Cost Effectiveness of CDK4/6 Inhibitors in the First-Line Treatment of HR+/HER2- Metastatic Breast Cancer in Postmenopausal Women in the USA.

BACKGROUND AND OBJECTIVE: Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors improve progression-free survival when combined with endocrine therapies in patients with hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer. However, the comparative cost effectiveness of utilizing three US Food and Drug Administration-approved CDK4/6 inhibitors is unknown. Therefore, we aimed to evaluate the cost effectiveness of individual CDK4/6 inhibitors (palbociclib, ribociclib, abemaciclib) with letrozole versus letrozole monotherapy in the first-line treatment of hormone receptor-positive/human epidermal growth factor receptor 2-negative metastatic breast cancer in the USA. METHODS: We constructed a Markov-based decision-analytic model to evaluate the cost effectiveness of CDK4/6 inhibitors plus endocrine therapies over a 40-year lifetime from a third-party payer perspective. The model incorporated health states (progression-free disease, progressive disease, and death), major adverse events (neutropenia), and cancer-specific and all-cause mortality. Using clinical efficacy and quality-of-life scores (utility) data from clinical trials, we estimated quality-adjusted life-years (QALYs) and incremental cost-effectiveness ratios using Medicare charges reported in US dollars per 2022 valuation and a discount rate of 3% applied to costs and outcomes. We performed deterministic and probabilistic sensitivity analyses to evaluate parametric and decision uncertainty. RESULTS: Compared to letrozole, the model estimated an increase of 5.72, 5.87, and 6.39 in QALYs and costs of $799,178, $788,168, and $741,102 in combining palbociclib, ribociclib, and abemaciclib plus letrozole, respectively. Palbociclib or ribociclib plus letrozole were dominated by abemaciclib plus letrozole. Compared with letrozole, abemaciclib plus letrozole resulted in an incremental cost-effectiveness ratio of $457,538 per QALY with an incremental cost of $553,621 and an incremental QALY gain of 1.21. The results were sensitive to the cost of abemaciclib, disease progression utility, and patients' age. CONCLUSIONS: At a willingness to pay of $100,000/QALY gained, our model predicts that combining CDK4/6 inhibitors plus letrozole is not cost effective with a marginal increase in QALYs at a high cost. Lowering the cost of these drugs or identifying patients who can receive maximal benefit from CDK4/6 inhibitors would improve the value of this regimen in patients.

Risk of Serious Adverse Events Associated With Individual Cholinesterase Inhibitors Use in Older Adults With Dementia: A Population-Based Cohort Study.

BACKGROUND AND OBJECTIVE: Cholinesterase inhibitors (ChEIs) are used as first-line pharmacotherapy to manage dementia. However, there are limited data regarding their relative safety. This study evaluated the risk of serious adverse events (SAEs) associated with individual ChEIs in older adults with dementia and also examined sex-based and dose-based effects on this risk. METHODS: This was a retrospective cohort study using 2013-2015 US Medicare claims data involving Parts A, B, and D. Patients aged ≥ 65 years with a dementia diagnosis and incident use of the ChEIs, namely donepezil, galantamine, or rivastigmine, were included. The primary outcome of interest was SAEs defined as emergency department visits, inpatient hospitalizations, or death within 6 months of ChEI initiation. Multivariable Cox proportional hazards regression with propensity score (PS) as a covariate and inverse probability of treatment weighting generated using generalized boosted models was used to assess the risk of SAEs across individual ChEIs. RESULTS: The study included 767,684 older adults with dementia who were incident new users of ChEIs (donepezil 79.42%, rivastigmine 17.67%, galantamine 2.91%). SAEs were observed in 15.5% of the cohort within 6 months of ChEI prescription. Cox regression model with PS as covariate found that patients prescribed rivastigmine (adjusted hazard ratio [aHR] 1.12; 95% CI 1.03-1.33) and galantamine (aHR 1.51; 95% CI 1.24-1.84) were at increased risk of SAEs compared with patients on donepezil. Stratified analyses revealed that rivastigmine was associated with an 18% increased risk for SAEs in females (aHR 1.18; 95% CI 1.06-1.31), and galantamine was associated with a 71% increased risk in males (aHR 1.71; 95% CI 1.17-2.51) compared with donepezil. High and recommended index doses of rivastigmine and galantamine were associated with an increased risk of SAEs compared with donepezil. The findings were consistent in sensitivity analyses. CONCLUSION: The study found that the risk of SAEs varied across individual ChEIs, with sex and dose moderating these effects. Therefore, these moderating effects should be carefully considered in personalizing dementia care.

