Keywords
Leukemia Myelogenous Chronic BCR-ABL Positive
Risk Factors
How to Cite
Abstract
Objective: To determine the prevalence of non-adherence, associated causes, the proportion of patients who improve this non-compliance, and its explanatory variables. Methods: A retrospective observational cross-sectional analytical study was performed, on patients with Chronic Myeloid Leukemia and treatment with Imatinib generic brand, dispensed by a health institution between August 2018 and December 2022. Drug adherence status was defined as the dependent variable and sociodemographic, clinical, and pharmacological variables as independent variables. The information was extracted from a database of pharmacotherapeutic follow-ups performed on patients automatically identified through algorithms as non-adherent. Pharmacists contacted the patient to intervene and improve this compliance. Univariate, bivariate, and multivariate analysis was performed. Results: A total of 315 patients were analyzed, with a mean age of 52±17 years, median treatment time of 250 days [RIC 97-362], 11% were polymedicated and 16.8% were multimorbid; 30.5% were non-adherent. The associated causes were lack of specialist appointment (39.6%), delay in authorization by the insurer (31.9%) and not having a current medical prescription (5.5%). Of the non-adherent patients, 86% had a history of pharmacological non-adherence and 61% of non-timely claims. After the pharmacist's intervention, 80% improved this inadequate compliance. During the bivariate analysis, the variables age, time on treatment, and having a history of non-adherence were found to be significant, which, in the multivariate model, behaved as risks with statistical significance. When adjusting the model for the other variables, although they continued to behave as risks, only the variable of a history of non-adherence remained statistically significant. Conclusion: The prevalence of non-adherence is higher than that reported in the literature, the associated causes are mainly administrative, and the persons at greater risk of presenting this health outcome are those with greater age, less time in treatment, and those with a history of non-adherence to other medications.
References
González AR. Leucemia mieloide crónica, paradigma de tratamiento en Oncohematología. Rev Cuba Hematol Inmunol Hemoterapia. 2020; 36(3).
Meza-Espinoza JP, González-García JR, Contreras-Gutiérrez JA, Picos-Cárdenas VJ. Leucemia mieloide crónica: Un artículo de divulgación científica. REVMEDUAS. 2022; 12: 257–271. doi: https://doi.org/10.28960/revmeduas.2007-8013.v12.n3.010
Phuar HL, Begley CE, Chan W, Krause TM. Tyrosine kinase inhibitors and the relationship with adherence, costs, and health care utilization in commercially insured patients with newly diagnosed chronic myeloid leukemia. Am J Clin Oncol. 2020; 43: 517–525. doi: https://doi.org/10.1097/COC.0000000000000700
Alves AR, Lima WG, Nagai MM, Rodrigues JPV, Ayres LR. Adherence and/or discontinuation of imatinib mesylate in patients with chronic myeloid leukemia. Brazilian J Pharm Sci. 2016; 52(4): 581–589. doi: https://doi.org/10.1590/s1984-82502016000400001
Deininger MW, Shah NP, Altman JK, Berman E, Bhatia R, Bhatnagar B, et al. Chronic myeloid leukemia, version 2.2021, NCCN clinical practice guidelines in oncology. J Natl Compr Can Netw. 2020; 18(10): 1385–1415. doi: https://doi.org/10.6004/jnccn.2020.0047
Poudel G, Tolland MG, Hughes TP, Pagani IS. Mechanisms of resistance and implications for treatment strategies in chronic myeloid leukaemia. Cancers (Basel). 2022; 14(14): 3300. doi: https://doi.org/10.3390/cancers14143300
Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin. 2022; 72(1): 7–33. doi: https://doi.org/10.3322/caac.21708
Maas CCHM, van Klaveren D, Ector GICG, Posthuma EFM, Visser O, Westerweel PE, et al. The evolution of the loss of life expectancy in patients with chronic myeloid leukaemia: a population‐based study in the Netherlands, 1989–2018. Br J Haematol. 2022; 196(5): 1219–1224. doi: https://doi.org/10.1111/bjh.17989
Yu L, Wang H, Gale RP, Qin Y, Lai Y, Shi H, et al. Impact of socio-demographic co-variates on prognosis, tyrosine kinase-inhibitor use and outcomes in persons with newly-diagnosed chronic myeloid leukaemia. J Cancer Res Clin Oncol. 2022; 148: 449–459. doi: https://doi.org/10.1007/s00432-021-03624-4
Breccia M, Efficace F, Colafigli G, Scalzulli E, Di Prima A, Martelli M, et al. Tyrosine kinase inhibitor discontinuation in the management of chronic myeloid leukemia: a critical review of the current practice. Expert Rev Hematol. 2020; 13: 1311–13|8. doi: https://doi.org/10.1080/17474086.2021.1852924
Corral Alaejos Á, Zarzuelo Castañeda A, Jiménez Cabrera S, Sánchez‐Guijo F, Otero MJ, Pérez‐Blanco JS. External evaluation of population pharmacokinetic models of imatinib in adults diagnosed with chronic myeloid leukaemia. Br J Clin Pharmacol. 2022; 88: 1913–1924. doi: https://doi.org/10.1111/bcp.15122
Noens L, van Lierde M-A, De Bock R, Verhoef G, Zachée P, Berneman Z, et al. Prevalence, determinants, and outcomes of nonadherence to imatinib therapy in patients with chronic myeloid leukemia: the ADAGIO study. Blood. 2009; 113: 5401–5411. doi: https://doi.org/10.1182/blood-2008-12-196543
Heiney SP, Sorrell M, Sheng J, Adams SA, Nelson K, Nguyen LA, et al. Interventions to Improve Adherence to Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia. Am J Clin Oncol. 2021; 44: 291–298. doi: https://doi.org/10.1097/COC.0000000000000818
Klil-Drori AJ, Yin H, Azoulay L, Harnois M, Gratton M-O, Busque L, et al. Adherence with generic imatinib for chronic myeloid leukemia: a matched cohort study. Haematologica. 2019; 104: e293–295. doi: https://doi.org/10.3324/haematol.2018.211235
Suárez-Artime P, Durán-Piñeiro G, Rodríguez-Cobos M, Rojo-Valdés JM, Martínez-Bahamonde FJ, Zarra-Ferro I. Medication adherence to obeticholic acid: a real-world experience using medication event monitoring systems. Farm Hosp. 2022; 46: 260–264.
