Retrospective real-world comparison of clinical and economic burden between first-generation and second-generation tyrosine kinase inhibitors (TKIs) in chronic myeloid leukemia (CML).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e19030-e19030
Author(s):  
T. Alexander Smith ◽  
Sumit Verma ◽  
Yi Liu ◽  
Slaven Sikirica ◽  
Nora Anita Janjan

e19030 Background: TKIs are the standard of care for the treatment of chronic phase CML under National Comprehensive Cancer Network (NCCN) guidelines. Imatinib is recommended as a first-generation TKI (1GTKI), and bosutinib, dasatinib, nilotinib, and ponatinib are recommended as second-generation TKIs (2GTKIs). TKIs are associated with high healthcare resource utilization (HRU) and costs, although literature is limited comparing 1GTKI and 2GTKIs in a U.S. population. Methods: Using the Veteran’s Health Administration (VHA) database between April 1, 2013 and March 31, 2018, the study included patients aged ≥18 years with ≥1 medical claim for CML and ≥1 prescription claim for a TKI on or after the initial CML diagnosis date during the identification period (October 1, 2014 to September 30, 2017); the first TKI prescription claim was defined as the index date. Inverse probability of treatment weighting (IPTW) minimized potential confounding; included variables were age, race, Quan-Charlson Comorbidity Index (CCI) score, and CHA2DS2-VASc Score. Medication possession ratio (MPR) assessed adherence to index TKI; optimal adherence was defined as MPR ≥80%. Results: 944 patients were included: 78.9% on 1GTKI and 21.1% on 2GTKI. Mean age was 62.21 years (SD:18.8); 77.2% were white. At baselinetients on 1GTKI had a higher comorbidity burden than 2GTKIs: COPD (19.7% vs. 8%; p < 0.01), anemia (17.7% vs. 11.1%; p = 0.02), GI symptoms (28.5% vs. 18.6%; p < 0.01), cardiac dysrhythmias (15.6% vs. 7.5%; p < 0.01), coronary artery disease (26.3% vs. 13.6%; p < 0.01), hypertension (55.7% vs. 43.2%; p < 0.01) and CHA2DS2-VASc Score (2.2 vs 1.6; p < 0.01). Optimal adherence was higher with 1GTKI (69.6% vs. 62.2%; p = 0.04), although this was not statistically significant when mean MPR was compared. During follow-up, no difference between 1GTKI and 2GTKIs patients occurred with cardiac-related risk factors or CHA2DS2-VASc Score. Compared to 1GTKI, 2GTKIs had lower medical (inpatient and outpatient) costs ($3,162 vs. $3,906; p = 0.04) but higher all-cause pharmacy cost ($7,214 vs. $3,895; p < 0.01) due to imatinib becoming a generic drug during the study period. CML-related ($2,260 vs. $1,640, p < 0.01) and cardiac-related medical costs ($1,365 vs. $665, p < 0.01) were significantly higher in 1GTKI vs. 2GTKIs patients. Conclusions: Adherence to TKI therapy was suboptimal for both 1GTKI and 2GTKIs. 2GTKIs incurred lower medical cost in comparison to 1GTKI. Differences in total all-cause cost was primarily driven by pharmacy cost of TKIs. These results show that, beyond the cost of the TKI, using a 2GTKIs in the first-line can lead to cost offsets when compared to imatinib.

Hematology ◽  
2020 ◽  
Vol 2020 (1) ◽  
pp. 228-236
Author(s):  
Vivian G. Oehler

Abstract In 2020, for the great majority of patients with chronic phase chronic myeloid leukemia (CML), life expectancy is unaffected by a diagnosis of CML because of the unparalleled efficacy of ABL-targeted tyrosine kinase inhibitors (TKIs) in halting disease progression. A wealth of choices exist for first-line treatment selection, including the first-generation TKI imatinib and the second-generation TKIs bosutinib, dasatinib, and nilotinib. How I select first-line therapy between first-generation and second-generation TKIs is discussed in the context of patient-specific CML disease risk, therapy-related risks, and treatment goals. Although rare, identifying patients with CML at higher risk for disease progression or resistance is important and influences first-line TKI selection. I review the impact of first-generation vs second-generation TKI selection on treatment response and outcomes; the ability to achieve, as well as the timing of, treatment-free remission; and the impact of specific TKIs on longer-term health.


2016 ◽  
Vol 1 (1) ◽  
pp. 105-118
Author(s):  
Anita Pugliese ◽  
Julie Ray ◽  
Neli Esipova

This paper reports the results from Gallup’s global analysis of the likelihood of first-generation migrants, second-generation migrants and the native-born to send financial help in the form of money or goods to others inside or outside their respective country of residence. The findings in this paper are based on more than 450,000 interviews conducted through Gallup’s World Poll in 157 countries in 2012, 2013 and 2014. The sample includes more than 26,000 first-generation migrants and more than 20,000 second-generation migrants. The large sample enables Gallup to analyze first-generation migrants by the duration of their stay in their adopted country and compare their remittance behaviors with second-generation migrants and the native-born.


