Modelling the potential long-term survival benefit of evinacumab treatment vs. standard of care in patients with homozygous familial hypercholesterolaemia.

AIMS: Despite intensive lipid-lowering therapies (LLTs), most patients with homozygous familial hypercholesterolaemia (HoFH) do not achieve guideline recommended low-density lipoprotein cholesterol (LDL-C) targets and are at increased risk of premature cardiovascular death. This analysis aimed to predict the impact of evinacumab and standard-of-care LLTs on life expectancy in an HoFH population using mathematical modelling. METHODS AND RESULTS: Mathematical models were developed using efficacy data for evinacumab from the phase 3 ELIPSE HoFH trial plus efficacy data for standard-of-care LLTs from peer-reviewed publications. Treatment strategies evaluated included (i) untreated, (ii) high-intensity statin (HIS) only, (iii) HIS plus ezetimibe, (iv) HIS plus ezetimibe plus proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i), and (v) HIS plus ezetimibe plus PCSK9i plus evinacumab. Markov analyses were used to assess differences in survival probability for different LLT strategies. The median survival for untreated HoFH patients was only 33-43 years, depending on different assumptions on baseline untreated LDL-C levels. In the most robust model, we estimated that HIS increased median survival by 9 years and ezetimibe further increased median survival by an additional 9 years. When PCSK9i was added on top of HIS plus ezetimibe, median survival was further improved by 14 years. Finally, the addition of evinacumab to standard-of-care LLTs was estimated to increase median survival by ∼12 years. CONCLUSION: In this mathematical modelling analysis, evinacumab treatment could potentially increase long-term survival vs. standard-of-care LLTs for patients with HoFH.

This mathematical modelling analysis demonstrated that evinacumab in addition to standard-of-care lipid-lowering treatments (LLTs; high-intensity statin plus ezetimibe plus proprotein convertase subtilisin/kexin type 9 inhibitor) could increase long-term survival to a median of 77 years vs. the 65 years achieved with only standard-of-care LLTs in patients with homozygous familial hypercholesterolaemia.

Assessing the Combined Public Health Impact of Pharmaceutical Interventions on Pandemic Transmission and Mortality: An Example in SARS CoV-2.

To assess the combined role of anti-viral monoclonal antibodies (mAbs) and vaccines in reducing severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) transmission and mortality in the United States, an agent-based model was developed that accounted for social contacts, movement/travel, disease progression, and viral shedding. The model was calibrated to coronavirus disease 2019 (COVID-19) mortality between October 2020 and April 2021 (aggressive pandemic phase), and projected an extended outlook to estimate mortality during a less aggressive phase (April-August 2021). Simulated scenarios evaluated mAbs for averting infections and deaths in addition to vaccines and aggregated non-pharmaceutical interventions. Scenarios included mAbs as a treatment of COVID-19 and for passive immunity for postexposure prophylaxis (PEP) during a period when variants were susceptible to the mAbs. Rapid diagnostic testing paired with mAbs was evaluated as an early treatment-as-prevention strategy. Sensitivity analyses included increasing mAb supply and vaccine rollout. Allocation of mAbs for use only as PEP averted up to 14% more infections than vaccine alone, and targeting individuals ≥ 65 years averted up to 37% more deaths. Rapid testing for earlier diagnosis and mAb use amplified these benefits. Doubling the mAb supply further reduced infections and mortality. mAbs provided benefits even as proportion of the immunized population increased. Model projections estimated that ~ 42% of expected deaths between April and August 2021 could be averted. Assuming sensitivity to mAbs, their use as early treatment and PEP in addition to vaccines would substantially reduce SARS-CoV-2 transmission and mortality even as vaccination increases and mortality decreases. These results provide a template for informing public health policy for future pandemic preparedness.

Network meta-analysis of immune-oncology monotherapy as first-line treatment for advanced non-small-cell lung cancer in patients with PD-L1 expression ⩾50.

