Cost-effectiveness of treating relapsed or refractory 3L+ follicular lymphoma with axicabtagene ciloleucel vs mosunetuzumab in the United States.

Introduction: Novel therapies for 3L+ relapsed/refractory (r/r) follicular lymphoma (FL) have been approved recently by the US Food and Drug Administration including anti-CD19 CAR-T therapies such as axicabtagene ciloleucel (axi-cel) and CD20 × CD3 T-cell-engaging bispecific monoclonal antibodies such as mosunetuzumab (mosun). The objective of this study was to assess the cost-effectiveness of axi-cel compared to mosun in 3L+ r/r FL patients from a US third-party payer perspective. Methods: A three-state (progression-free, progressed disease, and death) partitioned-survival model was used to compare two treatments over a lifetime horizon in a hypothetical cohort of US adults (age ≥18) receiving 3L+ treatment for r/r FL. ZUMA-5 and GO29781 trial data were used to inform progression-free survival (PFS) and overall survival (OS). Mosun survival was modeled via hazard ratios (HRs) applied to axi-cel survival curves. The PFS HR value was estimated via a matching-adjusted indirect comparison (MAIC) based on mosun pseudo-individual patient data and adjusted axi-cel data to account for trial populations differences. One-way sensitivity analysis (OWSA) and probabilistic sensitivity analyses (PSA) were conducted. Scenario analyses included: 1) the mosun HRs were applied to the weighted (adjusted) ZUMA-5 24-month data to most exactly reflect the MAIC, 2) mosun HR values were applied to axi-cel 48-month follow-up data, and 3) recent axi-cel health state utility values in diffuse large B-cell lymphoma patients. Results: The analysis estimated increases of 1.82 LY and 1.89 QALY for axi-cel compared to mosun. PFS for axi-cel patients was 6.42 LY vs. 1.60 LY for mosun. Increase of $257,113 in the progression-free state was driven by one-time axi-cel treatment costs. Total incremental costs for axi-cel were $204,377, resulting in an ICER of $108,307/QALY gained. The OWSA led to ICERs ranging from $240,255 to $75,624, with all but two parameters falling below $150,000/QALY. In the PSA, axi-cel had an 64% probability of being cost-effective across 5,000 iterations using a $150,000 willingness-to-pay threshold. Scenarios one and two resulted in ICERs of $105,353 and $102,695, respectively. Discussion: This study finds that axi-cel is cost-effective compared to mosun at the commonly cited $150,000/QALY US willingness-to-pay threshold, with robust results across a range of sensitivity analyses accounting for parameter uncertainty.

Epidemiology and outcomes of residual neuromuscular blockade: A systematic review of observational studies.

OBJECTIVES: Complete reversal of neuromuscular blockade (NMB) is important for patient safety and prognosis following surgical procedures involving NMB agents (NMBAs). Published evidence on the epidemiology and consequences of residual neuromuscular blockade (rNMB; incomplete neuromuscular recovery) in real-world clinical settings is lacking with advances in NMB management. Therefore, we aimed to examine the burden of rNMB and its associated clinical, economic and humanistic outcomes using a systematic review framework. REVIEW METHODS: Electronic and conference database searches were performed to include observational studies examining rNMB or related outcomes in adults undergoing surgery and receiving NMBAs with or without NMBA antagonists. RESULTS: Of 1438 screened abstracts, 58 studies with 25,277 total patients were included. Inconsistent definitions of rNMB were reported across studies with 44 (76%) and 29 (50%) studies utilizing quantitative and qualitative measures to detect rNMB, respectively. The most common definition of rNMB was train-of-four ratio (TOFR) <0.9 (29 studies) and TOFR <0.7 (16 studies) measured at post-anesthesia care unit (PACU) entry. For TOFR <0.9 at PACU entry, rNMB incidence ranged from 0% to 90.5% (median 30%) overall; 0% to 16.0% in the sugammadex (SUG) group; 3.5% to 90.5% in the neostigmine (NEO) group; and 15% to 89% in the spontaneous recovery (SR) group. Twenty-one studies reported clinical outcomes (reintubation, mild hypoxemia, or a respiratory event) or resource utilization outcomes (hospital/PACU length of stay [LOS]) by presence/absence of rNMB. Patients with rNMB had higher rates of acute respiratory events compared to those without rNMB. CONCLUSIONS: Real-world observational studies show a significant burden of rNMB and associated health sequelae, though rNMB measures were not reported consistently across studies. Appropriate quantitative measurement is needed to accurately identify rNMB, and interventions are needed to reduce its burden and associated adverse outcomes.