Schneider MP, Achtari Jeanneret L, Chevaux B, Backes C, Wagner AD, Bugnon O, et al. A Novel approach to better characterize medication adherence in oral anticancer treatments. Front Pharmacol. 2019; 9. doi: https://doi.org/10.3389/fphar.2018.01567
Lima PRG, Gonçalves GMS, Rodrigues RCM, Oliveira-Kumakura AR de S. Factors related to patient adherence to the use of new oral anticoagulants. Rev Esc Enferm USP. 2022; 56. doi: https://doi.org/10.1590/1980-220x-reeusp-2021-0191
Signorelli J, Bell C, Monaco S. Oral oncolytic monitoring pilot with patient-reported outcomes and adherence assessments. Journal of Oncology Pharmacy Practice. 2022: 107815522211126. doi: https://doi.org/10.1177/10781552221112603
Reis SRC dos, Quixadá AT de S, Nunes ST, Cid DMC, Souza JH de, Costa CMBE da, et al. Adherence to treatment with imatinib in chronic myeloid leukemia: a study of the first decade of responses obtained at a Brazilian hospital. Rev Bras Hematol Hemoter. 2013; 35: 174. doi: https://doi.org/10.5581/1516-8484.20130053
Kim Y, Go T-H, Jang J, Lee JB, Lim ST, Shim KY, et al. Survival impact of adherence to tyrosine kinase inhibitor in chronic myeloid leukemia. Korean J Intern Med. 2021; 36: 1450–8. doi: https://doi.org/10.3904/kjim.2021.158
Anderson KR, Chambers CR, Lam N, Yau PS, Cusano F, Savoie ML, et al. Medication adherence among adults prescribed imatinib, dasatinib, or nilotinib for the treatment of chronic myeloid leukemia. J Oncol Pharm Pract. 2015; 21: 19–25. doi: https://doi.org/10.1177/1078155213520261
Kapoor J, Agrawal N, Ahmad R, Sharma SK, Gupta A, Bhurani D. Factors influencing adherence to imatinib in Indian chronic myeloid leukemia patients: a cross-sectional study. Mediterr J Hematol Infect Dis. 2015; 7: e2015013. doi: https://doi.org/10.4084/mjhid.2015.013
Verbrugghe M, Duprez V, Beeckman D, Grypdonck M, Quaghebeur M, Verschueren C, et al. Factors Influencing Adherence in Cancer Patients Taking Oral Tyrosine Kinase Inhibitors. Cancer Nurs. 2016; 39: 153–162. doi: https://doi.org/10.1097/NCC.0000000000000250
Noens L, Hensen M, Kucmin-Bemelmans I, Lofgren C, Gilloteau I, Vrijens B. Measurement of adherence to BCR-ABL inhibitor therapy in chronic myeloid leukemia: current situation and future challenges. Haematologica. 2014; 99: 437–47. doi: https://doi.org/10.3324/haematol.2012.082511
Chuah PL, Jamal NF, Siew CJ, Ahmad Bustamam RS, Jeyasingam V, Khong KC. Assessment of adherence to imatinib and health-related quality of life among patients with gastrointestinal stromal tumor: A cross-sectional study in an oncology clinic in Malaysia. Patient Prefer Adherence. 2021; 15: 2175–2184. doi: https://doi.org/10.2147/PPA.S310409
Ran P, Li J, Wu X, Yang H, Zhang J. Primary localized gastrointestinal stromal tumors: Medication adherence and prognosis according to gender. Patient Prefer Adherence. 2022; 16: 2077–2087. doi: https://doi.org/10.2147/PPA.S376843
Puigventós F, Riera M, Delibes C, Peñaranda M, Fuente L de la, Boronat A. Estudios de adherencia a los fármacos antirretrovirales. Una revisión sistemática. Med Clin (Barc). 2002; 119: 130–137. doi: https://doi.org/10.1016/S0025-7753(02)73341-1
Codina C, Martínez M, Tuset M, del Cacho E, Teresa Martín MM, Miró J, et al. Comparación de tres métodos de cálculo de adherencia en pacientes con tratamiento antirretroviral. Enferm Infecc Microbiol Clin. 2002; 20: 484–490. doi: https://doi.org/10.1016/S0213-005X(02)72850-4
Blaschke TF, Osterberg L, Vrijens B, Urquhart J. Adherence to Medications: Insights Arising from Studies on the Unreliable Link Between Prescribed and Actual Drug Dosing Histories. Annu Rev Pharmacol Toxicol. 2012; 52: 275–301. doi: https://doi.org/10.1146/annurev-pharmtox-011711-113247
