Comparing the efficacy and side-effects of PDLASTA® (Pegfilgrastim) with PDGRASTIM® (Filgrastim) in breast cancer patients: a non-inferiority randomized clinical trial.

BACKGROUND: The objective of this study was to compare the efficacy and side effects of a single dose (Pegfilgrastim or PDL) or repeated six daily injections (Filgrastim or PDG) during chemotherapy courses in breast cancer patients in a non-inferiority clinical trial. METHODS: In this randomized clinical trial, 80 patients were recruited and allocated randomly to two equal arms. In one group, a single subcutaneous dose of PDL was injected the day after receiving the chemotherapy regimen in each cycle. The second arm received a subcutaneous injection of PDG for six consecutive days in each cycle of treatment. The side effects of GCF treatment and its effect on blood parameters were compared in each cycle and during eight cycles of chemotherapy. RESULTS: Hematologic parameters showed no significant differences in any of the treatment courses between the two study groups. The comparison of WBC (p = 0.527), Hgb (p = 0.075), Platelet (p = 0.819), Neutrophil (p = 0.575), Lymphocyte (p = 705) and ANC (p = 0.675) changes during the eight courses of treatment also revealed no statistically significant difference between the two study groups. Side effects including headache, injection site reaction and muscle pain had a lower frequency in patients receiving PDL drugs. CONCLUSION: It seems that PDL is non-inferior in efficacy and also less toxic than PDG. Since PDL can be administered in a single dose and is also less costly, it can be regarded as a cost-effective drug for the treatment of chemotherapy-induced neutropenia. TRIAL REGISTRATION: IRCT20190504043465N1 , May 2019.

Biosimilar Uptake in Medicare Part B Varied Across Hospital Outpatient Departments and Physician Practices: The Case of Filgrastim.

OBJECTIVES: To examine the uptake of filgrastim-sndz (Zarxio), the first biosimilar to launch in the United States, in the Medicare Part B fee-for-service program from its launch in September 2015 to December 2017 and compare characteristics of patients and facilities that used filgrastim-sndz or originator filgrastim (Neupogen). METHODS: The 20% sample of Medicare Part B fee-for-service administrative claims data was used to extract information on claims for any filgrastim product between January 1, 2015 and December 31, 2017. RESULTS: The utilization of filgrastim-sndz in Medicare Part B increased sharply between January and August 2016, surpassing filgrastim by November 2017, contributing to a 30% decrease in overall spending on this drug since 2015. Uptake was faster and larger in physician practices compared with hospital outpatient departments. About 77% of patients receiving filgrastim-sndz were new users. Utilization patterns indicated that product selection occurred at the facility level, rather than being at the discretion of the prescribing physician or driven by patient characteristics. CONCLUSION: Uptake of biosimilar filgrastim in the Medicare Part B program occurred despite multiple challenges to the adoption of biosimilars in the US market, suggesting that substantial potential savings could be generated by improving biosimilar uptake. Our findings indicated that physician practices and hospital outpatient departments have distinctive biosimilar uptake patterns. Thus policy makers aiming to contain Medicare Part B spending might consider focusing on incentivizing biosimilar uptake among hospital outpatient departments.

Tbo-filgrastim versus filgrastim for stem cell mobilization and engraftment in autologous hematopoietic stem cell transplant patients: A retrospective review.

INTRODUCTION: Filgrastim, a granulocyte colony-stimulating factor, is commonly used in autologous hematopoietic stem cell transplants (HSCTs) to assist with peripheral blood progenitor cell (PBPC) collection and to support stem cell engraftment. In the United States, tbo-filgrastim is approved under its own Biologic License Application and is limited to a single indication excluding the HSCT population. METHODS: Approximately one year after a system-wide formulary change to tbo-filgrastim for all on- and off-label indications, our institution conducted an IRB-approved retrospective comparison of tbo-filgrastim to filgrastim in the autologous HSCT setting. The study included 71 patients who received an autologous HSCT from 1 January 2013 to 31 December 2016 with a documented administration of tbo-filgrastim or filgrastim. RESULTS: There were no statistically significant differences noted on CD34 + counts during stem cell mobilization, neutrophil engraftment, infection rates during the engraftment phase, nor duration of hospitalization during the engraftment phase. More patients in the tbo-filgrastim group received plerixafor per protocol resulting in more patients meeting their PBPC collection goal in one day with fewer collection days overall, a result potentially confounded by institutional protocol changes. Utilizing tbo-filgrastim offered an average cost savings per patient of $2664.26 ($1907.33 for PBPC mobilization and $756.93 for stem cell engraftment) when comparing dollars spent on granulocyte colony-stimulating factor products only. CONCLUSION: Tbo-filgrastim demonstrates comparable efficacy with a cost savings benefit compared to filgrastim for autologous PBPC mobilization and stem cell engraftment.