Author(s):  
Asaad Abdullwahab AbdulKarim ◽  
Waleed Massaher Hamad ◽  
Salah Ibrahim Hamadi

Abstract     The Frankfurt School is characterized by its critical nature and it is the result of the Marxist socialist thought as it contributed to the development of the German thought in particular and the Western thought in general through important ideas put forward by a number of pioneers in the various generations of the school and most notably through the leading pioneer in the first generation, Marcuse, and the leading pioneer of the second  generation, Habermas, whose political ideas had an important impact on global thinking and later became the basis of the attic of many critical ideas. In spite of the belief of the school members in the idea of the criticism of power and community, each had his own ideas that distinguish him from the others.


2020 ◽  
Vol 25 (1) ◽  
pp. 23-32
Author(s):  
Gerd Laux

Für die Therapie schizophrener Erkrankungen sind seit fast 60 Jahren Antipsychotika/Neuroleptika aufgrund ihrer antipsychotischen Wirkung von zentraler Bedeutung. Die Einteilung kann unter verschiedenen Gesichtspunkten erfolgen (chemische Struktur, neuroleptische Potenz, Rezeptorprofil), heute werden üblicherweise unterschieden typische (traditionelle, klassische, konventionelle) Antipsychotika der ersten Generation ‒ »First Generation Antipsychotics« (FGA) ‒ und sog. atypische (»neuere«) Neuroleptika bzw. Antipsychotika der zweiten Generation ‒»Second Generation Antipsychotics« (SGA). Hierzu zählen Aripiprazol, Asenapin, Cariprazin, Clozapin, Olanzapin, Quetiapin, Risperidon, Sertindol und Ziprasidon. Hierbei handelt es sich um keine homogene Gruppe – sowohl neuropharmakologisch (Wirkmechanismus), als auch hinsichtlich klinischem Wirkprofil und dem Nebenwirkungsspektrum bestehen z. T. erhebliche Unterschiede. Neben der Akut-Medikation ist eine Langzeitmedikation bzw. Rezidivprophylaxe mit Antipsychotika für die Rehabilitation vieler schizophrener Patienten im Sinne eines »Stresspuffers« von grundlegender Bedeutung. In Placebo-kontrollierten Studien trat bei Patienten, die über ein Jahr behandelt wurden, bei etwa 30% unter Neuroleptika ein Rezidiv auf, unter Placebo bei mehr als 70%. Für die Langzeitbehandlung bietet sich der Einsatz von Depot-Neuroleptika an, neu entwickelt wurden Langzeit-Depot-Injektionen mit Intervallen von bis zu 3 Monaten. Grundsätzlich ist die niedrigstmögliche (wirksame) Dosis zu verwenden. Im Zentrum der Nebenwirkungen (UAW) standen lange Zeit extrapyramidal-motorische Bewegungsstörungen (EPMS), mit der Einführung von Clozapin und anderen atypischen Antipsychotika der zweiten Generation gewannen andere Nebenwirkungen an Bedeutung. Hierzu zählen Gewichtszunahme, Störungen metabolischer Parameter und ein erhöhtes Risiko für Mortalität und zerebrovaskuläre Ereignisse bei älteren Patienten mit Demenz. Entsprechende Kontrolluntersuchungen sind erforderlich, für Clozapin gibt es aufgrund seines Agranulozytose-Risikos Sonderbestimmungen. Immer sollte ein Gesamtbehandlungsplan orientiert an der neuen S3-Praxisleitlinie Schizophrenie der DGPPN aufgestellt werden, der psychologische und milieu-/sozial-therapeutische Maßnahmen einschließt. Standard ist heute auch eine sog. Psychoedukation, für Psychopharmaka liegen bewährte Patienten-Ratgeber vor.


Author(s):  
Elisabeth Schimpfössl

Chapter 7 focuses on the upbringing of the second generation of the Russian bourgeoisie. As the first generation of wealthy Russians grows older, they are becoming more aware of their own mortality and are preparing to hand over their wealth to the next generation. It seems that rich Russians are yet to find a convincing narrative to justify their children’s legitimate entitlement to wealth that does not contradict their own everyday ideology of being self-made. Nevertheless, a two-pronged approach is emerging. First, in line with the shift toward new modesty, children are being encouraged to cultivate a habitus of privilege, as Sherman suggests in the case with wealthy US Americans, which makes them appear morally worthy in an environment marked by extreme inequality. Second, via their philanthropy the rich are supporting institutions and scholars in an effort to strengthen a dynamic capitalist environment in which privileged status is respected.


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