Publications

BACKGROUND & AIMS: It is not clear what factors affect risk of chronic kidney disease (CKD) in patients with inflammatory bowel disease (IBD); increased risk has been inconsistently associated with use of 5-aminosalicylates (5-ASAs). We aimed to calculate the relative hazard of CKD among patients with IBD, adjusted for CKD risk factors, and to determine whether IBD medications are associated with change in estimated glomerular filtration rate (eGFR).

METHODS: We performed a retrospective cohort study of data from The Health Improvement Network. Patients with IBD (n = 17,807) were matched for age, sex, and practice to individuals without IBD (n = 63,466). The relative hazard of CKD, stages 3 through 5D, in patients with IBD was calculated using a Cox proportional hazards model adjusted for common CKD risk factors. We also evaluated the association of 5-ASAs, azathioprine, and methotrexate with change in eGFR using a longitudinal model.

RESULTS: After we controlled for risk factors associated with CKD, we found IBD to be associated with development of CKD in patients 16-77 years old. As patient age increased, the adjusted hazard ratio for CKD decreased monotonically, from 7.88 (95% CI, 2.56-24.19) at age 16 to 1.13 (95% CI, 1.01-1.25) at age 77. In the longitudinal analysis, exposure to 5-ASAs or methotrexate was not associated with change in eGFR, whereas azathioprine was associated with a slightly higher eGFR (0.32 mL/min/1.73 m2; 95% CI, 0.16-0.48).

CONCLUSIONS: In a retrospective study of more than 80,000 persons, we found that IBD is associated with increased risk of CKD, and the hazard ratio is highest among younger patients. Commonly used non-biologic therapeutic agents were not associated with lower eGFR.

BACKGROUND AND AIMS: There are limited data on the most cost-effective sequencing of biologics for ulcerative colitis [UC].

METHODS: We used Markov modelling to identify the most cost-effective position for vedolizumab among biologics for steroid-dependent UC, with a base-case of a 35-year-old male. We assessed three treatment algorithms, with vedolizumab use: prior to an initial anti-tumour necrosis factor alpha [anti-TNFα] and azathioprine [Algorithm 1]; prior to a second anti-TNF and azathioprine [Algorithm 2]; and prior to colectomy [Algorithm 3]. The initial anti-TNF could be either infliximab or adalimumab. Transition probabilities, costs, and quality-adjusted life-year estimates were derived from published estimates, Medicare, and the Nationwide Inpatient Sample. Primary analyses included 100 trials of 100 000 individuals over 1 year, with a willingness-to-pay threshold of US$100,000. Multiple sensitivity analyses were conducted to assess our findings.

RESULTS: From a population perspective, when both infliximab and adalimumab are available, vedolizumab was preferred as the first biologic if ≥14% of initial anti-TNF use was adalimumab. If infliximab is the primary biologic, vedolizumab use after infliximab [Algorithm 2] and prior to adalimumab was the most cost-effective strategy. All models were sensitive to biologic pricing.

CONCLUSIONS: This simulation demonstrated that the most cost-effective strategy in UC depends on the proportion of patients using adalimumab as the initial anti-TNF. If adalimumab was ≥14%, vedolizumab was preferred as the first biologic. When only infliximab was available for first-line therapy, the most cost-effective position of vedolizumab was prior to cycling to adalimumab.

IMPORTANCE: Most studies that have examined drug prices have focused on list prices, without accounting for manufacturer rebates and other discounts, which have substantially increased in the last decade.

OBJECTIVE: To describe changes in list prices, net prices, and discounts for branded pharmaceutical products for which US sales are reported by publicly traded companies, and to determine the extent to which list price increases were offset by increases in discounts.

DESIGN, SETTING, AND PARTICIPANTS: Retrospective descriptive study using 2007-2018 pricing data from the investment firm SSR Health for branded products available before January 2007 with US sales reported by publicly traded companies (n = 602 drugs). Net prices were estimated by compiling company-reported sales for each product and number of units sold in the US.

EXPOSURES: Calendar year.

MAIN OUTCOMES AND MEASURES: Outcomes included list and net prices and discounts in Medicaid and other payers. List prices represent manufacturers' price to wholesalers or direct purchasers but do not account for discounts. Net prices represent revenue per unit of the product after all manufacturer concessions are accounted for (including rebates, coupon cards, and any other discount). Means of outcomes were calculated each year for the overall sample and 6 therapeutic classes, weighting each product by utilization and adjusting for inflation.