Regulatory and Clinical Experiences with Biosimilar Filgrastim in the U.S., the European Union, Japan, and Canada.

Biosimilar filgrastims are primarily indicated for chemotherapy-induced neutropenia prevention. They are less expensive formulations of branded filgrastim, and biosimilar filgrastim was the first biosimilar oncology drug administered in European Union (EU) countries, Japan, and the U.S. Fourteen biosimilar filgrastims have been marketed in EU countries, Japan, the U.S., and Canada since 2008, 2012, 2015, and 2016, respectively. We reviewed experiences and policies for biosimilar filgrastim markets in EU countries and Japan, where uptake has been rapid, and in the U.S. and Canada, where experience is rapidly emerging. U.S. regulations for designating biosimilar interchangeability are under development, and such regulations have not been developed in most other countries. Pharmaceutical substitution is allowed for new filgrastim starts in some EU countries and in Canada, but not Japan and the U.S. In EU countries, biosimilar adoption is facilitated with favorable hospital tender offers. U.S. adoption is reportedly 24%, while the second filgrastim biosimilar is priced 30% lower than branded filgrastim and 20% lower than the first biosimilar filgrastim approved by the U.S. Food and Drug Administration. Utilization is about 60% in EU countries, where biosimilar filgrastim is marketed at a 30%-40% discount. In Japan, biosimilar filgrastim utilization is 45%, primarily because of 35% discounts negotiated by Central Insurance and hospital-only markets. Overall, biosimilar filgrastim adoption barriers are small in many EU countries and Japan and are diminishing in Canada in the U.S. Policies facilitating improved U.S. adoption of biosimilar filgrastim, based on positive experiences in EU countries and Japan, including favorable insurance coverage; larger price discount relative to reference filgrastim pricing; closing of the "rebate trap" with transparent pricing information; formal educational efforts of patients, physicians, caregivers, and providers; and allowance of pharmaceutical substitution of biosimilar versus reference filgrastim, should be considered. IMPLICATIONS FOR PRACTICE: We reviewed experiences and policies for biosimilar filgrastims in Europe, Japan, Canada, and the U.S. Postmarketing harmonization of regulatory policies for biosimilar filgrastims has not occurred. Acceptance of biosimilar filgrastims for branded filgrastim, increasing in the U.S. and in Canada, is commonplace in Japan and Europe. In the U.S., some factors, accepted in Europe or Japan, could improve uptake, including acceptance of biosimilars as safe and effective; larger cost savings, decreasing "rebate traps" where pharmaceutical benefit managers support branded filgrastim, decreased use of patent litigation/challenges, and allowing pharmacists to routinely substitute biosimilar for branded filgrastim.

A multi-center pragmatic, randomized, feasibility trial comparing standard of care schedules of filgrastim administration for primary febrile neutropenia prophylaxis in early-stage breast cancer.

INTRODUCTION: The most effective duration of filgrastim as primary febrile neutropenia (FN) prophylaxis in early breast cancer (EBC) patients is unknown. Despite significant differences in cost and toxicity, no prospective trial has been performed to optimize practice. We assessed the feasibility of using a novel pragmatic trial model to compare the most commonly used schedules of filgrastim. METHODS: Early breast cancer patients receiving chemotherapy were randomized to 5, 7, or 10 days of filgrastim as primary FN prophylaxis. The trial methodology integrated broad eligibility criteria, simply defined endpoints, an integrated consent model incorporating oral consent, and web-based randomization in the clinic. Feasibility was reflected through a combination of primary endpoints including patient and physician engagement (if > 50% of appropriate patients approached agree to participate, and if > 50% of physicians approached patients for the study). Secondary endpoints included the first occurrence rates of FN, treatment-related hospital admission, or chemotherapy dose reductions/delays/discontinuation. RESULTS: From May 2015 to August 2016, 142/149 (95.3%) patients approached agreed to participate and were randomized. Seventeen of 24 (70.8%) medical oncologists approached and randomized patients. The 142 patients received a total of 495 cycles of chemotherapy. Aggregate incidences of a first event by patient were FN (8/142, 5.6%), treatment-related hospitalization (6/142, 4.2%), chemotherapy discontinuation (7/142, 4.9%), chemotherapy delays (5/142, 3.5%), and chemotherapy dose reduction (18/142, 12.7%). Overall, 31.7% (45/142) of patients and 9.0% (45/495) of chemotherapy cycles were associated with one of these first events. CONCLUSION: This study met its feasibility endpoints. This novel pragmatic trial approach offers a means of comparing standard of care treatments in a practical and cost-effective manner. The trial will now be expanded to compare rates of FN between the three filgrastim schedules. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02428114.