Chatha ZF, Rashid U, Olsen S, Din F ud, Khan A, Nawaz K, et al. Pharmacist-led counselling intervention to improve antiretroviral drug adherence in Pakistan: a randomized controlled trial. BMC Infect Dis. 2020; 20: 874. doi: https://doi.org/10.1186/s12879-020-05571-w
Hovland R, Bremer S, Frigaard C, Henjum S, Faksvåg PK, Sæther EM, et al. Effect of a pharmacist-led intervention on adherence among patients with a first-time prescription for a cardiovascular medicine: a randomized controlled trial in Norwegian pharmacies. Int J Pharm Pract. 2020; 28: 337–345. doi: https://doi.org/10.1111/ijpp.12598
Burnier M, Egan BM. Adherence in Hypertension. Circ Res. 2019; 124: 1124–1240. doi: https://doi.org/10.1161/CIRCRESAHA.118.313220
Abou Dalle I, Kantarjian H, Burger J, Estrov Z, Ohanian M, Verstovsek S, et al. Efficacy and safety of generic imatinib after switching from original imatinib in patients treated for chronic myeloid leukemia in the United States. Cancer Med. 2019; 8: 6559–8565. doi: https://doi.org/10.1002/cam4.2545
Bonifacio M, Scaffidi L, Binotto G, Miggiano MC, Danini M, Minotto C, et al. Safety and efficacy of switching from branded to generic imatinib in chronic phase chronic myeloid leukemia patients treated in Italy. Leuk Res. 2018; 74: 75–79. doi: https://doi.org/10.1016/j.leukres.2018.09.018
Scalzulli E, Colafigli G, Latagliata R, Pepe S, Diverio D, Stocchi F, et al. Switch from branded to generic imatinib: impact on molecular responses and safety in chronic-phase chronic myeloid leukemia patients. Ann Hematol. 2020; 99: 2773–2777. doi: https://doi.org/10.1007/s00277-020-04096-1
Danthala M, Gundeti S, Kuruva SP, Puligundla KC, Adusumilli P, Karnam AP, et al. Generic Imatinib in Chronic Myeloid Leukemia: Survival of the Cheapest. Clin Lymphoma Myeloma Leuk. 2017; 17: 457–462. doi: https://doi.org/10.1016/j.clml.2017.05.006
Dou X, Qin Y, Lai Y, Shi H, Huang X, Jiang Q. Comparable efficacy, and safety of generic imatinib and branded imatinib in patients with newly diagnosed chronic myeloid leukemia with a consideration of socioeconomic characteristics: a retrospective study from a single center. Clin Lymphoma Myeloma Leuk. 2020; 20: e304–315. doi: https://doi.org/10.1016/j.clml.2020.01.009
Awidi A, Abbasi S, Alrabi K, Kheirallah KA. Generic imatinib therapy among Jordanians: An observational assessment of efficacy and safety in routine clinical practice. Clin Lymphoma Myeloma Leuk. 2017; 17: e55–61. doi: https://doi.org/10.1016/j.clml.2017.08.001
Trivedi D, Landsman-Blumberg P, Darkow T, Smith D, Mc DM, Daniel Mullins C. Adherence and persistence among chronic myeloid leukemia patients during second-line tyrosine kinase inhibitor treatment. J Manag Care Spec Pharm. 2014; 20: 1006–15. doi: https://doi.org/10.18553/JMCP.2014.20.10.1006
Feng W, Henk H, Thomas S, Baladi J, Hatfield A, Goldberg GA, et al. Compliance and persistency with imatinib. J Clin Oncol. 2006; 24: 6038–6038. doi: https://doi.org/10.1200/jco.2006.24.18_suppl.6038
Chang CS, Yang YH, Hsu CN, Lin MT. Trends in the treatment changes and medication adherence of chronic myeloid leukemia in Taiwan from 1997 to 2007: a longitudinal population database analysis. BMC Health Serv Res. 2012; 12: 359. doi: https://doi.org/10.1186/1472-6963-12-359
Cole AL, Jazowski SA, Dusetzina SB. Initiation of generic imatinib may improve medication adherence for patients with chronic myeloid leukemia. Pharmacoepidemiol Drug Saf. 2019; 28: 1529–1533. doi: https://doi.org/10.1002/pds.4893
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