RESULTS: From 2007 to 2018, list prices increased by 159% (95% CI, 137%-181%), or 9.1% per year, while net prices increased by 60% (95% CI, 36%-84%), or 4.5% per year, with stable net prices between 2015 and 2018. Discounts increased from 40% to 76% in Medicaid and from 23% to 51% for other payers. Increases in discounts offset 62% of list price increases. There was large variability across classes. Multiple sclerosis treatments (n = 4) had the greatest increases in list (439%) and net (157%) prices. List prices of lipid-lowering agents (n = 11) increased by 278% and net prices by 95%. List prices of tumor necrosis factor inhibitors (n = 3) increased by 166% and net prices by 73%. List prices of insulins (n = 7) increased by 262%, and net prices by 51%. List prices of noninsulin antidiabetic agents (n = 10) increased by 165%, and net prices decreased by 1%. List price increases were lowest (59%) for antineoplastic agents (n = 44), but discounts only offset 41% of list price increases, leading to 35% increase in net prices.

CONCLUSIONS AND RELEVANCE: In this analysis of branded drugs in the US from 2007 to 2018, mean increases in list and net prices were substantial, although discounts offset an estimated 62% of list price increases with substantial variation across classes.

Value-based pharmaceutical contracts (VBPCs) are performance-based reimbursement agreements between healthcare payers and pharmaceutical manufacturers in which the price, amount, or nature of reimbursement is tied to value-based outcomes. VBPCs are often complex, and the nature of who benefits and in what ways can be unclear. We discuss how VBPCs compare with value-based payer-provider arrangements in terms of performance-based reimbursements and alignment of incentives. In addition, we examine how VBPCs can affect costs, clinical outcomes, and access to medications. Because these contracts are unlikely to reduce costs in isolation, we recommend taking a patient-centered approach when developing VBPCs and tying VBPCs to more overarching payer drug cost reduction strategies.

Value-based pharmaceutical contracts (VBPCs) are performance-based reimbursement agreements between health care payers and pharmaceutical manufacturers in which the price, quantity, or nature of reimbursement is tied to value-based outcomes. As value-based payment models have permeated through much of the health care payment landscape via reimbursement to payers and providers, VBPCs offer opportunities for manufacturers to similarly engage in performance-based models. This article compares 2 VBPC schemes: "pay-for-failure" schemes, in which manufacturers offer rebates or discounts to payers for treatment failure, and "pay-for-success" schemes, in which manufacturers offer rebates or discounts to payers for treatment success. Each method has its own short-term and long-term trade-offs, and both lead to some degree of misaligned incentives between payers and manufacturers. These incentive differences have important downstream effects, influencing patient selection, provision of wraparound services, and nature of reimbursements. This analysis contrasts potential benefits and disadvantages for each of these approaches and offers potential solutions to address misalignment. For example, although pay-for-success models may be more aligned between payers and manufacturers, pay-for-failure contracts can be innovative and effective in controlling costs and/or improving outcomes. To illustrate, VBPCs aimed to reduce costs could incorporate total cost of care reduction as a value-based outcome. The authors encourage payers and manufacturers to consider a blended alternative where pay-for-failure and pay-for-success outcomes could be incorporated as VBPC outcomes. Since little is known about the effect of each scheme on outcomes, further research on VBPCs is necessary to fully understand how differing incentives ultimately affect clinical outcomes and costs. DISCLOSURES: No outside funding supported the writing of this article. Good and Kelly are employed by the UPMC Centers for Value-Based Pharmacy Initiatives and High-Value Health Care, and Parekh was employed by the UPMC Centers for Value-Based Pharmacy Initiatives and High-Value Health Care at the time of this study. The authors have no other disclosures to report.

BACKGROUND: Direct-to-consumer advertising (DTCA) of prescription drugs impacts patients' requests for medications, and clinician prescribing. However, the impact of DTCA during the Super Bowl has not been previously described.

OBJECTIVE: Evaluate the impact of prescription drug DTCA during the Super Bowl on drug utilization using 2014-2016 Medicare data.

METHODS: Efinaconazole was advertised during Super Bowls XLIX (02/01/2015) and L (02/07/2016). The number of prescriptions for efinaconazole and for a comparator drug, tavaborole, were calculated in 31-day intervals from July 2014-December 2016. Interrupted time-series analysis models were created to test changes in trends of prescriptions for efinaconazole and tavaborole.

RESULTS: Following Super Bowl XLIX, the number of prescriptions per 100,000 Medicare beneficiaries increased by 91% for efinaconazole, and 275% for tavaborole. After Super Bowl L, the number of prescriptions increased significantly for efinaconazole (p-value<0.001), but not for tavaborole (p = 0.70). Interrupted time-series analyses estimated that, in the absence of DTCA during Super Bowl XLIX, prescriptions for efinaconazole would have increased by 40%, instead of the observed 91%. For tavaborole, prescriptions would have increased by 90% instead of 275%.