Background: For patients with advanced non-small-cell lung cancer (NSCLC) and high (⩾50%) programmed cell death-ligand 1 (PD-L1) expression, effective first-line immune-oncology monotherapies with significant survival benefits are approved, cemiplimab being the most recent. In a phase III trial, cemiplimab demonstrated significantly improved overall survival (OS) and progression-free survival (PFS) versus chemotherapy in patients with advanced NSCLC and PD-L1 ⩾50%. A systematic literature review and network meta-analysis (NMA) was conducted to identify/compare the efficacy/safety of cemiplimab versus pembrolizumab or other immune-oncology monotherapies from randomized-controlled trials (RCTs) published in November 2010-2020. Methods: Relevant RCTs were identified by searching databases and conference proceedings as per ISPOR, NICE, and Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. NMA with time-varying hazard ratios (HRs) was performed for OS and PFS. Analyses were conducted for objective response rate (ORR) and safety/tolerability. Fixed-effect models were used due to limited evidence. Various sensitivity analyses were conducted to validate the base case analyses. Results: The feasibility assessment determined that EMPOWER-Lung 1, KEYNOTE-024, and KEYNOTE-042 trials were eligible. IMpower110 was excluded because an incompatible PD-L1 assay (SP142) was used for patient selection. For first-line advanced NSCLC with PD-L1 ⩾50%, cemiplimab was associated with statistically significant improvements in PFS [HR (95% credible interval [CrI]): 0.65 (0.50-0.86), 1-12 months] and ORR [odds ratio (OR) (95% CrI): 1.64 (1.04-2.62)], and comparable OS [HR (95% CrI): 0.77 (0.54-1.10), 1-12 months] versus pembrolizumab. There was no evidence of differences between cemiplimab and pembrolizumab for Grade 3-5 adverse events (AEs) [OR (95% CrI): 1.47 (0.83-2.60)], immune-mediated AEs [1.75 (0.33-7.49)], and all-cause discontinuation due to AEs [1.21 (0.58-2.61)]. Conclusions: Considering the limitations of indirect treatment comparisons, in patients with advanced NSCLC and PD-L1 ⩾50%, cemiplimab monotherapy demonstrated significant improvements in PFS and ORR, comparable OS, and no evidence of differences in safety/tolerability versus pembrolizumab.

Cost-effectiveness of casirivimab/imdevimab in patients with COVID-19 in the ambulatory setting.

BACKGROUND: Most patients infected with SARS-CoV-2, resulting in COVID-19, have only mild symptoms that can be managed in an ambulatory setting. However, a significant number of patients develop a more severe form of the disease and require hospital care, with the risk of long-term sequelae or death. Casirivimab/imdevimab is a combination of 2 recombinant human monoclonal antibodies that has been shown to significantly reduce the risk of hospitalization or death in patients with mild to moderate COVID-19 in the ambulatory setting. OBJECTIVE: To establish the cost-effectiveness of casirivimab/imdevimab in ambulatory individuals with COVID-19. METHODS: A cost-effectiveness model was constructed to simulate the natural history of COVID-19 in ambulatory patients and to identify those patients for whom casirivimab/imdevimab may be a cost-effective treatment from a US payer perspective. Patients enter the model in the ambulatory health state and can receive either active treatment with casirivimab/imdevimab or usual care. Patients can either recover from the infection or be hospitalized, from where they can recover from infection or die. Following this acute phase, patients enter a Markov model to estimate lifetime quality-adjusted life years. The model uses the risk of hospitalization in both the active treatment and usual care cohorts, and age- and sex-specific risk of mortality. Other model inputs include hospitalization costs and health-related utilities in the ambulatory acute treatment phase, the hospitalized setting, and the post-acute phase. Accounting for the heterogeneity of risk by age and comorbidities, results are presented separately for various combinations of baseline age and usual care risk in a 7 × 9 matrix. Outcomes related to "long COVID" are assessed in scenario analyses. RESULTS: In the base case, at a willingness-to-pay threshold of $100,000, treatment with casirivimab/imdevimab was found to be cost-effective in most patients, including those older than 40 years of age with a baseline hospitalization risk greater than or equal to 2% and patients aged 20 years with a baseline risk of hospitalization greater than or equal to 4%, whereas for hospitalization risk greater than or equal to 10%, casirivimab/imdevimab is dominant. Casirivimab/imdevimab was not cost-effective in patients aged 20 years with a 3% or lower risk of hospitalization or in patients aged 30 years with a 2% risk. CONCLUSIONS: This economic analysis found that casirivimab/imdevimab is a cost-effective treatment for most ambulatory patients with COVID-19. DISCLOSURES: N. Jovanoski and U. Becker are employees of F Hoffman-La Roche Ltd.; A. Kuznik and M. Hussein are employees of Regeneron Pharmaceuticals Inc. and hold stock and stock options; A. Briggs has provided consultancy to F Hoffman-La Roche Ltd. and has received consultancy fees from Merck and Co., Inc., GlaxoSmithKline plc., and Novartis. This study was funded by Regeneron Pharmaceuticals, Inc.

