = 15) with dasatinib. It was found that adherence did not vary according to the drug used: imatinib (54.8%), nilotinib (63.6%), and dasatinib (54.3%) (P = .67).

During the second stage, 7 patients (5.38%) were lost to follow-up, leaving a final total of 123 participants: 55.4% male, mean age 58.9 years (20–90 years), mean duration of treatment 5.5 years (0.6–13 years). Of the 5 hospitals participating in this study, 3 had dedicated oncohaematology OPUs and 2 had general OPUs, which were attended by all patients receiving hospital-dispensed treatment, regardless of disease type. The baseline characteristics of the populations included in both groups were found to be homogeneous (Table 1).

After 8 months of pharmaceutical intervention, a significant improvement in adherence was observed (Fig. 2).

Figure 2.

Impact of the pharmaceutical intervention on adherence in the study population, showing the percentage of adherence at baseline and after 8 months of pharmaceutical care.

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Analysis of improvement in adherence by type of OPU after the pharmaceutical intervention showed a significant improvement in the adherence rate of patients attending dedicated oncohaematology OPUs (P < .001) (Fig. 3). However, the degree of adherence remained unchanged in patients who collected their medications from general OPUs (Fig. 3).

Figure 3.

Impact of outpatient units on improving adherence, showing the percentage of adherence at baseline and after 8 months of pharmaceutical care in dedicated oncohaematology outpatient units and general outpatient units.

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Oral antineoplastic drugs have given patients a degree of autonomy and quality of life that other treatments cannot match. However, a disadvantage is that patients may not adhere to them, which can reduce their effectiveness.5,6 Therapeutic nonadherence is currently considered one of the most important public health problems affecting both patients and healthcare systems. It is recognised as one of the most relevant factors affecting pharmacological effectiveness and safety, reducing patient quality of life, increasing morbidity and mortality, and increasing the use and cost of healthcare resources.3

Therapeutic adherence has been studied extensively in different healthcare fields. However, in the field of oncohaematology, the available data on adherence to oral therapy are scarce. In theory, cancer patients would be expected to be highly adherent due to the perceived seriousness of their disease. However, adherence to oral antineoplastic treatment can range from 16% to 100%, depending on the type of therapy and the method used to determine it.7 A study of a large cohort of CML patients on TKIs found that only 49% had high adherence.8 This study also assessed the clinical impact of therapeutic adherence in this patient population, finding that participants with high adherence had better overall survival than those with low or moderate adherence.8 On the other hand, a study of breast cancer patients receiving anastrozole as adjuvant treatment found that therapeutic adherence decreased over time.9 During the first year of therapy, around 75% of patients achieved optimal adherence, which decreased to around 60% from the third year onwards.9 Similarly, our study shows that with an average treatment duration of approximately 5 years, the proportion of individuals with high adherence was 56.9%, which was in principle independent of the TKI used (imatinib [54.8%], nilotinib [63.6%], and dasatinib [54.3%]) (P = .67).

We analysed adherence to TKIs in CML and determined the impact of PC on improving therapeutic adherence. The first step was to assess each participant's degree of adherence at the time of inclusion, which allowed us to identify individuals with low and moderate therapeutic adherence, and thus candidates for a more in-depth pharmaceutical intervention. Over a period of 8 months, each of these patients was monitored more closely for therapeutic adherence, with both verbal and written information reinforced and tailored to their individual characteristics. The importance of individualising PC in this way is to ensure that patients are able to internalise their own therapeutic plan in their daily lives. In a previous study, we found that certain socioeconomic characteristics of patients, such as their educational level and employment status, had a significant impact on adherence to TKIs. For this reason, it was essential to take these factors into account when developing corrective measures for therapeutic adherence.10

In the second stage, we aimed to validate the role of pharmacists in encouraging correct therapeutic adherence through appropriate PC. To this end, healthcare professionals must provide patients with the necessary information and make them aware of all aspects of their condition and medication, thus promoting continuity of treatment and ensuring its effectiveness and safety. Given this need, pharmacists play a fundamental role in assessing adherence and in implementing measures to optimise and maintain it. However, to date, no single intervention has been found to improve adherence globally in all patients and for all diseases.11 Therefore, given the diversity of factors that influence adherence, a multifactorial approach is required to improve it, as well as the use of multiple combined strategies implemented by the OPUs. In our case, we designed a specific PC plan (see Annex 1) to improve therapeutic adherence, mainly based on 2 types of interventions: behavioural strategies and educational strategies.

We used behavioural interventions to change or reinforce patients' attitudes, thereby increasing their involvement in self-care and in solving their problems. These strategies included reminder systems such as pill boxes, calendars, and electronic devices. On the other hand, motivational clinical interviewing is one of the most valuable tools available to health professionals to promote behavioural change in patients. This strategy not only improves the professional-patient relationship but also allows us to obtain accurate information about the individuals and identify the barriers to proper adherence. As educational interventions are mainly based on the provision of verbal and written information, we designed a patient information leaflet containing the essential aspects that individuals need to know about their treatment, which could be easily adapted to each participant's therapeutic plan. In addition, the contents of this leaflet were discussed and reviewed with the patients during their visits to the OPUs.

