Treatment of metastatic melanoma with pazopanib: A report of five patient cases.

Metastatic melanoma has a median length of survival after diagnosis of 6-9 months. Unfortunately, the National Comprehensive Cancer Network clinical practice guidelines for treating stage IV, unresectable, metastatic melanoma are limited with regard to treatment options. Pazopanib (Votrient™) is FDA-approved for advanced soft tissue sarcoma and advanced renal cell carcinoma. Limited research exists for using pazopanib in the treatment of metastatic melanoma. We present five cases in which pazopanib was used in combination with paclitaxel ± carboplatin for treatment of unresectable, metastatic melanoma.

Net Clinical Benefits of Guidelines and Decision Tool Recommendations for Oral Anticoagulant Use among Patients with Atrial Fibrillation.

BACKGROUND: The 2012 American College of Chest Physicians' Evidence-Based Clinical Practice (CHEST), the 2012 European Society of Cardiology, and the 2014 American Heart Association guidelines and published decision tools by LaHaye and Casciano offer oral anticoagulant (OAC) recommendations for patients with atrial fibrillation (AF). The aim of our study was to compare the net clinical benefit (NCB) of OAC prescribing that was concordant with these decision aids. METHODS: A cohort study of the 2001-2013 LifeLink claims data was used. NCB in concordance with each decision aid was defined as adverse events (thromboembolic and major bleed events) prevented per 10,000 person-years. Cox proportional hazard models were used to assess the relative risk of AF adverse events associated in concordance with each decision aid adjusted for potential confounders. FINDINGS: The study included 15,129 patients with AF, contributing 33,512 person-years. The NCB of the CHEST guidelines was the highest (NCB = 30.07; 95% confidence interval [CI] = 28.66, 31.49) and the European Society of Cardiology guidelines the lowest (NCB = 7.38; 95% CI = 5.97, 8.80). Significant unadjusted decreases in the risk of AF adverse events associated with concordant OAC use/nonuse were found for the CHEST guidelines (hazard ratio [HR] = .825; 95% CI = .695, .979), Casciano tool (HR = .838; 95% CI = .706, .995), and LaHaye tool (HR = .841; 95% CI = .709, .999); however, none were significant after multivariate adjustment. CONCLUSION: Concordant OAC use with any of the decision aids except for the aggressive LaHaye tool led to a positive NCB. The decision aids based on the CHA2DS2-VASc algorithm did not consistently improve the NCB compared to CHADS2-based aids. Recommending OAC use when CHA2DS2-VASc score = 1 resulted in a lower NCB when all other factors guiding recommendations were held constant.

SEVERE, PROLONGED, DENOSUMAB-INDUCED HYPOCALCEMIA WITH RECOVERY AFTER 111 DAYS OF HIGH-DOSE CALCIUM SUPPLEMENTATION.

OBJECTIVE: Denosumab is a monoclonal antibody commonly used for the prevention of skeletal-related events in patients with bone metastases from solid tumors. Hypocalcemia is a known adverse effect with denosumab, and we present an unusual case where 2 hypocalcemic events occurred after 1 denosumab treatment. METHODS: A 76-year-old man recently diagnosed with prostate cancer with bone metastasis was given 120 mg denosumab subcutaneously due to extensive bone disease. RESULTS: The patient experienced denosumab-induced hypocalcemia induced by a single denosumab dose which was resolved after 14 days of multiple doses of intravenous calcium gluconate and oral calcium and vitamin D replacement. However, the patient returned with acute kidney injury and severe hypocalcemia (corrected calcium of 6.9 mg/dL) without any additional dose of denosumab. The recovery following the second episode of hypocalcemia was much longer than the initial episode in this patient. CONCLUSION: To our knowledge, this is the first reported case of an additional episode of hypocalcemia following a single denosumab dose. This case highlights the importance of close monitoring of renal function and serum electrolytes following the resolution of denosumab-induced hypocalcemia.

Cost and Utilization Outcomes After Exclusion of Dipeptidyl Peptidase-4 Inhibitors and Other Diabetes Drug Category Changes in a Self-Funded, State Employee Managed Care Plan.

BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors have repeatedly shown no reduction in the clinical outcomes of cardiovascular death, myocardial infarction, stroke, or all-cause mortality. Because the treatment of diabetes is generally one of the top drug categories by cost to health plans and self-funded employers, it is necessary to evaluate coverage of DPP-4 inhibitors, considering their lack of cardiovascular benefit relative to other treatment options. OBJECTIVE: To describe the cost and utilization outcomes of drugs used to treat diabetes after exclusion of DPP-4 inhibitors in a self-funded managed care plan. METHODS: This study was a retrospective, descriptive analysis of the cost and utilization outcomes after exclusion of DPP-4 inhibitors. Pharmacy claims data and plan membership were analyzed 6 months before DPP-4 inhibitor exclusion (preperiod: December 1, 2016-May 31, 2017) and 6 months after DPP-4 inhibitor coverage ended for all users (postperiod: September 1, 2017-February 28, 2018). The allowed amount, which is not influenced by overlapping plan copay changes, and utilization per member per month (PMPM) were used to estimate the effect of the DPP-4 inhibitor benefit exclusion on plan costs for the antidiabetic class. RESULTS: From preperiod to postperiod, all DPP-4 inhibitor products decreased in utilization by 3.02 claims per 1,000 members per month (PTMPM). Glucagon-like peptide-1 receptor agonists, insulins, sodium-glucose cotransporter-2 inhibitors, and thiazolidinedione claims increased by 0.72, 0.43, 0.30, and 0.48 claims PTMPM, respectively, but there was an absolute decrease of 1.35 claims for antidiabetic medications per 1,000 plan members. However, the days supplied PMPM increased from 2.55 to 2.61 (2.3%) days. Allowed amount PMPM increased by $0.27 from $12.19 in the preperiod to $12.31 in the postperiod (2.2%). However, it is estimated that drug cost inflation accounted for over half of the PMPM increase in allowed costs. CONCLUSIONS: The observed increase in the allowed amount PMPM was attributable in similar amounts by an increase in utilization of medications with higher cost per day supplied and higher drug prices. Future research will evaluate patient-level effects of this benefit change in terms of antidiabetic medication utilization and outcomes. DISCLOSURES: No outside funding supported this study. Davis, Bemberg, and Johnson currently work for or previously worked for the UAMS Evidence-Based Prescription Drug Program, which advises the Employee Benefits Division (EBD) on pharmacy benefit management. The EBD did not provide any additional funding for this study. McAdam-Marx reports grants from AstraZeneca and Sanofi Aventis outside the submitted work. The other authors have no other relevant information to disclose.

A 30-month evaluation of the effects on the cost and utilization of proton pump inhibitors from adding omeprazole OTC to drug benefit coverage in a state employee health plan.

OBJECTIVE: On March 1, 2004, the state employee health plan began covering omeprazole OTC (over the counter) at a $5 copayment. Reimbursement to pharmacy providers for omeprazole OTC increased by $10.50 per claim, from $2.50 to a $13 dispensing fee. Initially, neither generic omeprazole prescription (Rx) nor brand omeprazole Rx was covered because omeprazole OTC was available in the same strength as the Rx products at a lower cost, but an omeprazole OTC shortage necessitated coverage of generic omeprazole Rx at a $10 copay. The objective of this study was to evaluate the long-term financial impact of a drug benefit policy change on a mid-size state employee health plan and its beneficiaries associated with the addition to coverage of omeprazole OTC. METHODS: The pharmacy claims database for the employee benefits division (EBD) was used to examine utilization and cost data for beneficiaries who received proton pump inhibitors (PPIs). Pharmacy claims for the 30-month period for dates of service from December 1, 2002, through May 31, 2005, were extracted from the database, yielding a preperiod of 15 months and a postpolicy change period of 15 months. RESULTS: In the 15-month postperiod, the number of PPI claims per member per month (PMPM) decreased by 3.9%, but the days of PPI therapy PMPM increased from 1.71 to 1.82 (6.4%). Price as measured by the allowed charge per day of drug therapy decreased from $4.25 to $2.74 (35.6%) despite an increase of $1.89 (76%) in the average dispensing paid per PPI claim to pharmacies, from $2.49 to $4.38. The average beneficiary copayment decreased by $0.50 (2.0%) per PPI claim, from $25.06 in the preperiod to $24.56 per claim in the postperiod. Therefore, the net heath plan cost for PPIs decreased by $2.20 PMPM (37.6%) during the 15-month postperiod, from $5.84 to $3.64 PMPM, producing savings of $4,207,350, or annualized savings of $3,365,880, in this employee benefit plan of 127,495 members. CONCLUSION: A change in policy to include coverage of omeprazole OTC and an increase in pharmacy reimbursement for omeprazole OTC resulted in 38% net savings to a state employee health plan. The large difference in drug acquisition cost between omeprazole OTC and the other Rx-only PPIs made it possible to implement a program intervention that provided financial benefit to pharmacists, beneficiaries, and the drug plan sponsor despite a 6% increase in PPI utilization.

An advanced pharmacy practice experience in application of evidence-based policy.

OBJECTIVE: To determine the impact of an advanced pharmacy practice experience (APPE) to develop skills needed to apply an evidence-based approach to population-level practice decisions. DESIGN: A 4-week evidence-based medicine APPE was implemented that included active-learning techniques and online learning modules, participation in state drug-policy committee meetings, and completion of an evidence-based medicine review for a specific drug agent or class. ASSESSMENT: Students' mean score on application of principles related to biostatistics and information mastery on posttests increased 15.8% from pretest to posttest. Students' mean score on a 22-question information mastery quiz was 90.8%. Mean scores for course evaluation components ranged from 4.8 to 5.0 on a 5-point Likert scale. All respondents indicated they would recommend the APPE to other students. CONCLUSIONS: An APPE that incorporated content from active drug-policy committees increased students' evidence-based medicine skills and enhanced their understanding of, appreciation for, and confidence in evidence-based practice.

