An integrated approach to evaluate different tetracycline derivatives for formulary decisions

Disclaimer In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose Stenotrophomonas maltophilia has emerged as a critical opportunistic pathogen associated with significant morbidity and mortality. Tetracycline derivatives have been recognized as alternative treatment options, but they have varied pharmacokinetic properties. An integrated approach to different tetracycline derivatives for formulary decisions is reported. Methods The minimum inhibitory concentration (MIC) data from clonally diverse bloodstream S. maltophilia isolates were examined, along with the pharmacokinetic profiles of 4 tetracycline derivatives, to predict achievable pharmacodynamic exposures with standard intravenous dosing regimens. Antimicrobial therapy was assessed using the ratio of daily drug acquisition cost relative to the ratio of the free-drug area under the time-concentration curve (fAUC) to the 90th percentile for minimum inhibitory concentration (MIC) values for isolates (fAUC/MIC90). Results In our analysis, minocycline had the greatest fAUC/MIC90. Doxycycline was the most financially preferred agent, as calculated using 2020 average wholesale price for base-case estimates of drug acquisition cost. Conclusion An integrated evaluation for antimicrobial formulary decision-making addressed local susceptibility data, pharmacokinetics, pharmacodynamics, dosing regimens, and drug acquisition costs. This comprehensive method is more objective than the conventional approach and warrants validation.

Cost-efficiency analysis of conversion from reference pegfilgrastim to its biosimilar (pegfilgrastim-jmdb) and expanded access to food and transportation support for Medicare/Medicaid patients within the CMS Oncology Care Model.

e18837 Background: The CMS Oncology Care Model (OCM) aims to improve quality of care and health outcomes in cancer centers at the same or lower cost. We performed cost-efficiency analyses of converting selected cancer patients (pts) from reference pegfilgrastim (PFG) to its biosimilar (PFG-jmdb); and simulated re-allocating savings to provide nutrition and transportation support to CMS beneficiaries within OCM. Methods: Incidence rates for breast, ovarian, lung, colorectal cancers and non-Hodgkin lymphoma were extracted from SEER, further stratified by age <65 (commercial insurance) or >65 (Medicare) adjusted for Medicare/Medicaid mix. Chemotherapy (CTX) rates were matched to tumor type; of these 19.4% were assumed to require PFG prophylaxis (PPX). Two models compared respectively prefilled syringe (PFS) and on-body injector (OBI) reference PFG to PFS PFG-jmdb. Cost inputs included Average Sales Price (ASP) 3Q20 for Medicare and National Average Drug Acquisition Cost (NADAC, estimated by wholesale acquisition cost (WAC)-3.9%) for Medicaid pts plus medication administration. Cost savings across various biosimilar conversion rates for CTX cycles 1-6 were translated into $100 units of healthy food or medical transportation. Results: In 2020, biosimilar conversion for the estimated 31,210 Medicare and 1,722 Medicaid pts in the 5 tumor types needing PFG PPX yielded savings of up to ̃$19M (Medicare) and ̃$20M (Medicaid). These savings could have provided a monthly $100 food or transportation check to at least 24,716 Medicare or 33,630 Medicaid pts for 6 months. Conclusions: Savings from biosimilar conversion can be re-allocated on a budget neutral basis to food and transportation support to pts with such needs. This achieves the dual OCM aim of reducing drug budgets while enhancing patient-centric support services.[Table: see text]

Abstract 14615: Empagliflozin Provides More Value for Money Than Oral Semaglutide for Prevention of Cardiovascular Mortality in Patients With Type 2 Diabetes Mellitus