Cost-effectiveness analysis of dose-dense versus standard intravenous chemotherapy for ovarian cancer: An economic analysis of results from the Gynecologic Oncology Group protocol 262 randomized controlled trial.

OBJECTIVES: To determine the cost-effectiveness of dose-dense versus standard intravenous adjuvant chemotherapy for ovarian cancer using results from the no-bevacizumab cohort of the Gynecologic Oncology Group protocol 262 (GOG-262) randomized controlled trial, which reported a smaller absolute progression-free survival (PFS) benefit than the prior Japanese trial. METHODS: A three-state Markov decision model from a healthcare system perspective with a 21day cycle length and 28month time-horizon was used to calculate incremental cost-effectiveness ratio (ICER) values per progression-free life-year saved (PFLYS) using results from GOG-262. Costs of chemotherapy, complications, and surveillance were from Medicare or institutional data. PFS, discontinuation, and complication rates were from GOG-262. Time-dependent transition probabilities and within-cycle corrections were used. One-way and probabilistic sensitivity analyses were performed. RESULTS: The model produces standard and dose-dense cohorts with 84.3% and 68.3% progression event proportions at 28months, matching GOG-262 rates at the trial's median follow-up. With a median PFS of 10.3months after standard chemotherapy and a hazard ratio for progression of 0.62 after dose-dense therapy, the ICER for dose-dense chemotherapy is $8074.25 (95% confidence interval: $7615.97-$10,207.16) per PFLYS. ICER estimates are sensitive only to the hazard ratio estimate but do not exceed $100,000 per PFLYS. 99.8% of ICER estimates met a more stringent willingness-to-pay of $50,000 per PFLYS. The willingness-to-pay value at which there is a 90% probability of dose-dense treatment being cost-effective is $12,000 per PFLYS. CONCLUSIONS: Dose-dense adjuvant chemotherapy is robustly cost-effective for advanced ovarian cancer from a healthcare system perspective based on results from GOG-262.

Expanded access to cancer treatments from conversion to neutropenia prophylaxis with biosimilar filgrastim-sndz.

AIM: Biosimilar medicines offer significant cost-savings potential over their reference products, which can be re-allocated to provide access to other cancer treatments on a budget-neutral basis. METHODS: Simulation study using cost data for the USA under consideration of several prophylaxis patterns. RESULTS: Potential savings from conversion from reference filgrastim to biosimilar filgrastim-sndz are significant. These savings expand budget-neutral access to novel immunotherapies (obinutuzumab; pembrolizumab) or supportive care (filgrastim-sndz). CONCLUSION: The combination of biosimilar savings and expanded access increases the value of cancer care as the same supportive care is provided at lower cost, additional cancer care is enabled at no additional cost, and more patients will have access to cancer care.

Uptake and cost of biosimilar filgrastim among Medicare and Medicaid populations in 2015-2018.

BACKGROUND: The first biosimilar product filgrastim-sndz was approved by the FDA in 2015, but real-world evaluations of its uptake and cost in nationally representative populations are limited. OBJECTIVE: To evaluate the uptake and cost of filgrastim-sndz, relative to its originator filgrastim and alternative biologic tbofilgrastim, among Medicare and Medicaid populations. METHODS: Using the annually aggregated, product-level utilization and cost data of biologic and biosimilar filgrastim products in 2015-2018 from CMS drug spending data, total number of claims and costs for all 3 filgrastim products were identified and extracted for Medicare Part B, Part D, and Medicaid reimbursement. Annual average cost per claim and per beneficiary of individual filgrastim products were also extracted, and their annual growth rates were calculated. RESULTS: Three years after entering the US market, use of filgrastim-sndz increased to 49.1% and 46.0% of all filgrastim claims paid by Medicare Parts B and D, respectively, and to 38.7% of filgrastim Medicaid claims in 2018. Total cost for filgrastim-sndz also reached 42.8%, 41.8%, and 26.9% of all filgrastim products paid by Medicare Parts B and D and Medicaid, respectively. Significant reductions in average cost per claim for filgrastim-sndz in 2017 and 2018 were observed in Medicare Part B and Medicaid. CONCLUSIONS: Significant uptake of biosimilar filgrastim in Medicare and Medicaid programs occurred during the first 3 years of marketing. Policymakers may use the evidence to evaluate existing barriers and policies regarding biosimilar adoption. DISCLOSURES: No outside funding supported this work. The author has no conflicts of interest to disclose.