Budget impact analysis of sarilumab for the treatment of rheumatoid arthritis in patients with an inadequate response to conventional synthetic DMARD or TNF inhibitor therapies.

OBJECTIVE: To estimate the 5-year budget impact (BI) on a US health plan of introducing sarilumab - a human immunoglobulin G1 anti-IL-6 receptor α monoclonal antibody - as combination treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or monotherapy in patients with moderate-to-severe rheumatoid arthritis (RA). METHODS: BI analysis was conducted from a commercial payer perspective. Treatment-eligible populations included adult patients with moderate-to-severe RA and inadequate response (IR) to csDMARDs or tumor necrosis factor (TNF)-α inhibitors-IR. All licensed biologic treatments recommended by the American College of Rheumatology guidelines were included. RESULTS: For a hypothetical plan of one million members, 409 csDMARD-IR and 345 TNF-IR patients were annually eligible for combination therapy and 226 csDMARD and TNF-IR patients for monotherapy with sarilumab. Based on 2018 US direct treatment costs, the introduction of sarilumab was estimated to save $526,424, $322,637 and $264,306 over 5 years for csDMARD-IR combination therapy patients, TNF-IR combination therapy patients, and csDMARD-IR/TNF-IR monotherapy patients, respectively. As sarilumab absorbed a greater market share over the horizon, annual savings increased from years 1 to 5, $28,610 (-0.14%) to $194,646 (-0.83%) in csDMARD-IR, $16,986 (-0.11%) to $120,893 (-0.67%) in TNF-IR, and $14,256 (-0.13%) to $98,040 (-0.79%) in monotherapy. One-way sensitivity analyses revealed that the model was most sensitive to variations in sarilumab adherence. CONCLUSION: Total cost savings of introducing sarilumab to a health-care plan accrued from years 1 to 5, attributable to the lower treatment cost, stable dosing paradigm, and price parity for the two available doses (150 and 200 mg every 2 weeks) compared with alternative biologic DMARDs that have substantial variability in dose titration/schedules.

A cost-benefit analysis of smoking cessation prescription coverage from a US payer perspective.

INTRODUCTION: Smoking drives substantial direct health care spending, comprising 8.7% ($168 billion) of annual United States aggregated spending. Smoking cessation (SC) prescription use is an effective strategy to improve health outcomes, increase quit rates, and reduce economic burden. However, patient out-of-pocket costs may limit the use. Health care payers play a vital role in driving use through formulary decisions and copayment policies but must consider both the near-term financial investment as well as downstream effects of increased coverage on health care budgets. This study estimates the return on investment (ROI) of providing Affordable Care Act (ACA)-recommended prescription SC coverage. METHODS: A cost-benefit analysis (CBA) estimates the ROI of providing prescription SC coverage, based on pharmacy costs and savings from smoking-attributable medical expenditures among Medicare, Medicaid, and commercial plan enrollees over 10 years. The CBA incorporated national-level population demographics, smoking prevalence estimates, proportion of smokers attempting to quit, and the utilization of SC products. A five-state Markov chain model simulated patterns of quit attempts, relapse, and cessation assuming two quit attempts per year, no patient cost-sharing, and 25.4% utilization of prescription SC aids. Results include number of quitters, annual pharmacy and smoking-attributable medical costs, and ROI. RESULTS: After initial investment in SC treatment, smoking-attributable medical benefits accrue over time, generating a positive ROI by year 4 for commercial (11.3%) and Medicaid (78.4%) plans and by year 3 for Medicare (30.6%). Over 10 years, an average return of $1.18, $2.50, and $3.22 savings per dollar spent on SC prescriptions for commercial, Medicaid, and Medicare plans, respectively, may be realized. DISCUSSION: Given the proven efficacy of SC pharmacotherapy, near-term investments in supporting ACA-recommended SC coverage translate into a positive ROI. As smoking is a leading cause of morbidity and mortality, increased access to prescription SC medications may improve health outcomes and reduce smoking-attributable costs to payers over time.

Estimated Budget Impact of Adopting the Affordable Care Act's Required Smoking Cessation Coverage on United States Healthcare Payers.