Five-year examination of utilization and drug cost outcomes associated with benefit design changes including reference pricing for proton pump inhibitors in a state employee health plan.

BACKGROUND: The Arkansas State Employee Benefits Division (EBD) is a self-insured program comprising public school and other state employees, their spouses, and dependents. Previous research published in JMCP (2006) showed drug cost savings of $2.20 per member per month (PMPM; 37.6%) or annualized savings of $3.4 million associated with a benefit design change and coverage of the proton pump inhibitor (PPI) omeprazole over-the-counter (OTC) beginning in March 2004. On May 1, 2005, brand esomeprazole was excluded from coverage, with current users grandfathered for 4 months until September 2005. Reference pricing for PPIs, including esomeprazole but excluding generic omeprazole, was implemented on September 1, 2005, and the beneficiary cost share for all PPIs except generic omeprazole was determined from comparison of the PPI actual price to the $0.90 omeprazole OTC reference price per unit. OBJECTIVE: To examine PPI utilization and drug costs before and after (a) excluding esomeprazole from coverage (with grandfathering current users) and (b) implementing a therapeutic maximum allowable cost (TMAC), or reference-pricing benefit design, for the PPI class in a large state employee health plan with fairly stable enrollment of approximately 127,500 members in 2005 through 2008 and approximately 128,000 members in 2009 Q1. METHODS: The pharmacy claims database for the EBD was used to examine utilization and cost data for PPIs in a longitudinal analysis for the 61-month period from March 1, 2004, through March 31, 2009. Pharmacy claims data were compared for the period 14 months prior to esomeprazole exclusion (preperiod), 4 months during the esomeprazole exclusion (postperiod 1), and the ensuing 43 months of PPI reference pricing (postperiod 2). PPI cost and utilization data for the intervention group of approximately 127,500 beneficiaries were compared with a group of 122 self-insured employers with a total of nearly 1 million beneficiaries whose pharmacy benefits did not include reference pricing for PPIs. RESULTS: Despite 79% of existing esomeprazole users being grandfathered during the 4-month esomeprazole-exclusion period (postperiod 1), the share of omeprazole OTC claims increased from 35.2% to 42.5% (+ 7.3 percentage points) of all PPI claims, and esomeprazole claims decreased from 16.7% to 12.0% (-4.7 percentage points), with little change in the use of other PPIs. The average allowed charge (price) per day of PPI drug therapy decreased in postperiod 1 by 8.9% from $2.81 to $2.56, while utilization increased by 2.2% from 1.83 days PMPM to 1.87 days PMPM; the net plan cost PMPM decreased by $0.40 PMPM from $3.78 to $3.38 (-10.6%), representing a reduction in spending of $35,664 per month while the average member copayment per claim was essentially unchanged. In the 43 months of reference pricing in postperiod 2, PPI utilization was essentially unchanged at 1.82 days PMPM compared with the preperiod (1.83 days PMPM) and 2.7% lower than the esomeprazole-exclusion period (1.87 days PMPM); however, price (charge per day) decreased by 38.4% during refer- RESEARCH ence pricing to $1.73 from $2.81 in the preperiod and by 32.4% compared with $2.56 in the esomeprazole-exclusion period, despite an increase in the average pharmacy dispensing fee to $5.21 per PPI claim. Net plan cost decreased by $1.87 PMPM (49.5%) to $1.91 PMPM during reference pricing compared with the preperiod ($3.78 PMPM) and by $1.47 PMPM (43.5%) compared with the esomeprazole-exclusion period 1 ($3.38 PMPM). Beneficiary costs (copayment per claim) for PPIs decreased to $1.24 PMPM ($23.27 per claim) compared with the preperiod ($1.37 PMPM, $24.95 per claim) and compared with the esomeprazole-exclusion period ($1.40 PMPM, $25.06 per claim). The reductions in net plan costs represented lower plan spending for the 43 months of reference pricing (postperiod 2) of approximately $9.4 million or an average of approximately $219,500 per month compared with the preperiod or $7.9 million (approximately $183,900 per month) compared with the esomeprazole-exclusion period. Compared with a group of self-insured health plans without pharmacy benefit reference pricing of PPIs, the cost savings over the 43-month period from September 1, 2005, through March 31, 2009, were approximately $7.2 million or $1.31 PMPM. CONCLUSIONS: For this state employee health plan, the policy change that excluded esomeprazole from coverage but grandfathered current users was associated with a relatively small reduction in PMPM spending on PPIs compared with the subsequent policy change that applied reference pricing to the PPI class based on the price (drug cost plus dispensing fee) for omeprazole OTC. Over 43 months of reference pricing, net plan costs fell dramatically by 49.5% PMPM compared with the preperiod or decreased by 43.5% compared with the esomeprazole-exclusion period. While utilization was essentially unchanged compared with the 18 months before reference pricing, the average pharmacy dispensing fee per PPI claim increased, and beneficiary costs PMPM decreased.