Individual and social determinants of adherence to sodium-glucose cotransporter 2 inhibitor therapy: A trajectory analysis.

BACKGROUND: Sodium-glucose cotransporter 2 inhibitors (SGLT2is) are known to improve cardiovascular and renal outcomes in patients with type 2 diabetes (T2D). Understanding the longitudinal patterns of adherence and the associated predictors is critical to addressing the suboptimal use of this outcome-improving treatment. OBJECTIVE: To characterize the distinct trajectories of adherence to SGLT2is in patients with T2D and to identify patient characteristics and social determinants of health (SDOHs) associated with SGLT2i adherence. METHODS: In this retrospective cohort study, we identified patients with T2D who initiated and filled at least 1 SGLT2i prescription according to 2012-2016 national Medicare claims data. The monthly proportion of days covered with SGLT2is for each patient was incorporated into group-based trajectory models to identify groups with similar adherence patterns. A multinomial logistic regression model was constructed to examine the association between patient characteristics and group membership. In addition, the association between context-specific SDOHs (eg, neighborhood median income and neighborhood employment rate) and adherence to an SGLT2i regimen was explored in both the overall cohort and the racial and ethnic subgroups. RESULTS: The final sample comprised 6,719 patients with T2D. Four trajectories of SGLT2i adherence were identified: continuously adherent users (49.6%), early discontinuers (27.5%), late discontinuers (14.5%), and intermediately adherent users (8.4%). Patient age, sex, race, diabetes duration, and Medicaid eligibility were significantly associated with trajectory group membership. Areas with a higher unemployment rate, lower income level, lower high school education rate, worse nutrition environment, fewer health care facilities, and greater Area Deprivation Index scores were found to be associated with low adherence to SGLT2is. CONCLUSIONS: Four distinct trajectories of adherence to SGLT2is were identified, with only half of the patients remaining continuously adherent to their treatment regimen during the first year after initiation. Several contextual SDOHs were associated with suboptimal adherence to SGLT2is.

Comparison of oral anticoagulation use and adherence among Medicare beneficiaries enrolled in stand-alone prescription drug plans vs Medicare Advantage prescription drug plans.

BACKGROUND: For atrial fibrillation (AF) patients, oral anticoagulants (OACs) can reduce the risk of stroke by 60%; however, nearly 50% of patients recommended to receive OACs do not receive therapy. Integrated insurers that cover pharmacy and medical benefits may be incentivized to improve OAC use and adherence because they benefit from offsets in medical costs associated with prevented strokes. OBJECTIVE: To compare OAC use and adherence between AF patients enrolled in Medicare stand-alone prescription drug plans (PDPs), which only cover pharmacy benefits, and those enrolled in Medicare Advantage prescription drug (MAPD) plans, which cover medical and pharmacy benefits. METHODS: This was a retrospective cohort study, conducted using 2014-2016 Medicare claims data from the Centers for Medicare & Medicaid Services and a large regional health plan in Pennsylvania. Primary outcomes included OAC use and OAC adherence. OAC use was measured as filling at least 1 prescription for an OAC after AF diagnosis. OAC adherence was defined as having greater than or equal to 80% of days covered with an OAC. We constructed conditional logistic regression models in propensity score-matched samples to test the association between enrollment in PDPs or MAPD plans and outcomes. RESULTS: There were 2,551 AF patients enrolled in PDPs and 4,502 in MAPD plans before propensity score matching. The propensity score-matched sample included 2,537 patients in each group. OAC use was higher among MAPD beneficiaries (74%-76%) compared with PDP beneficiaries (70%; P < 0.001), and 41%-42% of MAPD beneficiaries were adherent to OACs, compared with 34% of PDP beneficiaries (P < 0.001). In adjusted analyses among propensity score-matched samples, PDP enrollment was associated with lower odds of OAC use (OR = 0.67, 95% CI = 0.56-0.81) and adherence (OR = 0.68, 95% CI = 0.59-0.78) compared with MAPD enrollment. CONCLUSIONS: AF patients enrolled in MAPD plans were more likely to use and adhere to OACs compared with PDP enrollees. These results may reflect the financial incentives of MAPD plans to improve guideline-recommended OAC use, since MAPD insurers bear the risk of pharmacy and medical costs and thus may benefit from cost savings associated with averted stroke events. As efforts to improve use and adherence of OACs in AF patients increase, focus should be given to how insurance benefit designs can affect medication use. DISCLOSURES: No outside funding supported this study. Hernandez has received personal fees from BMS and Pfizer, unrelated to this study. The other authors have nothing to disclose.

