Response and Adherence to Nilotinib in Daily practice (RAND study): an in-depth observational study of chronic myeloid leukemia patients treated with nilotinib.

Autor: Boons CCLM; Department of Clinical Pharmacology and Pharmacy, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Centre Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. c.boons@amsterdamumc.nl.; Amsterdam Public Health Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands. c.boons@amsterdamumc.nl., Timmers L; Department of Clinical Pharmacology and Pharmacy, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Centre Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.; Amsterdam Public Health Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands., Janssen JJWM; Department of Hematology, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Centre Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands., Westerweel PE; Department of Hematology, Albert Schweitzer Ziekenhuis, Albert Schweitzerplaats 25, 3318 AT, Dordrecht, The Netherlands., Blijlevens NMA; Department of Hematology, Radboudumc, Geert Grooteplein Zuid 10, 6525 GA, Nijmegen, The Netherlands., Smit WM; Department of Hematology, Medisch Spectrum Twente, Koningsplein 1, 7512 KZ, Enschede, The Netherlands., Bartelink IH; Department of Clinical Pharmacology and Pharmacy, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Centre Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands., Wilschut JA; Amsterdam Public Health Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands., Swart EL; Department of Clinical Pharmacology and Pharmacy, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Centre Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands., Hendrikse NH; Department of Clinical Pharmacology and Pharmacy, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Centre Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.; Department of Radiology and Nuclear Medicine, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Centre Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands., Hugtenburg JG; Department of Clinical Pharmacology and Pharmacy, Amsterdam UMC, Vrije Universiteit Amsterdam, Cancer Centre Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.; Amsterdam Public Health Research Institute, Amsterdam UMC, Vrije Universiteit Amsterdam, De Boelelaan 1117, 1081 HV, Amsterdam, The Netherlands.
Jazyk: angličtina
Zdroj: European journal of clinical pharmacology [Eur J Clin Pharmacol] 2020 Sep; Vol. 76 (9), pp. 1213-1226. Date of Electronic Publication: 2020 Jun 02.
DOI: 10.1007/s00228-020-02910-3
Abstrakt: Introduction: This comprehensive observational study aimed to gain insight into adherence to nilotinib and the effect of (non)adherence on exposure (C min ) and treatment outcomes.
Methods: Chronic myeloid leukemia (CML) patients using nilotinib were followed for 12 months. Adherence was measured by Medication Event Monitoring System (MEMS), pill count, and Medication Adherence Report Scale (MARS-5). Nilotinib C min and patient-reported outcomes (i.e., quality of life, side effects, beliefs, satisfaction) were measured at baseline, 3, 6, and 12 months.
Results: Sixty-eight patients (57.5 ± 15.0 years, 49% female) participated. Median adherence to nilotinib (MEMS and pill count) was ≥ 99% and adherence < 90% was rare. Self-reported nonadherence (MARS-5) increased in the first year of treatment to a third of patients. In line with the strong beliefs in the necessity of taking nilotinib, forgetting to take a dose was more prevalent than intentionally adjusting/skipping doses. Nilotinib C min were generally above the therapeutic target in 95% of patients. Patients reported a variety of side effects, of which fatigue was most frequent. The mean C min was higher in patients who reported severe itching and fatigue. The overall 1-year MMR rate ranged from 47 to 71%.
Conclusion: Substantial nonadherence (< 90%) to nilotinib was rare and nilotinib C min were generally above the therapeutic target. Lack of response in our group of patients was not related to nonadherence or inadequate C min . Nevertheless, a considerable number of patients experienced difficulties in adhering to the twice daily fasted dosing regimen, emphasizing the importance of continuous support of medication adherence in CML.
Clinical Trial Registration: NTR3992 (Netherlands Trial Register, www.trialregister.nl ).
Databáze: MEDLINE
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