This study is the first to show that PC improves adherence outcomes in CML patients on TKI treatment. However, as our data show, although general OPUs applied the same measures as dedicated oncohaematology OPUs, only the latter achieved a percentage increase in adherence, highlighting the need for specialised clinical work with professionals trained in the disease. It is well known that a targeted, specific, and deliberate intervention is required to improve adherence. Over the last decade, this understanding has formed the basis of one of the most ambitious projects of the Spanish Society of Hospital Pharmacy (SEFH): the Strategic Map of Pharmaceutical Care for Outpatients (MAPEX).12 Thanks to this project, a set of models for stratifying patient care, documents on integration into multidisciplinary teams, and clinical practice guidelines for PC adapted to different diseases have been developed.12 This new PC model offers more targeted care and can help improve clinical outcomes and quality of life for individuals, while promoting maximum efficiency for the healthcare system. One of the key requirements of this model is that pharmacists must be highly specialised in each type of disease. However, we still have a long way to go in this regard, as there are still pharmacy services that do not have dedicated oncohaematology services.

This study may be limited by the inherent bias of this type of study: patients who are assessed repeatedly over time learn to respond in “right” way to the aspects that are being assessed, so the results obtained may be overestimated. However, to reduce such bias, adherence was determined by combining 2 measures: the ESPA scale and the record of medication dispensed by OPUs. However, although the ESPA scale was easily applicable to the CML patients on TKIs, it was originally validated to assess adherence to antiretroviral therapy in HIV patients, so we had no previous experience of its use in other types of population.4

Nevertheless, to the best of our knowledge, this is the first prospective interventional study to demonstrate how PC affects adherence to TKIs in CML patients. Given that adherence is one of the most important factors in the effectiveness of chronic treatments, our study offers several key insights that can help improve health outcomes by actively enhancing adherence in patients treated with oral antineoplastic drugs. Thus, the results show that dedicated oncohaematology OPUs provide more effective and higher quality PC, while offering better adaptation to the needs of individuals, which ultimately translates into better adherence outcomes for our patients.

Although therapeutic adherence has been studied extensively in various healthcare settings, this has not been the case in oncohaematology. We analysed adherence to tyrosine kinase inhibitors in patients with chronic myeloid leukaemia, while also assessing the impact of pharmaceutical care on adherence. Our results not only highlight the importance of pharmacists in the management of chronic treatment but also help to lay the groundwork for the implementation of more specific pharmaceutical care programmes, thus improving the health outcomes of oncohaematology patients.

This study shows that dedicated oncohaematology outpatient units provide more effective and higher quality pharmaceutical care, while offering better adaptation to the needs of individuals, which ultimately translates into better therapeutic adherence outcomes for our patients. To the best of our knowledge, this is the first prospective interventional study to demonstrate how pharmaceutical care affects adherence to tyrosine kinase inhibitors in patients with chronic myeloid leukaemia.

In order to guarantee confidentiality, the participants' data were anonymised, thus ensuring that the participants could not be identified. All patients received an information sheet and signed an informed consent form to participate in the study.

This study was approved by each of the clinical research ethics committees of the participating hospitals (code LOH-IMA-2013-01).

All of the authors of this study contributed significantly to its preparation. Study design: Betel Del Rosario, María Micaela Viña Romero, Virginia González Rosa, Carolina Alarcón Payer, Leonor Oliva Oliva, Gloria Julia Nazco Casariego, Fernando Gutiérrez Nicolás.

Literature search: Betel Del Rosario, María Micaela Viña Romero, Virginia González Rosa, Carolina Alarcón Payer, Leonor Oliva Oliva.

Data collection and statistical analysis: Betel Del Rosario, Virginia González Rosa, Carolina Alarcón Payer, Fernando Gutiérrez Nicolás.

Manuscript preparation: Betel Del Rosario, María Micaela Viña Romero, Virginia González Rosa, Carolina Alarcón Payer, Leonor Oliva Oliva, Gloria Julia Nazco Casariego, Fernando Gutiérrez Nicolás.

All authors accept the responsibilities defined by the International Committee of Medical Journal Editors (available at: http://www.icmje.org/). In the event of publication, the authors grant exclusive rights of reproduction, distribution, translation, and public communication (by any means or medium, whether sound, audiovisual or electronic support) of their work to Farmacia Hospitalaria and, by extension, to the SEFH.

For this purpose, a letter of assignment of rights will be signed at the time of submitting the work through the online manuscript management system.

Betel Del Rosario García: Writing – review & editing, Writing – original draft, Validation, Supervision, Methodology, Investigation, Formal analysis, Data curation, Conceptualization. María Micaela Viña Romero: Visualization, Supervision, Methodology, Investigation, Data curation, Conceptualization. Virginia González Rosa: Validation, Methodology, Investigation, Formal analysis, Data curation. Carolina Alarcón Payer: Validation, Supervision, Methodology, Investigation, Formal analysis, Data curation. Leonor Oliva Oliva: Validation, Supervision, Methodology, Investigation, Formal analysis, Data curation. Gloria Julia Nazco Casariego: Validation, Supervision, Investigation, Formal analysis. Fernando Gutiérrez Nicolás: Visualization, Validation, Supervision, Methodology, Investigation, Formal analysis, Data curation, Conceptualization.

None declared.