Cost-Effectiveness of Cemiplimab Versus Standard of Care in the United States for First-Line Treatment of Advanced Non-small Cell Lung Cancer With Programmed Death-Ligand 1 Expression ≥50.

OBJECTIVES: This study aimed to evaluate the cost-effectiveness, from a US commercial payer perspective, of cemiplimab versus other first-line treatments for advanced non-small cell lung cancer with programmed death-ligand 1 expression ≥50%. METHODS: A 30-year "partitioned survival" model was constructed. Overall survival and progression-free survival were estimated by applying time-varying hazard ratios from a network meta-analysis of randomized clinical trials. Overall survival and progression-free survival were estimated from EMPOWER-Lung 1 (cemiplimab monotherapy vs chemotherapy) and KEYNOTE-024 and KEYNOTE-042 (pembrolizumab monotherapy vs chemotherapy). Drug acquisition costs were based on published 2020 US list prices. A 3% discount rate was applied to life-years, quality-adjusted life-years (QALYs), and costs. A deterministic analysis was performed on the base case; 1-way sensitivity and probabilistic sensitivity analyses assessed model and parameter uncertainties. RESULTS: Cemiplimab was associated with increased time in the "preprogression" (13.08 vs 7.90 and 6.08 months) and "postprogression" (47.30 vs 29.49 and 14.78 months) health states versus pembrolizumab and chemotherapy, respectively. Compared with pembrolizumab and chemotherapy, cemiplimab generated 1.00 (95% CI -0.266 to 2.440) and 1.78 (95% CI 0.607-3.20) incremental QALYs, respectively, with incremental cost-effectiveness ratios of $68 254 and $89 219 per QALY for cemiplimab versus pembrolizumab and cemiplimab versus chemotherapy, respectively. The probability of cemiplimab being cost-effective at a willingness-to-pay threshold of $100 000 to $150 000 per QALY was 62% to 76% versus pembrolizumab and 56% to 84% versus chemotherapy. CONCLUSIONS: Findings suggest that cemiplimab, versus pembrolizumab or versus chemotherapy, is a cost-effective first-line treatment option for advanced non-small cell lung cancer with programmed death-ligand 1 expression ≥50%.

Impact of the treatment crossover design on comparative efficacy in EMPOWER-Lung 1: Cemiplimab monotherapy as first-line treatment of advanced non-small cell lung cancer.