Efficacy and cost of G-CSF derivatives for prophylaxis of febrile neutropenia in lymphoma and multiple myeloma patients underwent autologous hematopoietic stem cell transplantation.

OBJECTIVES: To compare the efficacies and costs between pegfilgrastim and filgrastim prophylaxis for FN post-ASCT for lymphoma and multiple myeloma patients. METHODS: 43 patients who received pegfilgrastim (6 mg) were compared to a retrospective cohort of 129 patients that had received filgrastim post-ASCT. Hematopoietic recovery time, FN incidence and treatment costs were assessed and compared. RESULTS: The mean time to absolute neutrophil count engraftment was 8.72 ± 2.38 days for the prospective pegfilgrastim group and 9.87 ± 3.13 days for the retrospective filgrastim group (P = 0.027). The incidence of FN was 18.60% and 50.39% in prospective pegfilgrastim and retrospective filgrastim groups, respectively (P = 0.000). The mean cost of filgrastim was $617.22 ± 37.87, compared with $525.78 for pegfilgrastim (P = 0.032). DISCUSSION: Convenience, effectiveness, and safety of prophylaxis for FN in the prospective pegfilgrastim group were significantly improved compared to the retrospective filgrastim group in ASCT patients. CONCLUSION: Pegfilgrastim prophylaxis was more effective and convenient than filgrastim for FN prophylaxis in patients post-ASCT, especially for MM patients.

Economic modeling for the US of the cost-efficiency and associated expanded treatment access of conversion to biosimilar pegfilgrastim-bmez from reference pegfilgrastim.

Aims: For this economic analysis, we aimed to model: (1) the cost-efficiency of prophylaxis with biosimilar pegfilgrastim-bmez for chemotherapy-induced (febrile) neutropenia (CIN/FN) compared to reference pegfilgrastim, and (2) the expanded access to CIN/FN prophylaxis and anti-neoplastic treatment that could be achieved with biosimilar cost-savings on a budget-neutral basis.Methods: In a hypothetical panel of 20,000 cancer patients receiving CIN/FN prophylaxis and using the average sales price (ASP) for the second quarter of 2019 for reference pegfilgrastim, we: conducted an ex ante simulation from the payer perspective of the cost-savings of 10-100% conversion from reference to biosimilar pegfilgrastim-bmez using drug price discounting ranging from 10-35%; estimated the budget-neutral expanded access to biosimilar pegfilgrastim-bmez enabled by these cost-savings; and estimated the budget-neutral expanded access to anti-neoplastic treatment with pembrolizumab. The simulations were replicated using fourth quarter 2019 wholesale acquisition cost (WAC) for reference pegfilgrastim and biosimilar pegfilgrastim-bmez in a post facto analysis.Results: In ASP simulations, cost-savings of using pegfilgrastim-bmez over reference pegfilgrastim in a 20,000 patient panel range from $1.3 M (at 15% price discount) to $3 M (35%) at 10% conversion rate and from $6.4 M to $14.9 M, respectively, at 50% conversion. These savings could provide prophylaxis with pegfilgrastim-bmez to an additional 352 (15% discount) to 1,076 patients (35%) at 10% conversion or 1,764-5,384, respectively, at 50% conversion. Alternatively, savings could be reallocated for anti-neoplastic treatment with pembrolizumab to 3 (15% discount) to 9 (35%) patients at 10% conversion or 19-45, respectively, at 50% conversion. When utilizing WAC, cost-savings range from $4.6 M (10% conversion) to $23.1 M (50%) which could provide pegfilgrastim-bmez to an additional 1,174 (10% conversion) to 5,873 patients (50%).Conclusions: Prophylaxis with biosimilar pegfilgrastim-bmez increases the value of cancer care by generating significant cost-savings that could be reallocated to provide expanded access to CIN/FN prevention and anti-neoplastic therapy on a budget-neutral basis.

Biosimilar Uptake in Academic and Veterans Health Administration Settings: Influence of Institutional Incentives.

