Use patterns of first-line inhibitors of tyrosine kinase and time to change to second-line therapy in chronic myeloid leukemia

Abstract

Background Chronic myeloid leukemia (CML) has a low incidence but a high burden of disease, and is treated with high-cost tyrosine kinase inhibitors (TKI). Objective To determine the time from the start of a first-line TKI until it passes to second-line, and to establish the reasons for the change of therapy time. Setting Patients with Philadelphia-positive CML treated with some TKI. Methods Retrospective cohort study, between January 1 2007 and July 31 2015, with information obtained from medical records, the time to change initial drugs to secondline therapy, and the reasons for change, were identified. Kaplan-Meier survival analysis was carried out. Main outcome measure A change in therapy to the secondline TKI and the final reason for the change of therapy. Results A total of 247 patients treated were found in 22 cities in Colombia with a mean age of 53.2 ± 15.2 years. The drug most used as initial therapy was imatinib; 53.8% of cases had to change to another TKI. 50% of patients changed therapy in 42 months, men in 24 and women in 67 months (95% CI 14.314-33.686; p = 0.001). Being male (OR 2.23; 95% CI 1.291-3.854; p = 0.004) and receiving hydroxyurea (OR 3.65; 95% CI 1.601-8.326; p = 0.002) were associated with a higher probability of switching to nilotinib or dasatinib, while receiving a new-generation TKI (OR 0.15; 95% CI 0.071-0.341; p < 0.001) reduced this risk. Conclusions A high proportion of patients needed to change to a second line with nilotinib and dasatinib management. It is necessary to obtain more real world evidence, to improve the effectiveness, adherence and safety of the treatment.

Pattern of Use and Long-Term Safety of Tyrosine Kinase Inhibitors: A Decade of Real-World Management of Chronic Myeloid Leukemia

“…In fact, the median duration of treatment was 1 year shorter for nilotinib compared with imatinib, although there was no statistical significance (4.55 years [IQR 1.39-7.89] vs. 3.59 years [IQR 2.23-4.76], p = 0.402). Nevertheless, two recent national and international observational studies by Castagnetti et al and Machado-Alba and Machado-Duque [24,25] found similar results, reporting a significantly higher proportion of switches in patients treated with imatinib compared with second-generation TKIs, mainly due to resistance. On the other hand, in our study most switches from imatinib were due to severe treatment intolerance.…”

Evaluation of real-world versus clinical trial outcomes of tyrosine kinase inhibitor therapy for chronic myeloid leukemia

“…A total of seven studies met inclusion criteria and evaluated the safety of TKIs in real-world patients. 7 , 10 , 11 , 13 , 19 , 21 , 22 Five landmark phase II or III clinical trials were analyzed for safety outcomes. 4 – 6 , 15 , 17 …”

“…A total of seven studies met inclusion criteria and evaluated the safety of TKIs in real-world patients. 7,10,11,13,19,21,22 Five landmark phase II or III clinical trials were analyzed for safety outcomes. [4][5][6]15,17 Changes and discontinuations of TKI therapy were the most commonly reported measures of safety and tolerability in real-world studies.…”

Availability of secondary healthcare data for conducting pharmacoepidemiology studies in Colombia: A systematic review

“…Among these, 351 articles were excluded after title screening and the abstract of the 784 remaining papers was assessed. Finally, 461 publications were excluded following the eligibility criteria and thus, 323 articles that had interpretable data and fulfilled the eligibility criteria were used for data extraction…”

“…A pharmacy dispensing company (Audifarma SA) was identified in the SLR as the most commonly used database for RWE 34,42,61,63,72,73,94‐98,100‐109,111‐115,117,118,120,122‐131,134‐141,163,168,242,301,310 . It contains demographic data, diagnosis by ICD‐10, and drug dispensation records coded by the Anatomical Therapeutic Chemical (ATC) classification, which can be used to identify comorbidities, drug‐to‐drug interactions, medication errors, adverse events, and calculate adherence rates.…”