Objectives: In randomized-controlled crossover design trials, overall survival (OS) treatment effect estimates are often confounded by the control group benefiting from treatment received post-progression. We estimated the adjusted OS treatment effect in EMPOWER-Lung 1 (NCT03088540) by accounting for the potential impact of crossover to cemiplimab among controls and continued cemiplimab treatment post-progression. Methods: Patients were randomly assigned 1:1 to cemiplimab 350 mg every 3 weeks (Q3W) or platinum-doublet chemotherapy. Patients with disease progression while on or after chemotherapy could receive cemiplimab 350 mg Q3W for ≤108 weeks. Those who experienced progression on cemiplimab could continue cemiplimab at 350 mg Q3W for ≤108 additional weeks with four chemotherapy cycles added. Three adjustment methods accounted for crossover and/or continued treatment: simplified two-stage correction (with or without recensoring), inverse probability of censoring weighting (IPCW), and rank-preserving structural failure time model (RPSFT; with or without recensoring). Results: In the programmed cell death-ligand 1 ≥50% population (N=563; median 10.8-month follow-up), 38.2% (n=107/280) crossed over from chemotherapy to cemiplimab (71.3%, n=107/150, among those with confirmed progression) and 16.3% (n=46/283) received cemiplimab treatment after progression with the addition of histology-specific chemotherapy (38.7%, n=46/119, among those with confirmed progression). The unadjusted OS hazard ratio (HR) with cemiplimab versus chemotherapy was 0.566 (95% confidence interval [CI]: 0.418, 0.767). Simplified two-stage correction-the most suitable method based on published guidelines and trial characteristics-produced an OS HR of 0.490 (95% CI: 0.365, 0.654) without recensoring and 0.493 (95% CI: 0.361, 0.674) with recensoring. The IPCW and RPSFT methods produced estimates generally consistent with simplified two-stage correction. Conclusions: After adjusting for treatment crossover and continued cemiplimab treatment after progression with the addition of histology-specific chemotherapy observed in EMPOWER-Lung 1, cemiplimab continued to demonstrate a clinically important and statistically significant OS benefit versus chemotherapy, consistent with the primary analysis.

Cost-effectiveness analysis of cemiplimab vs pembrolizumab for treatment of advanced cutaneous squamous cell carcinoma.

BACKGROUND: Most cutaneous squamous cell carcinomas (CSCCs) can be treated with surgical excision or radiation; however, approximately 1% of patients develop advanced disease. In 2018, the FDA approved cemiplimab-rwlc as the first programmed cell death-1 (PD-1) monoclonal antibody for the treatment of patients with metastatic CSCC or locally advanced CSCC who are not candidates for curative surgery or curative radiation. In June 2020, pembrolizumab, another PD-1 monoclonal antibody, was approved for the treatment of patients with recurrent or metastatic CSCC who are not candidates for curative surgery or radiation. We previously reported on the cost-effectiveness of cemiplimab vs historical standard of care for the treatment of advanced CSCC from a US perspective. OBJECTIVE: To estimate the cost-effectiveness of cemiplimab vs pembrolizumab for patients with advanced CSCC in the United States. METHODS: A "partitioned survival" framework was used to assess the cost-effectiveness of cemiplimab vs pembrolizumab. Clinical inputs were based on the most recent data cut of the phase 2 trials for cemiplimab (EMPOWER-CSCC-1; NCT02760498) and pembrolizumab (KEYNOTE-629). Progression-free survival and overall survival were extrapolated using parametric models until all patients had progressed or died. Health state utilities were derived from data collected in the EMPOWER-CSCC-1 trial. Costs included drug acquisition, drug administration, disease management, terminal care, and adverse events and were based on published 2020 US list prices. To assess model uncertainty, 1-way sensitivity and probabilistic sensitivity analyses (PSA) were conducted, alongside scenario analyses evaluating key modeling assumptions. RESULTS: In the base case, cemiplimab resulted in an incremental gain of 3.44 life-years (discounted) and incremental cost-effectiveness ratio (ICER) of $130,329 per quality-adjusted life-year (QALY) vs pembrolizumab. At a willingness-to-pay threshold of $150,000/QALY, PSA indicated a 71% probability that cemiplimab is cost-effective when compared with pembrolizumab. Scenario analysis resulted in ICERs ranging from $115,909 to $187,374. CONCLUSIONS: Findings suggest that cemiplimab is a cost-effective treatment for patients with advanced CSCC, compared with pembrolizumab. These results should be interpreted cautiously in the absence of head-to-head trials; however, in the absence of such data, these results can be used to inform health care decisions over resource allocation. DISCLOSURES: This study was supported by Regeneron Pharmaceuticals, Inc., and Sanofi. Paul, Cope, Keeping, Mojebi, and Ayers are employees of PRECISIONheor, which received funding to produce this work. Chen, Kuznik, and Xu are employees and stockholders of Regeneron Pharmaceuticals, Inc. Sasane is an employee and stockholder of Sanofi, Inc. Konidaris, Atsou, and Guyot are employees of Sanofi, Inc. The authors were responsible for all content and editorial decisions and received no honoraria related to the development of this publication.