Risk of overactive bladder associated with cholinesterase inhibitors in dementia.

BACKGROUND: Although cholinesterase inhibitors (ChEIs) are the primary treatment for dementia, they are associated with overactive bladder (OAB), necessitating antimuscarinic use. Limited data exist regarding the risk of OAB across individual ChEIs in dementia. This study evaluated the risk of OAB associated with individual ChEIs in older adults with dementia. METHODS: This was a new user retrospective cohort study using Medicare claims data involving Parts A, B, and D claims dataset from 2013 to 2015. The study included older adults (aged 65 and older) with a diagnosis of dementia using donepezil, galantamine, or rivastigmine. New ChEI claims were identified with a 6-month baseline washout period. Patients with OAB diagnosis or any antimuscarinic or mirabegron use in the baseline period were excluded. The primary outcome of interest was OAB diagnosis or prescription of antimuscarinics or mirabegron within 6 months of ChEI initiation. Multivariable cox proportional hazards regression with propensity scores (PS) as covariates and inverse probability of treatment weighting generated using generalized boosted models was used to assess the risk of OAB among donepezil, galantamine, and rivastigmine users. RESULTS: The study included 524,975 older adults with dementia who were incident users of ChEIs (donepezil 80.72%, rivastigmine 16.41%, galantamine 2.87%). Overall, OAB diagnosis/antimuscarinic/mirabegron prescription was observed in 5.07% of the cohort within 6 months of ChEIs prescription. The Cox regression model with PS as covariate approach found that donepezil use increased the risk of OAB compared to rivastigmine (aHR, 1.13; 95% CI, 1.08-1.28; p < 0.0001). However, there was no differential risk of OAB between galantamine and rivastigmine. The findings were consistent with the generalized boosted models. CONCLUSIONS: The study found that the risk of OAB varies across individual ChEIs with an increased risk of OAB with donepezil compared to rivastigmine. The study findings suggest the need to understand and manage medication-related morbidity in older adults with dementia.

Antimuscarinic Cascade Across Individual Cholinesterase Inhibitors in Older Adults with Dementia.

BACKGROUND: Acetylcholinesterase inhibitors (AChEIs) have been associated with an increased risk of starting antimuscarinic treatment to treat overactive bladder (OAB)-an example of a prescribing cascade. Limited comparative data exist regarding the prescribing cascade of antimuscarinics across individual AChEIs in older adults with dementia. OBJECTIVE: This study examined the association between individual AChEI use and antimuscarinic cascade in older adults with dementia. METHODS: We conducted a new user retrospective cohort study from January 2005 to December 2018 using data from the TriNetX electronic medical record database, a federated electronic medical records network in the US. The cohort included patients 65 years or older with a diagnosis of dementia using AChEIs (donepezil, galantamine, or rivastigmine). Individual AChEIs were identified with index dates from 1 January 2006 to 31 June 2018, with a 1-year washout period. The study excluded patients with any antimuscarinic use and OAB diagnosis 1 year before the AChEI index date. The primary outcome of interest was the prescription of antimuscarinics within 6 months of the AChEI index date. A Cox proportional hazard model was used to assess the association between individual incident AChEI use and antimuscarinic prescribing cascade after controlling for several covariates. RESULTS: The study included 47,059 older adults with dementia who were incident users of AChEIs. Most of these patients were initiated with donepezil (83.1%), followed by rivastigmine (12.3%) and galantamine (4.6%). Overall, 8.16% of the study cohort had incident OAB diagnosis or antimuscarinic prescription. Antimuscarinics were initiated by 1725 (3.7%) older adults with dementia within 6 months of AChEI prescription, and cascade varied widely across individual agents-donepezil (3.9%), rivastigmine (2.6%), and galantamine (2.9%). Cox proportional hazard analyses revealed that donepezil users had an increased risk of receiving antimuscarinics (adjusted hazard ratio 1.55, 95% confidence interval 1.31-1.83) compared with rivastigmine. The findings were consistent in sensitivity analyses. CONCLUSION: This study found that donepezil use is more likely to lead to antimuscarinic cascade than rivastigmine. Future studies are needed to determine the potential consequences of this cascade in dementia.