Introduction: The AHA 2020 strategic goal of reducing CV mortality by 20% was partially achieved (15% reduction 2011-2019). Empagliflozin, an inhibitor of sodium-glucose cotransporter 2 inhibitor and oral semaglutide, the first oral glucagon-like peptide 1 receptor agonist, both significantly reduce the incidence of cardiovascular mortality (CVM) in patients with type 2 diabetes (DM) and established CVD. However, the addition of either drug to current diabetes treatment regimens may impose a significant burden on healthcare systems. Hypothesis: Empagliflozin provides more value for money than oral semaglutide for the prevention of CVM in patients with DM. Methods: We calculated the cost needed to treat (CNT) to prevent one case of CVM using either drug, by multiplying the annualized number needed to treat (NNT) to prevent one event, by the annual cost of the therapy. Efficacy estimates were extracted from published randomized controlled trials (RCT) data. We performed a sensitivity analysis to mitigate the primary differences between the RCTs and other uncertainties. Drug costs were calculated as 75% of the US National Average Drug Acquisition Cost listing in June 2020. Results: The annualized NNT of empagliflozin in EMPA-REG-OUTCOME was 141 (95% CI: 104-230) versus 140 (95% CI: 98-893) for oral semaglutide in PIONEER 6, while the corresponding annual costs are $4,572 versus $6,680. Therefore, the CNT of empagliflozin was $644,652 ($475,488-$1,051,560) compared to $935,200 (95% CI: $654,640-$5,965,240) with oral semaglutide. The lower CNT of empagliflozin was confirmed in a sensitivity analysis. Conclusions: The annualized NNT of empagliflozin and oral semaglutide prescribed for the prevention of CVM in patients with T2DM and established CVD is similar. Therefore, the lower cost of empagliflozin results in a lower CNT and better value for money.

Abstract 13680: Icosapent Ethyl Therapy for Patients With an Established Cardiovascular Disease Provides Significantly More Value for Money Than When Prescribed as Primary Prevention

Introduction: Icosapent ethyl is currently the only drug approved for the prevention of major adverse cardiovascular events (MACE) in patients with hypertriglyceridemia, who are already on statin therapy. The approved use is both for secondary prevention in patients with established cardiovascular disease (CVD) or primary prevention for patients with diabetes and multiple risk factors. Despite its’ proven clinical benefits, the addition of icosapent ethyl to patient’s current treatment regimens may impose a significant cost burden on healthcare systems. Hypothesis: Prioritizing icosapent ethyl therapy for patients with an established CVD may provide significantly more value for money than when prescribed as primary prevention. Methods: We performed an analysis of the cost required for icosapent ethyl per achieved outcome when prescribed either for primary or for secondary prevention of MACE. The cost needed to treat (CNT) to prevent one MACE in the REDUCE-IT trial was estimated by multiplying the annualized number needed to treat to prevent one event, by the annual cost of therapy. The market price of icosapent ethyl in the US was estimated as 75% of the US national average drug acquisition cost listing. Results: In the REDUCE-IT population, the figured CNT of Icosapent ethyl provided as primary prevention was $874,500 (95% CI: $349,800-∞) vs. $206,965 (95% CI: $160,325-$294,415) for secondary prevention; P<0.001. Conclusions: The CNT for patients receiving the drug for primary prevention of MACE was four-fold higher than when provided as secondary prevention. Our findings suggest that icosapent ethyl therapy for patients with an established CVD provides significantly more value for money.

Abstract 14730: Oral Semaglutide Provides Less Value for Money Than Subcutaneous Semaglutide for the Prevention of Major Adverse Cardiovascular Events, but Significantly More Value for Money for the Prevention of Cardiovascular Mortality

Introduction: Semaglutide, a subcutaneous Glucagon-Like Peptide-1 receptor agonist, reduces the risk of major adverse cardiovascular events (MACE) in patients with Type 2 diabetes mellitus (T2DM). An oral version of semaglutide is now available, and patients may prefer it over a subcutaneous injection. The value for money of the oral version for the prevention of MACE is not clear. Hypothesis: Oral semaglutide provides less value for money than subcutaneous semaglutide for the prevention of MACE, but more value for money for the prevention of the single endpoint of cardiovascular mortality (CVM). Methods: We calculated the cost needed to prevent (CNT) one MACE, by multiplying the one-year number needed to treat to prevent one event, by the annual cost of the therapy. Efficacy estimates were extracted from published RCT data. The CNT to prevent one event of the single endpoint of CVM was analyzed as a secondary outcome. We performed a sensitivity analysis to mitigate primary differences between the RCTs. Drug costs were calculated as 75% of the US National Average Drug Acquisition Cost listing in June 2020. Results: The CNT to prevent one MACE with subcutaneous semaglutide in SUSTAIN-6 is $641,823 ($402,021-$3,533,533) compared to $855,040 (95% CI: $420,840-∞) with oral semaglutide in PIONEER 6. The lower cost of subcutaneous semaglutide was confirmed in a sensitivity analysis simulating the effects of the drugs in both RCTs. The CNT to prevent one CVM with semaglutide is $16,342,560 ($2,020,704.00-∞) compared to $1,315,720 (95% CI: $921,004-$8,392,414) with oral semaglutide. Conclusions: Subcutaneous semaglutide prescribed for the prevention of MACE in patients with T2DM is moderately cost-saving compared to oral semaglutide for the same purpose. However, for the prevention of CVM, the oral version provides significantly better economic value.

