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Rashid Kazerooni, 1 Ileana M Howard, 2, 3 Adrienne M Keener, 4, 5 Mark Bounthavong 6, 7 1Merz Pharmaceuticals, LLC, Raleigh, NC, 27615, USA; 2Rehabilitation Care Services, VA Puget Sound, Seattle, WA, USA; 3Department of Rehabilitation Medicine, University of Washington, Seattle, WA, USA; 4Department of Neurology, David Geffen School of Medicine, Los Angeles, CA, USA; 5Parkinson's Disease Research, Education, and Clinical Center, Greater Los Angeles Veterans Affairs Medical Center, Los Angeles, CA, USA; 6VA Health Economics Resource Center, VA Palo Alto Health Care System, Menlo Park, CA, USA; 7Department of Clinical Pharmacy, UCSD Skaggs School of Pharmacy & Pharmaceutical Sciences, SanDiego, CA, USACorrespondence: Rashid KazerooniAssociate Director, Health Economics and Outcomes Research, Merz Pharmaceuticals, LLC, 6601 Six Forks Road, Suite 430, Raleigh, NC, 27615, USATel +1.785.249.3233Email rashid.kazerooni@merz.comPurpose: This study sought to perform a real-world, long-term cost-minimization analysis for incobotulinumtoxinA (Xeomin®) versus onabotulinumtoxinA (Botox®), given the established non-inferiority when utilized at similar doses.Methods: The Department of Veterans Affairs (VA) and Department of Defense (DoD) national healthcare systems were included in this analysis. Real-world purchase data for incobotulinumtoxinA were used to estimate the direct drug costs between calendar years 2014 and 2019. Publicly available federal pharmaceutical prices (Federal Supply Schedule and Big 4) were used. The primary outcome was the difference in total direct costs nationally for incobotulinumtoxinA (real-world) versus having hypothetically utilized onabotulinumtoxinA (projected) for similar utilization. Sites utilizing ≥ 100 vials (of 100 Unit equivalents) of incobotulinumtoxinA annually were categorized as “major adopters”. IncobotulinumtoxinA 50 Unit vials were assumed to be an alternative to a 100 Unit vial of onabotulinumtoxinA for 50% of such vial purchases in the base case scenario to account for differences in wastage.Results: Over the six-year study time frame, 156 sites (76.8%) utilized incobotulinumtoxinA of the 203 total VA healthcare systems and DoD medical centers. Of these sites, 67 were major adopters for at least one year, with a mean of 3.4 years spent as a major adopter over the study period. Average annual savings per major adopter was $105,782. IncobotulinumtoxinA costs for all VA/DoD sites was $46.39 million for the six-year period versus a projected $71.92 million onabotulinumtoxinA cost—a total savings of $25.53 million (35.5% relative reduction). Approximately, 82.8% of savings stemmed from lower drug acquisition cost ($21.14 million) and 17.2% of savings ($4.39 million) was related to reduced wastage. It was estimated that a total of 9958 extra onabotulinumtoxinA 100 Unit vials would have been wasted during the six-year period, translating to the need for a 5.9% increase in vial purchases versus incobotulinumtoxinA.Conclusion: Meaningful cost savings were realized related to incobotulinumtoxinA adoption over a long-term time frame in the VA/DoD healthcare systems.Keywords: Xeomin, Botox, cost, federal, savings

Mai-Chi Hong1, Donald I Hsu1,2, Mark Bounthavong3,41Department of Pharmacy Practice and Administration, Western University of Health Sciences, Pomona, 2Department of Pharmacy, St Joseph Hospital, Orange, 3Department of Pharmacy, Veterans Affairs San Diego Healthcare System, San Diego, 4Department of Pharmacy Practice, University of California, San Diego, CA, USAAbstract: The management of infections caused by multidrug-resistant Gram-negative bacteria, particularly Pseudomonas aeruginosa, continues to be a significant challenge to clinicians. Ceftolozane/tazobactam is a novel antibacterial and β-lactamase-inhibitor combination that has shown appreciable activity against wild-type Enterobacteriaceae and potent activity against P. aeruginosa. Moreover, ceftolozane/tazobactam has not demonstrated cross-resistance to other antimicrobial classes, particularly those affected by extended-spectrum β-lactamases, AmpC β-lactamase, a loss in porin channels, or the overexpression of efflux pumps in P. aeruginosa. Ceftolozane/tazobactam has completed two Phase II clinical trials in complicated intra-abdominal and complicated urinary tract infections. A Phase III, multicenter, prospective, randomized, open-label study has been initiated to evaluate the safety and efficacy of ceftolozane/tazobactam versus piperacillin/tazobactam for the treatment of ventilator-associated pneumonia. A Medline search of articles from inception to May 2013 and references for selected citations was conducted. Data from abstracts presented at conferences were also appraised. This article reviews the antimicrobial, pharmacokinetic, and pharmacodynamic profile of ceftolozane/tazobactam, and discusses its potential role in therapy.Keywords: CXA-201, CXA-101, FR264205, Pseudomonas aeruginosa