A naturalistic observation study of medication counseling practices at retail chain pharmacies.

OBJECTIVE: This study evaluated medication counseling procedures and trends at retail pharmacies in the Houston metropolitan area through a naturalistic observational study. METHODS: A blinded cross-sectional observational study was conducted at retail pharmacies in the Houston metropolitan area. Data were collected by trained observers utilizing an observational log, to record various parameters that could have an impact on the duration of patient-pharmacist interaction in a naturalistic pharmacy practice setting. Additionally, indicators of counseling such as utilization of the counseling window and performance of show-and-tell were recorded. Statistical analyses included descriptive statistics, t-tests, Pearson correlations, ANOVAs, and multiple linear regressions. RESULTS: One hundred and sixty-five interactions between patients and pharmacy staff were recorded at 45 retail pharmacies from 7 retail pharmacy chains. The counseling window was utilized in only 3 (1.81%) out of 165 observations and the show-and-tell process was observed in just 1(0.61%) interaction during this study. Mean (SD) interaction time between patient and pharmacists [159.50 (84.50)] was not statistically different (p>0.05) from the mean interaction time between patients and pharmacy technicians [139.30 (74.19)], irrespective of type of the retail chain observed. However, it was influenced by the number of patients waiting in queue. Patient wait time significantly differed by the time of the day the interaction was observed, weekends and weekdays had significantly different wait times and patient interaction times Multiple linear regression analyses indicated that, patient interaction time, pharmacy chain type, initial contact (pharmacist/technician), and time of the day, were significantly associated with patient wait time whereas patient wait time, pharmacy chain type, number of patients in queue, and number of pharmacy technician were significantly associated with interaction time. CONCLUSIONS: Our study found that the key indicators of counseling including the use of the counseling window and the show-and-tell process were absent, suggesting lack of adequate pharmacists counseling. Further studies are needed to evaluate the validity of this conclusion and the role of pharmacy services and its value towards medication use and safety.

A naturalistic observation study of medication counseling practices at retail chain pharmacies

OBJECTIVE: This study evaluated medication counseling procedures and trends at retail pharmacies in the Houston metropolitan area through a naturalistic observational study. METHODS: A blinded cross-sectional observational study was conducted at retail pharmacies in the Houston metropolitan area. Data were collected by trained observers utilizing an observational log, to record various parameters that could have an impact on the duration of patient-pharmacist interaction in a naturalistic pharmacy practice setting. Additionally, indicators of counseling such as utilization of the counseling window and performance of show-and-tell were recorded. Statistical analyses included descriptive statistics, t-tests, Pearson correlations, ANOVAs, and multiple linear regressions. RESULTS: One hundred and sixty-five interactions between patients and pharmacy staff were recorded at 45 retail pharmacies from 7 retail pharmacy chains. The counseling window was utilized in only 3 (1.81%) out of 165 observations and the show-and-tell process was observed in just 1(0.61%) interaction during this study. Mean (SD) interaction time between patient and pharmacists [159.50 (84.50)] was not statistically different (p > 0.05) from the mean interaction time between patients and pharmacy technicians [139.30 (74.19)], irrespective of type of the retail chain observed. However, it was influenced by the number of patients waiting in queue. Patient wait time significantly differed by the time of the day the interaction was observed, weekends and weekdays had significantly different wait times and patient interaction times Multiple linear regression analyses indicated that, patient interaction time, pharmacy chain type, initial contact (pharmacist/technician), and time of the day, were significantly associated with patient wait time whereas patient wait time, pharmacy chain type, number of patients in queue, and number of pharmacy technician were significantly associated with interaction time. CONCLUSIONS: Our study found that the key indicators of counseling including the use of the counseling window and the show-and-tell process were absent, suggesting lack of adequate pharmacists counseling. Further studies are needed to evaluate the validity of this conclusion and the role of pharmacy services and its value towards medication use and safety

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