Pharmaceutical pricing benchmarks: governmental versus private sector

Purpose: To explore the best pricing benchmark for workers’ compensation drugs reimbursement at retail pharmacies. Materials & methods: We used California workers’ compensation system (CAWCS) total cost of pharmacy dispensed medications (2017–2019) as a proxy to estimate drug prices using alternative pricing mechanism fee schedules. Results: CAWCS paid 65.6% of the average wholesale price (AWP), 104.1% of Medi-Cal, 122.1% of the wholesale acquisition cost (WAC), 140.1% of the national average drug acquisition cost (NADAC), and 253.5% of the federal upper limit. In addition, we found the AWP-based formulas: CAWCS = AWP - 34.4%, Medi-Cal = AWP - 36.9%, WAC = AWP - 46.3%, NADAC = AWP - 53.2%, and federal upper limit = AWP - 74.1%. We found that AWP: 50% for generics and AWP - 18.2% for brands are the lowest paying formulas. The estimated median cost savings were $8.7 million (by adapting 97% of the WAC) and $9.5 million (by adapting the NADAC) across all states. Conclusion: NADAC was the best pricing benchmark for reimbursement of pharmacy dispensed drugs.

Efficacy and Safety of Nivestim Versus Neupogen for Mobilization of Peripheral Blood Stem Cells for Autologous Stem Cell Transplantation

A retrospective cohort study was conducted in Singapore General Hospital to study the safety and efficacy of biosimilar granulocyte-colony stimulating factor (G-CSF) Nivestim for chemo-mobilization of stem cells for autologous stem cell transplant (autoSCT). All patients who underwent an autoSCT between January 2011 and December 2016 were screened for eligibility. A total of 194 patients were screened, and 131 were included. Nivestim was used in 65 patients and the originator G-CSF (Neupogen) in 66. Patient characteristics were similar between both arms except for chemo-mobilization regimen used (p < 0.0001). Mobilization success rates were found to be comparable, at 96.9% (Nivestim) and 97% (Neupogen). Adverse events rates were also similar. Median duration of G-CSF use and hospitalization were both found to be shorter in the Nivestim arm. Median drug acquisition cost per mobilization cycle was significantly lower in the Nivestim arm at $533.40 (range $213.40–$1280.20) as compared to $1261.90 (range $574–$2755.20) in the Neupogen arm (p < 0.0001). No difference was observed for neutrophil and platelet engraftment after autoSCT. Nivestim was found to be safe and non-inferior to Neupogen for chemo-mobilization of stem cells for autoSCT, and associated with lower cost and shorter length of hospitalization.

Reducing Hospitalizations: Institution of Outpatient Infusional EPOCH-Based Chemotherapy at a Safety Net Hospital

PURPOSE: EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin) -based chemotherapy is traditionally administered inpatient because of its complex 96-hour protocol and number of involved medications. These routine admissions are costly, disruptive, and isolating to patients. Here, we describe our experience transitioning from inpatient to outpatient ambulatory EPOCH-based chemotherapy in a safety-net hospital, associated cost savings, and patient perceptions. METHODS AND MATERIALS: Guidelines for chemotherapy administration and educational materials were developed by a multidisciplinary team of physicians, nurses, and pharmacists. Data were collected via chart review and costs via the finance department. Patient satisfaction with chemotherapy at home compared with hospitalization was measured on a Likert-type scale via direct-to-patient survey. RESULTS: From January 30, 2017, through January 30, 2018, 87 cycles of EPOCH-based chemotherapy were administered to 23 patients. Sixty-one ambulatory cycles (70%) were administered to 18 patients. Of 26 cycles administered in the hospital, 18 (69%) were the first cycle of treatment. Rates of inappropriate prophylactic antimicrobial prescription and laboratory testing were lower in the outpatient setting. Eight of nine patients surveyed preferred home chemotherapy to inpatient chemotherapy. Per-cycle drug costs were 57.6% lower in outpatients as a result of differences in the acquisition cost in the outpatient setting. In total, the transition to ambulatory EPOCH-based chemotherapy yielded 1-year savings of $502,030 and an estimated 336 days of avoided hospital confinement. CONCLUSION: Multiday ambulatory EPOCH-based regimens were successfully and safely administered in our safety-net hospital. Outpatient therapy was associated with significant savings through avoided hospitalizations and reductions in drug acquisition cost and improved patient satisfaction.