OBJECTIVE: To compare uptake in the ordering of biosimilars at a Veterans Affairs Medical Center (VAMC) to that at an academic medical center, where institutional incentives for infused medications differ. METHODS: We performed a cross-sectional study of medical record data and estimated institutional financial incentives at 2 medical centers in Philadelphia: 1) the University of Pennsylvania Health System (UPHS), and 2) the local VAMC. All ordering events for filgrastim or infliximab products were quantified over time and stratified according to product (biosimilar versus reference product) and center. Financial incentives to the institutions over time were determined based on actual drug costs for the VAMC and average sales prices (ASPs) and Medicare Part B reimbursement rates for UPHS. RESULTS: There were 15,761 infusions of infliximab at UPHS, of which 99% were for the reference product. There was a sharper decline in the use of reference products at the VAMC; 62% of the 446 infliximab infusions ordered at the VAMC were for the reference product. ASPs were consistently lower for biosimilar infliximab products, but the estimated institutional financial incentives remained similar over time for biosimilar and reference infliximab at UPHS. At the VAMC, the costs for 100-mg vials of reference infliximab and infliximab-abda were $623.48 and $115.58, respectively: a $507.90 (81%) savings per vial. CONCLUSION: The uptake of infliximab biosimilars has been slow at an academic medical center compared to a nearby VAMC, where financial savings are realized by the institution from its use. Slow adoption of biosimilar medications may impact the rates of decline in costs.

Healthcare costs among patients with hemophilia A treated with factor replacement or bypassing agents.

Objective: To assess real-world costs for patients with hemophilia A treated with bypassing agents versus factor VIII (FVIII) replacement. Methods: Claims data from a large US health insurer during 1 January 2006-30 September 2014 were used for analysis. Treated patients with hemophilia A were identified based on ≥1 medical claim with a diagnosis code for hemophilia A (ICD-9-CM 286.0) and ≥1 medical or pharmacy claim for bypassing therapy and/or FVIII replacement during 1 January 2007-31 August 2014. The bypassing therapy cohort comprised patients with ≥1 claim for bypassing therapy; all others were assigned to the factor replacement therapy cohort. Post-index hemophilia-related costs were computed as combined health plan plus patient paid amounts for medical claims with hemophilia A diagnosis code or hemophilia therapy procedure code (bypassing therapy, FVIII replacement therapy, desmopressin, antifibrinolytic therapy), as well as pharmacy claims for hemophilia therapy. Results: The study sample represented 580 patients: 50 (8.6%) in the bypassing therapy cohort (mean age: 38.5 years; mean post-index period: 2.1 years) and 530 (91.4%) in the factor replacement therapy cohort (mean age: 29.3 years; mean post-index period: 2.7 years). Compared with the factor replacement therapy cohort, mean per-patient-per-month hemophilia-related total costs were 4.8-fold higher in the bypassing therapy cohort ($57,232 vs. $11,899), comprising 4.4-fold higher medical costs ($45,911 vs. $10,352) and 7.3-fold higher outpatient pharmacy costs ($11,321 vs. $1547). Conclusions: Patients with hemophilia A treated with bypassing agents between 2007 and 2014 incurred substantially higher monthly hemophilia-related medical and pharmacy costs than patients treated only with FVIII replacement.

Patient-Administered Biologic and Biosimilar Filgrastim May Offer More Affordable Options for Patients with Nonmyeloid Malignancies Receiving Chemotherapy in the United States: A Budget Impact Analysis from the Payer Perspective.