CONCLUSIONS: DTCA during the Super Bowl resulted in sharp increases in utilization of the prescription drug advertised, which supports further regulation of DTCA.

BACKGROUND AND AIMS: Despite the significant medical and economic consequences of coexisting alcohol use disorder (AUD) in patients with cirrhosis, little is known about AUD treatment patterns and their impact on clinical outcomes in this population. We aimed to characterize the use of and outcomes associated with AUD treatment in patients with cirrhosis.

APPROACH AND RESULTS: This retrospective cohort study included Veterans with cirrhosis who received Veterans Health Administration care and had an index diagnosis of AUD between 2011 and 2015. We assessed the baseline factors associated with AUD treatment (pharmacotherapy or behavioral therapy) and clinical outcomes for 180 days following the first AUD diagnosis code within the study time frame. Among 93,612 Veterans with cirrhosis, we identified 35,682 with AUD, after excluding 2,671 who had prior diagnoses of AUD and recent treatment. Over 180 days following the index diagnosis of AUD, 5,088 (14%) received AUD treatment, including 4,461 (12%) who received behavioral therapy alone, 159 (0.4%) who received pharmacotherapy alone, and 468 (1%) who received both behavioral therapy and pharmacotherapy. In adjusted analyses, behavioral and/or pharmacotherapy-based AUD treatment was associated with a significant reduction in incident hepatic decompensation (6.5% vs. 11.6%, adjusted odds ratio [AOR], 0.63; 95% confidence interval [CI], 0.52, 0.76), a nonsignificant decrease in short-term all-cause mortality (2.6% vs. 3.9%, AOR, 0.79; 95% CI, 0.57, 1.08), and a significant decrease in long-term all-cause mortality (51% vs. 58%, AOR, 0.87; 95% CI, 0.80, 0.96).

CONCLUSIONS: Most Veterans with cirrhosis and coexisting AUD did not receive behavioral therapy or pharmacotherapy treatment for AUD over a 6-month follow-up. The reductions in hepatic decompensation and mortality suggest that future studies should focus on delivering evidence-based AUD treatments to patients with coexisting AUD and cirrhosis.

BACKGROUND: After non-fatal opioid overdoses, opioid prescribing patterns are often unchanged and the use of medications for opioid use disorder (MOUDs) remains low. Whether such prescribing differs by race/ethnicity remains unknown.

OBJECTIVE: To assess the association of race/ethnicity with the prescribing of opioids and MOUDs after a non-fatal opioid overdose.

DESIGN: Retrospective cohort study.

PARTICIPANTS: Patients prescribed ≥ 1 opioid from July 1, 2010, to September 30, 2015, with a non-fatal opioid overdose in the Veterans Health Administration (VA).

MAIN MEASURES: Primary outcomes were the proportion of patients prescribed: (1) any opioid during the 30 days before and after overdose and (2) MOUDs within 30 days after overdose by race and ethnicity. We conducted difference-in-difference analyses using multivariable regression to assess whether the change in opioid prescribing from before to after overdose differed by race/ethnicity. We also used multivariable regression to test whether MOUD prescribing after overdose differed by race/ethnicity.

KEY RESULTS: Among 16,210 patients with a non-fatal opioid overdose (81.2% were white, 14.3% black, and 4.5% Hispanic), 10,745 (66.3%) patients received an opioid prescription (67.1% white, 61.7% black, and 65.9% Hispanic; p < 0.01) before overdose. After overdose, the frequency of receiving opioids was reduced by 18.3, 16.4, and 20.6 percentage points in whites, blacks, and Hispanics, respectively, with no significant difference-in-difference in opioid prescribing by race/ethnicity (p = 0.23). After overdose, 526 (3.2%) patients received MOUDs (2.9% white, 4.6% black, and 5.5% Hispanic; p < 0.01). Blacks (adjusted OR (aOR) 1.6; 95% CI 1.2, 1.9) and Hispanics (aOR 1.8; 95% CI 1.2, 2.6) had significantly larger odds of receiving MOUDs than white patients.

CONCLUSIONS: In a national cohort of patients with non-fatal opioid overdose in VA, there were no racial/ethnic differences in changes in opioid prescribing after overdose. Although blacks and Hispanics were more likely than white patients to receive MOUDs in the 30 days after overdose, less than 4% of all groups received such therapy.