Background: Rheumatoid arthritis (RA) is a chronic autoimmune disease that affects approximately 1.5 million people in the US. Tumour necrosis factor (TNF)-α inhibitors have been shown to effectively treat and maintain remission in patients with moderately to severely active RA compared with conventional agents. The high acquisition cost of TNF-α inhibitors prohibits access, which mandates economic investigations into their affordability. The lack of head-to-head comparisons between these agents makes it difficult to determine which agent is the most cost effective.Objective: This study aimed to determine which TNF-α inhibitor was the most cost-effective agent for the treatment of moderately to severely active RA from the US healthcare payer's perspective.Methods: A Markov model was constructed to analyse the cost utility of five TNF-α inhibitors (in combination with methotrexate [+MTX]) versus MTX monotherapy using Bayesian methods for evidence synthesis. The model had a cycle length of 3 months and an overall time horizon of 5 years. Transition probabilities and utility scores were based on published studies. Total direct costs were adjusted to year 2009 $US using the medical component of the Consumer Price Index. All costs and QALYs were discounted at a rate of 3% per year. Patient response to the different strategies was determined by the American College of Rheumatology (ACR)50 criteria. One-way and probabilistic sensitivity analyses (PSAs) were performed to test the robustness of the base-case scenario. The base-case scenario was changed to ACR20 criteria (scenario 1) and ACR70 criteria (scenario 2) to determine the model's robustness. Cost-effectiveness acceptability curves and cost-effectiveness frontiers were used to estimate the cost-effectiveness probability of each treatment strategy. A willingness-to-pay (WTP) threshold was defined as three times the US GDP per capita ($US139,143 per additional QALY gained). Primary results were presented as incremental cost-effective ratios (ICERs).Results: Etanercept+MTX was the most cost-effective treatment strategy in the base-case scenario up to a WTP threshold of $US2 185,497 per QALY gained. At a WTP threshold of greater than $US2 185,497 per QALY gained, certolizumab+MTX was the most cost-effective treatment strategy. One-way analyses showed that the base-case scenario was sensitive to the probability of achieving ACR50 criteria for MTX and each TNF-α inhibitor, and changes in the utility score for patients who achieved the ACR50 criteria. With the exception of infliximab, all of the TNF-α inhibitors were sensitive to drug cost per cycle. In the scenario analyses, certolizumab+MTX was a dominant treatment strategy using ACR20 criteria, but etanercept+MTX was a dominant treatment strategy using ACR70 criteria.Conclusions: Etanercept+MTX was a cost-effective treatment strategy in the base-case scenario; however, the model was sensitive to parameter uncertainties and ACR response criteria. Although Bayesian methods were used to determine transition probabilities, future studies will need to focus on head-to-head comparisons of multiple TNF-α inhibitors to provide valid comparisons. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the clinical and microbiological outcomes of linezolid versus vancomycin in methicillin-resistant Staphylococcus aureus (MRSA) complicated skin and soft-tissue infection (cSSTI) using a meta-analysis. RESEARCH DESIGN AND METHODS: Clinical trials were identified using PubMed, the Cochrane Central Register of Controlled Trials, and the International Pharmaceutical Abstracts from inception to March 2009. Primary outcomes evaluated resolution of signs and symptoms of infection in clinically evaluable (CE) patients, and microbiological eradication in both the modified intent-to-treat (MITT) and MRSA evaluable (MRSA ME) patients. MITT patients had a culture-confirmed Gram-positive pathogen (S. aureus) at baseline. Secondary outcomes included mortality, adverse drug reactions (ADR), and discontinuation due to ADRs. The Mantel-Haenszel odds ratios (OR) with 95% confidence intervals (CI) were calculated using the fixed effects model based on the assumption that there was little to no heterogeneity between the studies in the primary analysis. Sensitivity