BACKGROUND: Granulocyte colony-stimulating factors (G-CSFs) are often administered to reduce the incidence, severity, and duration of febrile neutropenia (FN) in chemotherapy patients. Tbo-filgrastim and filgrastim-sndz represent a follow-on biologic and a biosimilar version, respectively, of the short-acting G-CSF filgrastim with comparable efficacy and safety. OBJECTIVE: To estimate the budget impact of increasing use of patient-(home-) administered tbo-filgrastim and filgrastim-sndz from a U.S. payer perspective. METHODS: An interactive budget impact model was developed to estimate the changes in drug cost associated with projected increases in the market share of tbo-filgrastim from 5% to 10% and of filgrastim-sndz from 10% to 12% (with a corresponding decrease in filgrastim market share from 85% to 78%) for a 1 million-member health plan among patients with nonmyeloid malignancies receiving chemotherapy with a high risk of FN. Patient self-administration at home was assumed for 20% of patients receiving short-acting G-CSF treatment; all products were purchased through the patient's pharmacy benefit and were assumed to have tier 3 formulary status with a patient copay of $54 per prescription. Base-case data were derived from publicly available resources. The total plan budget impact was calculated using a 1-year time horizon, along with the differences in per member per month and per member per year (PMPY) costs between the current and future scenarios. RESULTS: The effective annual per-patient drug cost to the plan totaled between $16,961 and $27,199, depending on dosage and packaging, for tbo-filgrastim; between $16,216 and $26,015 for filgrastim-sndz; and between $19,134 and $30,663 for filgrastim. The estimated total annual plan cost associated with patient-administered short-acting G-CSFs was $53,298,217 (PMPY = $53.30) in the current scenario and $52,828,832 (PMPY = $52.82) in the future scenario. Cost savings totaled $469,385 (PMPY = $0.48). The model was most sensitive to changes in the percentage of patients self-administering G-CSF at home and to the wholesale acquisition cost for filgrastim. CONCLUSIONS: The effective annual plan per-patient drug costs for tbo-filgrastim and filgrastim-sndz were 11% and 15% lower than filgrastim, respectively. The present analysis estimated an annual U.S. health plan cost savings approaching $0.5 million following increases in market shares of approximately 5% for tbo-filgrastim and 2% for filgrastim-sndz. DISCLOSURES: This study was sponsored by Teva Branded Pharmaceutical Products R & D, which participated in the study design, data interpretation and analysis, the writing of the report, and the decision to submit. Aventine Consulting received consulting fees from Teva Pharmaceuticals and developed the cost model and provided data analysis support. Trautman and James are employed by Aventine Consulting. Szabo and Tang are employed by Teva Pharmaceuticals.

A Retrospective Comparative Study of Different Methods of Blood Management in Total Knee Replacement.

Perioperative blood management is essential to minimize allogeneic blood transfusion in total knee replacement. The effect of preoperative administration of erythropoietin, intraoperative cell saver, tranexamic acid, and restrictive transfusion strategies on allogeneic transfusion is studied in total knee replacement. A retrospective comparative study of 106 patients who underwent total knee replacement in different time periods was performed. Group A (n 1 = 45) underwent restrictive strategies of transfusion between 2009 and 2010. Group B (n 2 = 24) includes patients where erythropoietin of either 10.000 IU or 20.000 IU was given preoperatively. Patients of Group C (n 3 = 21) underwent autologous washed erythrocytes transfusion through a cell saver. Lastly, in Group D (n 4 = 15) tranexamic acid dose of 1 gr IV was given intraoperatively. The preoperative and discharge hemoglobin together with total units of blood transfusion and creatinine levels was studied. Tranexamic acid noted the least units of blood transfusion (mean = 0.82 units/patient, p < 0.001, CI 95%) in contrast to the two regimens of erythropoietin (1.16 units/patient) OrthoPAT (1.43 units/patient) and restrictive strategies (1.92 units/patient). The mean preoperative hemoglobin was 13.37 g/dL with no statistical difference among the groups of patients. The postoperative mean hemoglobin was 10.59 with no statistical difference among the groups of patients too. Additionally, the mean creatinine level was 0.93 mg/dL; however, no statistical difference among the groups of patients was noted. Finally, tranexamic acid seemed to be the most cost-effective regime. In our study, tranexamic acid proved its superiority concerning the postoperative blood transfusion on patients undergoing total knee replacement, in comparison with the other existing methods of perioperative blood management. This is a Level III, retrospective comparative study.

Physicians' preferences towards coagulation factor concentrates in the treatment of Haemophilia with inhibitors: a discrete choice experiment.

This study sought to identify attributes of treatment important to haematologists in making their decisions regarding optimal care for inhibitor patients in the United States. A conjoint analysis using a discrete choice experiment was conducted to elicit factors that are most important to haematologists. Twelve product attributes were chosen based on published literature and expert opinion: risk of human viral infections, possibility that the titre of the inhibitor may rise, reduction in the likelihood of dose-related thromboembolic events, the number of infusions required to stop haemorrhage, infusion preparation time, infusion time, infusion volume, time required to stop bleeding, time required to alleviate pain, prophylaxis use, ability to undergo major surgery and cost of medications. Thirty haematologists completed the questionnaires via face-to-face interviews at a scientific meeting in April 2006. Data were analysed using a multinomial logit model to obtain the relative importance of each attribute. Responding haematologists had considerable experience in treating haemophilia patients with inhibitors (average : 13 +/- 9 years). 'Time required to stop bleeding' was the most important factor affecting treatment decisions [relative importance (RI) = 16.3%]. Physicians also preferred treatments that resulted in quick pain relief [RI = 12.9%], reduced the possibility that the titre of inhibitor may rise [RI = 12.8%], required fewer number of infusions to stop a haemorrhage [RI = 12.7%] and reduced the risk of human viral infection [RI = 10.8%]. This study revealed that certain clinical outcomes attributes are the most preferred and important. These findings can assist decision makers in their assessments of optimal first-line care.