Primary care provider payment models and adherence to anticoagulation in patients with atrial fibrillation.

BACKGROUND: Oral anticoagulation (OAC) is recommended for the prevention of stroke in atrial fibrillation (AF). However, only 50%-60% of AF patients in the United States are treated with OAC, and 60% of them adhere to OAC therapy over time. OBJECTIVES: To (1) compare adherent use of OAC between AF patients who received primary care from practices involved in shared-savings models and patients who received care from practices not involved in shared savings and (2) examine the trend of adherence to OAC over time. Because OAC can save downstream medical costs associated with averted stroke events, we hypothesized that OAC adherence would be higher among patients receiving care from practices involved in shared savings. METHODS: Using 2014-2019 claims data from a health insurer in western Pennsylvania, we identified 20,637 AF patients from 2015-2018. Patients were followed from the first AF diagnosis (index date) for 12 months or until disenrollment. We categorized patients according to the payment model of the practice from which they received primary care: shared savings (n = 8,844) and no shared savings (n = 11,793). The primary outcome was adherent use of OAC therapy, which was defined as having at least 80% of the followup period covered with OAC. Secondary outcomes included adherent use of direct oral anticoagulants (DOACs) and adherent use of warfarin. We constructed logistic regression models to assess the association between involvement in shared savings and adherent use of OAC, while controlling for demographics, clinical characteristics, and index year. RESULTS: 34% of patients in the shared-savings group adhered to OAC, compared with 32.7% in the no shared-savings group (P = 0.04). After adjustment, adherence was higher for the shared-savings group for OAC (adjusted odds ratio [aOR] = 1.07, 95% CI = 1.01-1.14) and warfarin (aOR = 1.11, 95% CI = 1.02-1.20) compared with the no shared-savings group. However, the odds of adherent use of DOACs did not statistically differ between shared savings and no shared savings (aOR = 0.99, 95% CI = 0.91-1.08). The odds of adherent OAC use increased over time: the aOR of adherent use of OAC was 1.21 (95% CI = 1.09-1.34) for index year 2016; 1.50 (95% CI = 1.36-1.67) for 2017; and 1.78 (95% CI 1.60-1.98) for 2018, all compared with 2015. CONCLUSIONS: Receipt of primary care from a practice involved in shared savings was associated with a higher adherent use of OAC and warfarin for patients with atrial fibrillation. Furthermore, adherent use of OAC improved over time for both treatment groups. Our research demonstrates that the alignment of financial incentives between providers and insurers may improve the use of therapies with downstream cost-saving potential. DISCLOSURES: This project was funded by the National Heart, Lung and Blood Institute (grant number K01HL142847). Hernandez has received consulting fees from Pfizer and BMS, outside of the submitted work. The other authors have nothing to disclose.

Emerging treatments for lupus nephritis: health equity considerations in clinical research and coverage.

DISCLOSURES: No funding was received for the writing of this commentary. The authors report no conflicts of interest.

A decade of increases in Medicare Part B pharmaceutical spending: what are the drivers?