Assessing the Value of Cemiplimab for Adults With Advanced Cutaneous Squamous Cell Carcinoma: A Cost-Effectiveness Analysis.

OBJECTIVES: To evaluate the cost-effectiveness of cemiplimab in patients with advanced cutaneous squamous cell carcinoma (CSCC) from a payer perspective in the United States. METHODS: A partitioned survival model was developed to assess the cost-effectiveness of cemiplimab versus historical standard of care (SOC). All inputs were identified based on a systematic literature review, supplemented by expert opinion where necessary. Clinical inputs for cemiplimab were based on individual patient data from a cemiplimab phase 2 single-arm trial (NCT27060498). For SOC, analysis was based on a pooled analysis of single-arm clinical trials and retrospective studies evaluating chemotherapy and epidermal growth factor receptor inhibitors (cetuximab, erlotinib, and gefitinib) identified via a systematic literature review (6 of the 27 included studies). Overall survival and progression-free survival were extrapolated over a lifetime horizon. Costs were included for drug acquisition, drug administration, management of adverse events, subsequent therapy, disease management, and terminal care. Unit costs were based on published 2019 US list prices. RESULTS: In the base case, cemiplimab versus SOC resulted in an incremental cost-effectiveness ratio of $99 447 per quality adjusted-life year (QALY), where incremental costs and QALYs were $372 108 and 3.74, respectively. At a willingness-to-pay threshold of $150 000/QALY, the probabilistic sensitivity analysis suggests a 90% probability that cemiplimab is cost-effective compared to SOC. Scenario analyses resulted in incremental cost-effectiveness ratios ranging from $90 590 to $148 738. CONCLUSIONS: Compared with historical SOC, cemiplimab is a cost-effective use of US payer resources for the treatment of advanced CSCC and is expected to provide value for money.

Comparative efficacy of cemiplimab versus other systemic treatments for advanced cutaneous squamous cell carcinoma.

Aim: To estimate the comparative efficacy of cemiplimab, a programmed cell death protein 1 inhibitor, versus EGFR inhibitors, pembrolizumab and platinum-based chemotherapy in terms of overall survival (OS) and progression-free survival. Patients & methods: We performed an indirect treatment comparison of cemiplimab and other available systemic therapies for patients with advanced cutaneous squamous cell carcinoma. Results: Cemiplimab was associated with benefits in OS (hazard ratios range: 0.07-0.52) and progression-free survival (hazard ratios range: 0.30-0.67) versus EGFR inhibitors and pembrolizumab (data from KEYNOTE-629). Cemiplimab was more efficacious versus platinum-based chemotherapy in terms of OS. Conclusion: Cemiplimab may offer improvements in survival for advanced cutaneous squamous cell carcinoma patients compared with existing systemic therapies.

Real-world persistence with dupilumab among adults with atopic dermatitis.

BACKGROUND: The real-world persistence with dupilumab therapy for atopic dermatitis (AD) is unknown. OBJECTIVE: To characterize adults with AD who initiated dupilumab and evaluate persistence with dupilumab therapy. METHODS: This retrospective cohort study used the IBM MarketScan Commercial and Medicare database. Adults with AD who initiated dupilumab (first dispensation = index date) between March 28, 2017, and March 31, 2018, were identified and followed up until September 30, 2018, or disenrollment. Twelve months of continuous preindex enrollment were required to characterize baseline treatment history and comorbidities. Kaplan-Meier analysis was used to estimate dupilumab persistence at 6 and 12 months, assuming a 14-day injection frequency and a 30-day grace period. RESULTS: A total of 1963 adults were identified who initiated dupilumab (mean [SD] age 42.1 [15.7] years; 50.7% women; 49.8% with ≥1 atopic comorbidity). Baseline AD treatments included topical corticosteroids (81.6%), systemic corticosteroids (72.5%), and systemic immunosuppressants (22.8%). Dupilumab persistence (95% confidence interval) at 6 and 12 months was 91.9% (90.7%-93.2%) and 77.3% (75.0%-79.7%), respectively. Among 329 patients who discontinued dupilumab, the risk of reinitiation was 78.8% (95% confidence interval: 75.8%-81.7%) within an average of 4 months. CONCLUSION: Dupilumab persistence at 12 months was high, suggesting patient satisfaction with effectiveness, tolerability, and treatment regimen.