Cost-savings for biosimilars in the United States: a theoretical framework and budget impact case study application using filgrastim.

BACKGROUND: Biosimilars can directly reduce the cost of treating patients for whom a reference biologic is indicated by offering a highly similar, lower priced alternative. We examine factors related to biosimilar regulatory approval, uptake, pricing, and financing and the potential impact on drug expenditures in the U.S. METHODS: We developed a framework to illustrate how key factors including regulatory policies, provider and patient perception, pricing, and payer policies impact biosimilar cost-savings. Further, we developed a budget impact cost model to estimate savings from filgrastim biosimilars under various scenarios. The model uses publicly available data on disease incidence, treatment patterns, market share, and drug prices to estimate the cost-savings over a 5-year time horizon. RESULTS: We estimate five-year cost savings of $256 million, of which 18% ($47 million) are from reduced patient out-of-pocket costs, 34% ($86 million) are savings to commercial payers, and 48% ($123 million) are savings for Medicare. Additional scenarios demonstrate the impact of uncertain factors, including price, uptake, and financing policies. CONCLUSIONS: A variety or interrelated factors influence the development, uptake, and cost-savings for Biosimilars use in the U.S. The filgrastim case is a useful example that illustrates these factors and the potential magnitude of costs savings.

A comparison of the effect of xinruibai versus filgrastim on hematopoietic reconstruction after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: To compare the effect of xinruibai (Pegfilgrastim) and filgrastim injections on white blood cell and platelet (PLT) recovery, adverse events, post-operative complications, and cost effectiveness after allogeneic hematopoietic stem cell transplantation (allo-HSCT). METHODS: Children who underwent allo-HSCT at our hospital from January 2014 to May 2017 due to thalassemia major, aplastic anemia, leukemia, and mucopolysaccharidosis were included. Among the children, 53 received xinruibai injections and 33 received filgrastim injections. RESULTS: There were no significant differences in the average time to neutrophil and platelet recovery, the incidence of post-operative complications after allo-HSCT, the number of red blood cell and PLT infusions, or the incidence of adverse events related to the injection between two groups (P >  0.05). The pain score was 3.06 (SD 0.41) for the xinruibai group and 25.18 (SD 6.22) for the filgrastim group, indicating significant differences between the two groups (P <  0.001). No difference was found in the hospitalization cost. The cost of the granulocyte-colony stimulating factor (G-CSF) was 257.11 ± 61.87 Euro in the xinruibai group and 214.79 ± 0.00 Euro in the filgrastim group, showing significant difference (P <  0.001). CONCLUSIONS: Xinruibai injection was more convenient, simple, effective, and safer than filgrastim.

Conversion from Filgrastim to Tbo-filgrastim: Experience of a Large Health Care System.

BACKGROUND: In 2008, tbo-filgrastim was approved as a biosimilar in Europe and then approved in the United States by the FDA in 2012 as a biologic product with 1 similar indication to filgrastim. Because tbo-filgrastim was less expensive than filgrastim, and clinical information and expert opinion supported similarity, the Pharmacy & Therapeutics Committee of a large health care system approved tbo-filgrastim as the preferred granulocyte-colony stimulating factor (G-CSF) product in March 2014. OBJECTIVES: To (a) assess the use of filgrastim and tbo-filgrastim products by comparing baseline characteristics, setting of care, indication for use, and payer type and (b) understand potential barriers of conversion to tbo-filgrastim. METHODS: A retrospective evaluation of filgrastim and tbo-filgrastim use was conducted on all patients (N = 204) who received the drugs between July 2015 and December 2015 at the 2 largest hospitals in the health system. Baseline characteristics, indication requiring use of filgrastim or tbo-filgrastim, setting of care, and payer information were collected from electronic medical records, and descriptive analyses were conducted. RESULTS: Overall, G-CSFs were administered to 204 patients for 261 episodes of care (filgrastim and tbo-filgrastim were used in 65 and 196 episodes of care, respectively). Baseline characteristics were similar between the 59 patients who received filgrastim and the 174 patients who received tbo-filgrastim. G-CSF was primarily used in the inpatient setting (163 episodes of care, 63%) with 90% of patients using tbo-filgrastim. In the outpatient setting (98 episodes of care, 38%), filgrastim and tbo-filgrastim were each used by 50% of patients. Tbo-filgrastim was the preferred G-CSF by clinical providers for all indications, except for stem cell mobilization, where filgrastim use was higher (55% vs. 45% of 71 episodes of care). In the outpatient setting, analysis by payers showed that the majority of patients on commercial plans were using filgrastim (58%), while half of Medicare patients were using filgrastim (50%, n = 12). Twelve patients were self-paid, and all were using tbo-filgrastim. Subgroup analysis by hospital showed differences in utilization patterns. CONCLUSIONS: Although tbo-filgrastim was the preferred G-CSF in our formulary, 29% of patients continued to receive filgrastim. Conversion to tbo-filgrastim has been largely successful, but extra steps may be needed to achieve full conversion to biosimilars. DISCLOSURES: No outside funding supported this study. Agboola was employed by Partners Healthcare at the time of the study. The authors have nothing to disclose. Study concept and design were contributed equally by Agboola and Reddy. Agboola collected the data, and data interpretation was performed by both authors. The manuscript was written primarily by Agboola, with assistance from Reddy. Both authors revised the manuscript.