BACKGROUND: Medicare Part B pharmaceutical spending has increased rapidly, more than doubling in 2006-2017. Yet, it is unclear whether this increase was driven by increased utilization or increased cost per claim. OBJECTIVE: To evaluate the relative impact of changes in drug utilization and cost per claim on changes in Medicare Part B pharmaceutical spending in 2008-2016 overall, by drug type (specialty and nonspecialty) and therapeutic category. METHODS: In this retrospective descriptive study, we extracted all claims in 2008-2016 for separately payable Part B drugs from a 5% random sample of Medicare beneficiaries. Our study included 3 outcomes calculated annually for all included drugs: (1) spending, defined as the sum of total payments; (2) utilization, defined as total number of claims; and (3) cost per claim, defined as spending divided by the number of claims. Estimates of spending and utilization were expressed per beneficiary-year. Spending and cost per claim were adjusted for inflation. For each outcome, we calculated relative changes in 2008-2016. We repeated analyses stratifying by drug type (specialty and nonspecialty) and therapeutic class. RESULTS: Pharmaceutical spending in Medicare Part B increased by 34% from 2008-2016, driven by a 53% increase in the cost per claim. Utilization decreased by 12%. Spending on specialty drugs increased by 56%, driven by a 48% increase in the cost per claim and a 6% utilization increase. Spending on nonspecialty drugs decreased by 32% driven by an 18% reduction in the cost per claim and a 17% reduction in utilization. Spending on ophthalmic preparations increased by 281%, driven by a 238% utilization increase and a 13% increase in the cost per claim. Spending on antiarthritic and immunologic agents increased by 159%, driven by a 117% increase in the cost per claim and a 19% utilization increase. CONCLUSIONS: Medicare Part B pharmaceutical spending grew in recent years, despite decreased utilization, driven by an overall increase in the cost per claim. This was a product of rising drug prices and increased utilization of more expensive specialty drugs. These findings support the development of policies that aim to spur competition and control price growth of provider-administered drugs. DISCLOSURES: The authors acknowledge funding from the Myers Family Foundation. Hernandez was funded by the National Heart, Lung and Blood Institute (grant number K01HL142847). Shrank is an employee of Humana. Good is an employee of the UPMC Health Plan Insurance Services Division. There are no other potential conflicts of interest to disclose.

Association between opioid dose escalation and time to death in a comfort measures only population.

PURPOSE: Opioids are crucial to the relief of pain and dyspnea experienced by patients dying in the hospital setting; however, there are concerns about the association of opioid dosage with hastened death via opioid-induced respiratory depression, and there is little published evidence regarding the association between opioid dose escalation and time to death in the inpatient comfort measures only (CMO) population. METHODS: The medical records of adult patients admitted to 2 hospitals who had an active CMO order at the time of death and received opioid dose escalations after CMO pronouncement were assessed in a retrospective cohort study. Patients were categorized into higher and lower opioid dose escalation groups according to an institutional palliative care symptom guide. A Cox proportional hazards model was constructed to test the associations between dose escalation group, patient sex, opioid naivety, palliative care consultation, and opioid dosage after CMO pronouncement (independent variables) and time to death (dependent variable). RESULTS: In the 71-patient cohort, 39 patients (54.9%) were male and 32 (45.1%) were female. The mean (SD) age of patients was 67.2 (16.6) years. Higher dose escalation (n = 46, 64.8%) was associated with a nonsignificant decrease in survival time compared to lower dose escalation (n = 25, 35.2%), with a mean difference in time to death of 19.8 hours (hazard ratio [HR], 1.67; 95% confidence interval [CI], 0.94-2.97). Receipt of a palliative care consult (n = 56, 78.9%) during the final hospital visit was associated with increased survival time (mean difference, 20.1 hours; HR, 0.32; 95% CI, 0.16-0.63). CONCLUSION: Time to death in an inpatient CMO population was not significantly associated with the degree of opioid dose escalation.

Trends in list prices, net prices, and discounts of self-administered injectable tumor necrosis factor inhibitors.