INTRODUCTION: Despite abundant information on the negative impacts of smoking, more than 40 million adult Americans continue to smoke. The Affordable Care Act (ACA) requires tobacco cessation as a preventive service with no patient cost share for all FDA-approved cessation medications. Health plans have a vital role in supporting smoking cessation by managing medication access, but uncertainty remains on the gaps between smoking cessation requirements and what is actually occurring in practice. This study presents current cessation patterns, real-world drug costs and plan benefit design data, and estimates the 1- to 5-year pharmacy budget impact of providing ACA-required coverage for smoking cessation products to understand the fiscal impact to a US healthcare plan. METHODS: A closed cohort budget impact model was developed in Microsoft Excel® to estimate current and projected costs for US payers (commercial, Medicare, Medicaid) covering smoking cessation medicines, with assumptions for coverage and smoking cessation product utilization based on current, real-world national and state-level trends for hypothetical commercial, Medicare, and Medicaid plans with 1 million covered lives. A Markov methodology with five health states captures quit attempt and relapse patterns. Results include the number of smokers attempting to quit, number of successful quitters, annual costs, and cost per-member per-month (PMPM). RESULTS: The projected PMPM cost of providing coverage for smoking cessation medications is $0.10 for commercial, $0.06 for Medicare, and $0.07 for Medicaid plans, reflecting a low incremental PMPM impact of covering two attempts ranging from $0.01 for Medicaid to $0.02 for commercial and Medicare payers. CONCLUSION: The projected PMPM impact of covering two quit attempts with access to all seven cessation medications at no patient cost share remains low. Results of this study reinforce that the impact of adopting the ACA requirements for smoking cessation coverage will have a limited near-term impact on health plan's budgets. FUNDING: Pfizer Inc.

Safety assessment of an anti-obesity drug (sibutramine): a retrospective cohort study.

BACKGROUND: Obesity is a serious and rapidly growing health problem worldwide. Few therapies are available beyond diet, exercise and bariatric surgery. A previously approved medication, sibutramine, has been withdrawn from the market due to concerns over the potential of increased risk of cardiovascular (CV) events, based on a phase IV clinical trial that included only individuals at high risk for CV events. OBJECTIVE: The aim of the study was to compare sibutramine users and matched non-users on rates of CV events, both overall and stratified by whether the patient qualified for on-label sibutramine use, using data from real-life clinical practice. METHODS: A retrospective cohort was constructed from electronic medical record data from physician office practices (mostly primary care) in the UK and Germany, using the LifeLink™ database from IMS Health Incorporated. For patients with at least one physician visit in which sibutramine was prescribed between 1 April 1999 and 31 October 2008, the date of their first such prescription was their index date. Users and non-users were matched 1 : 1 on index date (within 30 days), sex, age group (six categories), Charlson Comorbidity Index and evidence of obesity (high body mass index [BMI] or, if BMI was missing, diagnosis of obesity or very high weight relative to height). The resultant total samples analysed were 6186 in Germany and 7264 in the UK. User and non-user cohorts in the samples were compared according to the ratio of their crude incidence rates of acute myocardial infarction (AMI), stroke and either AMI or stroke per 1000 patient-years of follow-up. Cox regression analysis was used to compare the risk of CV events as a hazard ratio (HR) with 95% confidence intervals (CIs) between sibutramine user and non-user cohorts, controlling for label status and/or history of prior CV disease at baseline. RESULTS: The risk of AMI, stroke and either AMI or stroke was not higher among sibutramine users than comparable non-users of sibutramine in both Germany and the UK [Germany: HR 0.47 (95% CI 0.17, 1.26), 0.43 (0.23, 0.81) and 0.44 (0.26, 0.75), respectively; UK: HR 0.44 (0.15, 1.31), 0.63 (0.25, 1.60) and 0.54 (0.27, 1.10), respectively]. Regardless of whether or not the model controlled for prior CV disease (CVD), the direction and statistical significance of the differences did not change. In the sensitivity analyses including only those without a history of CVD in the 365 days prior to the index date there was no increased risk of CV events in either Germany or the UK. CONCLUSION: This study offers a framework for the safety assessment of anti-obesity drugs using an observational epidemiological study design. Large electronic health databases were used to construct retrospective cohorts to examine the risk in a population using one specific anti-obesity drug. Use of sibutramine in general practice settings was not found to increase the risk of acute CV events.