Comparison of transplant outcomes and economic costs between biosimilar and originator filgrastim in allogeneic hematopoietic stem cell transplantation.

From January 2012 to September 2015, 49 patients received biosimilar filgrastim (BF) after allogeneic bone marrow transplantation (BMT, n = 31) or peripheral stem cell transplantation (PBSCT, n = 18) in our institution. To evaluate the clinical impact of BF on transplant outcomes of these patients, we compared hematological recovery, overall survival (OS), disease-free survival (DFS), transplantation-related mortality (TRM), cumulative incidence of relapse (CIR), and acute and chronic graft-versus-host disease (GVHD) with those of control patients who received originator filgrastim (OF) after BMT (n = 31) or PBSCT (n = 18). All cases were randomly selected from a clinical database in our institution. In both the BMT and PBSCT settings, neutrophil recovery (17 vs. 19 days in BMT; 13 vs. 15 days in PBSCT) and platelet recovery (27 vs. 31 days in BMT; 17 vs. 28 days in PBSCT) were essentially the same between BF and OF. They were also comparable in terms of OS, DFS, TRM, CIR, and the incidence of acute GVHD and chronic GVHD. On multivariate analysis, the use of BF in both BMT and PBSCT was not a significant factor for adverse transplant outcomes. Although BF significantly reduced filgrastim costs in both BMT and PBSCT, total hospitalization costs were not significantly different between BF and OF.

Cluster randomized controlled trial of TIA electronic decision support in primary care.

OBJECTIVE: To test if TIA/stroke electronic decision support in primary care improves management. METHODS: Multicenter, single-blind, parallel-group, cluster randomized, controlled trial comparing TIA/stroke electronic decision support guided management with usual care. Main outcomes were guideline adherence and 90-day stroke risk. Secondary outcomes were cerebrovascular/vascular/death/adverse events, cost, and user feedback. Main analysis was logistic regression with a normal random effect for clusters using a generalized linear mixed model. RESULTS: Twenty-nine clinics were randomized to intervention, 27 to control, recruiting 172 and 119 eligible patients. More intervention patients received guideline-adherent care (131/172; 76.2%) than control patients (49/119; 41.2%) (adjusted odds ratio [OR] 4.57; 95% confidence interval [CI] 2.39-8.71; p < 0.001). Ninety-day stroke occurred in 2/172 (1.2%) intervention and 5/119 (4.2%) control patients (OR 0.27; 95% CI 0.05-1.41; p = 0.098). Ninety-day TIA or stroke occurrence was lower in the intervention group, 4/172 (2.3%) compared to 10/119 (8.5%) control (adjusted OR 0.26; 95% CI 0.70-0.97; p = 0.045). Fewer vascular events/deaths occurred in intervention, 6/172 (3.5%), than in control patients, 14/119 (11.9%) (adjusted OR 0.27; 95% CI 0.09-0.78; p = 0.016). Treatment cost ratio of 0.65 (95% CI 0.47-0.91; p = 0.013) favored the intervention without increased adverse events. Clinician feedback was positive. CONCLUSION: Primary care use of the TIA/stroke electronic decision support tool improves guideline adherence, safely reduces treatment cost, achieves positive user feedback, and may reduce cerebrovascular and vascular event risk following TIA/stroke. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that a primary care electronic decision support tool improves guideline adherence and might reduce 90-day stroke risk.