National cancer expenditure analysis in the United States Medicare population, 2013.

6647 Background: Cancer is the second leading killer in the United States, but there is no comprehensive analysis evaluating total cancer costs by cancer and treatment modality. Methods: Data from the 2013 inpatient (100%), outpatient (100%), and carrier (5%) Medicare Limited Data Set Standard Analytic Files were queried for claims filed for International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes for all cancer diagnoses. Claims associated with the ICD-9 codes for professional fees were analyzed by Current Procedure Terminology (CPT) code to determine resource allocation by disease. Outpatient oral chemotherapy costs were obtained from the National Average Drug Acquisition Cost database for 50 drugs used for cancer treatment in 2013. Results: $27.9 billion was spent on cancer treatment of which $12 billion (43%), $6.5 billion (23%), and $1.1 billion (4%) was allocated to professional, inpatient facility, and outpatient facility fees, respectively. Oral and hospital-based chemotherapy accounted for 17% ($4.7 billion) and 15% ($4.3 billion) of all cancer costs, respectively. Lung/thoracic cancer ($2.9 billion) had the highest total annual cost and multiple myeloma ($9,019, SD $19,962) is the most expensive cancers to treat annually per patient. Average out-of-pocket expenses are $470 (SD 287), which is 12% of the annualized per patient costs. Conclusions: In 2013, cancer accounted for only 5% of Medicare spending. Chemotherapy costs accounted for approximately a third of total spending and are likely to rise as innovation continues. Out-of-pocket spending can place a financial burden on cancer patients requiring more expensive treatments.

Creating value: Institution of outpatient infusional EPOCH-based chemotherapy at a safety-net hospital.

128 Background: EPOCH-based chemotherapy regimens are traditionally administered inpatient because they include a continuous 96-hour infusion. These admissions are costly, and disruptive to patients’ lives. We transitioned EPOCH-based chemotherapy regimens to an ambulatory infusion model at our safety-net hospital (Parkland Health and Hospital System, Dallas, TX), where patients visit the infusion center daily for 5 days. Methods: Guidelines for chemotherapy administration and educational materials were developed through a multidisciplinary collaboration with physicians, nursing, and pharmacy. Data were collected through chart review and the finance department. Project costs included purchase of portable infusion pumps and increasing outpatient infusion clinic capacity. Patient satisfaction with home infusions compared to hospitalization was measured on a Likert-type scale via direct-to-patient survey. Results: From 1/30/2017 through 1/30/2018, a total of 87 cycles of EPOCH-based chemotherapy were administered to 23 unique patients. 61 (70%) of these cycles were administered in the outpatient setting to 18 unique patients. There was a 58% reduction in drug costs in the outpatient setting due to lower drug acquisition cost. An estimated 336 days of hospital stay were avoided. There were no inappropriate prophylactic antimicrobial prescriptions and daily blood draws in the outpatient setting. 88% of survey responders reported > 3 (scale, 1 to 5) on a Likert-type scale for both overall experience with home infusions, and likelihood they would use home infusions again. No chemotherapy spills or extravasation occurred; 1 cycle was complicated by pump failure where chemotherapy was given at a slower rate than intended. Conclusions: Multiday EPOCH-based regimens were successfully and safely administered in an ambulatory setting at our safety net urban hospital. Patients reported satisfaction with the experience, and received less unnecessary interventions in the outpatient setting. Significant cost savings from avoided hospitalization and decreased drug acquisition cost were demonstrated.