analyses were performed for each outcome by removing the most weighted study. RESULTS: Five studies with a total of 2652 patients (1361/linezolid; 1291/vancomycin) were identified. Resolution of infection in CE patients (OR = 1.41; 95% CI: 1.03, 1.95) and MITT patients (OR = 1.91; 95% CI: 1.33, 2.76) favored the use of linezolid over vancomycin, but did not remain significant after sensitivity analyses (CE: OR = 1.29; 95% CI: 0.81, 2.05; MITT: OR = 1.73; 95% CI: 0.87, 3.41). Microbiological eradication in MRSA ME patients consistently favored the use of linezolid over vancomycin (OR = 2.90; 95% CI: 1.90, 4.41). No difference in mortality was observed between the two groups (OR = 1.17; 95% CI: 0.85, 1.62). Higher proportions of linezolid patients were found to have diarrhea (119/1361 vs. 52/1291), nausea (102/1361 vs. 46/1291) and thrombocytopenia (54/1121 vs. 8/1071), whereas a higher proportion of vancomycin patients were found to have renal insufficiency compared to linezolid (16/634 vs. 4/703). Inconsistent results were seen with the incidence of anemia and rash between the base-case (anemia: OR = 1.36; 95% CI: 0.90, 2.08; rash: OR = 0.26; 95% CI: 0.10, 0.68) and sensitivity analyses (anemia: OR = 2.33; 95% CI: 1.24, 4.37; rash: OR = 0.57; 95% CI: 0.12, 2.71). Discontinuation due to ADRs was not statistically different between linezolid and vancomycin (OR = 1.06; 95% CI: 0.75, 1.51). CONCLUSION: Resolution of infection in CE and MITT patients were inconsistent; however, a sub-analysis revealed that linezolid was more likely to consistently achieve microbiologic eradication in MRSA ME patients. Apparent risks of thrombocytopenia, nausea, diarrhea, and possibly anemia may limit linezolid use in treating MRSA cSSTI. This study was limited due to an inability to assess for the effects of hetero-resistance and appropriate vancomycin dosing on outcomes. Moreover, the small number of studies made controlling for heterogeneity challenging. [ABSTRACT FROM AUTHOR]

Background: The primary aim compared kidney endpoints between patients with type 2 diabetes (T2D) 36 months after initiation on a sodium-glucose cotransporter-2 inhibitor (SGLT2i) or a GLP-1 receptor agonist (GLP-1RA). Secondary aims compared estimated glomerular filtration rate (eGFR), hemoglobin A1c (HbA1c), weight, and urine albumin-to-creatinine ratio (UACR) changes., Methods: We conducted a retrospective cohort study of propensity score matched veterans with T2D, baseline eGFR>20mL/min/1.73m2, and initiated on a SGLT2i vs GLP-1RA between 4/1/2009-9/1/2020. Cox proportional hazard models were constructed to evaluate effectiveness between both groups on composite endpoint (decline of >=40% in eGFR from baseline, ESRD event, and all-cause mortality) and its components adjusting for baseline characteristics. Spline models were constructed to evaluate eGFR change and linear mixed effects models were constructed to evaluate changes in HbA1c, weight, and UACR. We used an intent-to-treat (ITT) approach as our main analysis followed by a per-protocol (PP) approach excluding veterans who discontinued or switched therapy during the study period., Results: A total of 29,146 propensity score matched veterans were included in SGLT2i and GLP-1RA groups (14,573 per group). In the ITT and PP analyses, veterans initiated on SGLT2i had a 35% (HR=0.65; 95% CI: 0.62, 0.68) and 34% (HR=0.66; 95% CI: 0.62, 0.69) reduction in the hazard of experiencing the composite endpoint compared to veterans initiated on GLP-1RA adjusting for baseline characteristics, respectively. Between 6-36 months, we found an improved chronic eGFR slope with SGLT2i compared to GLP-1RA in both ITT and PP analyses; +1.19 mL/min/1.73 m2 (95% CI: 0.93, 1.45) and +1.29 mL/min/1.73m2 (95% CI: 1.01, 1.57), respectively. The annual difference in chronic eGFR slope in both ITT and PP analyses were +0.97 mL/min/1.73m2/year (95% CI: 0.82, 1.11) and +1.08 mL/min/1.73m2/year (95% CI: 0.92, 1.25). Improved HbA1c, weight loss and UACR were reported for both groups., Conclusion: In this real-world study, veterans with T2D initiated on SGLT2i were associated with reduced hazard of experiencing mortality, worsening eGFR, or developing ESRD and improved glycemic, metabolic, and renal endpoints compared to GLP-1RA use., (Copyright © 2024 Written work prepared by employees of the Federal Government as part of their official duties is, under the U.S. Copyright Act, a “work of the United States Government” for which copyright protection under Title 17 of the United States Code is not available. As such, copyright does not extend to the contributions of employees of the Federal Government.)