BACKGROUND: List prices of tumor necrosis factor (TNF) inhibitors drastically increased during the last decade, but previous research has shown that half of these increases were offset by rising manufacturer discounts. It remains unclear to what extent manufacturers' discounts have offset increases in list prices of each self-administered injectable TNF inhibitor. Evaluating trends in net prices and discounts at the product level will be paramount in understanding the role of competition in the biologic market. OBJECTIVES: To (a) describe product-level changes in net prices of each self-administered injectable TNF inhibitor available in 2007-2019 and (b) quantify to what extent manufacturer discounts have offset increases in list prices. METHODS: We obtained 2007-2019 pricing data for etanercept, adalimumab, certolizumab, and golimumab from the investment firm SSR Health, which uses company-reported sales to estimate net prices and discounts for brand products manufactured by publicly traded companies. For each drug and year, we calculated annual costs of treatment for patients with rheumatoid arthritis based on list and net prices and discounts in Medicaid and other payers. RESULTS: From 2007-2019, list prices of etanercept and adalimumab increased by 293% and 295%, respectively; however, discounts offset 47% and 45% of these increases, leading to net price increases of 171% and 203%. List prices of golimumab and certolizumab increased by 183% and 182%, respectively, but with discounts offsetting 58% and 59% of these increases, net prices increased by 103% and 109%. Net prices of golimumab started to decrease after 2016, while net prices of adalimumab and certolizumab experienced their first drop in 2019. Across the study period, discounts in Medicaid and in other payers increased, respectively, from 21% to 85% and 6% to 32% for etanercept; from 26% to 88% and 19% to 35% for adalimumab; from 28% to 63% and 22% to 46% for golimumab; and from 29% to 83% and 27% to 47% for certolizumab. CONCLUSIONS: Despite growing manufacturer discounts, net prices of self-administered injectable TNF inhibitors still increased at a mean annual rate of 9.6% in 2007-2019. This led to net prices tripling for adalimumab and more than doubling for etanercept, golimumab, and certolizumab. DISCLOSURES: This study was funded by the Myers Family Foundation. Hernandez is funded by the National Heart, Lung and Blood Institute (grant number K01HL142847). Funding sources had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. Hernandez has served on Pfizer's scientific advisory board. The other authors have nothing to disclose.

Outcomes of Patients With Atrial Fibrillation Newly Recommended for Oral Anticoagulation Under the 2014 American Heart Association/American College of Cardiology/Heart Rhythm Society Guideline.

BACKGROUND: In March 2014, the American Heart Association updated their guidelines for the management of oral anticoagulation (OAC) in atrial fibrillation, recommending OAC for all patients with CHA2DS2-VASc ≥2. Previously, only patients with CHADS2 ≥2 were recommended for anticoagulation. This study compared effectiveness and safety outcomes of OAC among patients who would receive OAC using the 2014 guidelines but not the 2011 guidelines. METHODS AND RESULTS: Using claims data from a 5% sample of 2013-2014 Medicare beneficiaries, we identified patients with initially diagnosed atrial fibrillation between 2013 and 2014 and selected those who would receive OAC under the 2014 guidelines but not the 2011 guidelines (those with CHA2DS2-VASc score ≥2 or CHADS2 score <2). Patients were categorized according to their use of OAC after first atrial fibrillation diagnosis (2937 users and 2914 nonusers). Primary outcomes included the composite of ischemic stroke, systemic embolism and death, and any bleeding event. Cox proportional hazard models were constructed to compare the risk of primary outcomes between the 2 groups, while controlling for patient demographic and clinical characteristics. There was no difference in the combined risk of stroke, systemic embolism, and death between the treatment groups (hazard ratio, 1.00; 95% confidence interval, 0.84-1.20). The risk of bleeding was higher for patients receiving OAC than for patients not receiving OAC (hazard ratio, 1.70, 95% confidence interval, 1.46-1.97). CONCLUSIONS: The benefit of OAC is not well defined in this patient population, and new studies that minimize residual confounding are needed to fully understand the risk/benefit of OAC in patients with atrial fibrillation and low to moderate stroke risk.

Using predictive analytics and big data to optimize pharmaceutical outcomes.

PURPOSE: The steps involved, the resources needed, and the challenges associated with applying predictive analytics in healthcare are described, with a review of successful applications of predictive analytics in implementing population health management interventions that target medication-related patient outcomes. SUMMARY: In healthcare, the term big data typically refers to large quantities of electronic health record, administrative claims, and clinical trial data as well as data collected from smartphone applications, wearable devices, social media, and personal genomics services; predictive analytics refers to innovative methods of analysis developed to overcome challenges associated with big data, including a variety of statistical techniques ranging from predictive modeling to machine learning to data mining. Predictive analytics using big data have been applied successfully in several areas of medication management, such as in the identification of complex patients or those at highest risk for medication noncompliance or adverse effects. Because predictive analytics can be used in predicting different outcomes, they can provide pharmacists with a better understanding of the risks for specific medication-related problems that each patient faces. This information will enable pharmacists to deliver interventions tailored to patients' needs. In order to take full advantage of these benefits, however, clinicians will have to understand the basics of big data and predictive analytics. CONCLUSION: Predictive analytics that leverage big data will become an indispensable tool for clinicians in mapping interventions and improving patient outcomes.