Incremental Costs Associated with Length of Hospitalization Due to Viral Pneumonia: Impact of Intensive Care and Economic Implications of Reducing the Length of Stay in the Era of COVID-19.

BACKGROUND: Emerging trial data for treatment of COVID-19 suggest that in addition to improved clinical outcomes, these treatments reduce length of hospital stay (LOS). However, the economic value of a shortened LOS is unclear. OBJECTIVE: To estimate incremental costs per day of hospitalization for a patient with influenza or viral pneumonia, as a proxy for COVID-19; ICU costs associated with invasive mechanical ventilation (iMV) were also determined. METHODS: Retrospective analysis of claims-based data was conducted using the IBM MarketScan® Commercial Claims and Encounters and Medicare Supplemental and Coordination of Care and the Medicare Fee-for-Service claims databases for hospitalizations due to influenza/viral pneumonia between January 2018 and June 2019. Cases were stratified as uncomplicated hospitalizations or with ICU. Ordinary least squares regression, excluding LOS or costs exceeding the 99th percentile (base case), was used to estimate incremental costs per day; a sensitivity analysis included all qualified hospitalizations. Additional sensitivity analyses used weighting methodology. RESULTS: Among 6055 and 118,419 hospitalizations in the commercially insured and Medicare databases, respectively, 5958 and 116,552 hospitalizations, respectively, represented the base case. Estimated incremental base case costs per additional inpatient day were $2158 and $3900 in the commercial population for uncomplicated hospitalizations and hospitalizations with ICU, respectively, and $475 and $668, respectively in the Medicare population. Estimated incremental base case costs per additional ICU day were $5254 and $608 for Commercial and Medicare populations, respectively. Higher absolute costs were estimated in the sensitivity analysis on all qualified hospitalizations; the weighted sensitivity analyses generally showed that estimates were stable. Use of iMV increased costs by $35,482 and $13,101 in the commercial and Medicare populations, respectively. CONCLUSION: The incremental daily cost of a hospitalization is substantial for US patients with commercial insurance and for Medicare patients. These findings may help quantify the economic value of COVID-19 treatments that reduce LOS.

Costs and Cost Drivers of Providing Option B+ Services to Mother-Baby Pairs for PMTCT of HIV in Health Centre IV Facilities in Jinja District, Uganda.

BACKGROUND: In 2013, the World Health Organization (WHO) revised the 2012 guidelines on use of antiretroviral drugs (ARVs) for the prevention of mother-to-child transmission (PMTCT) of human immunodeficiency virus (HIV). The new guidelines recommended lifelong antiretroviral therapy (ART) for all HIV-positive pregnant and breastfeeding women irrespective of CD4 count or clinical stage (also referred to as Option B+). Uganda started implementing Option B+ in 2012 basing on the 2012 WHO guidelines. Despite the impressive benefits of the Option B+ strategy, implementation challenges, including cost burden and mother-baby pairs lost to follow-up, threatened its overall effectiveness. The researchers were unable to identify any studies conducted to assess costs and cost drivers associated with provision of Option B+ services to mother-baby pairs in HIV care in Uganda. Therefore, this study determined costs and cost drivers of providing Option B+ services to mother-baby pairs over a two-year period (2014-2015) in selected health facilities in Jinja district, Uganda. METHODS: The estimated costs of providing Option B+ to mother-baby pairs derived from the provider perspective were evaluated at four health centres (HC) in Jinja district. A retrospective, ingredient-based costing approach was used to collect data for 2014 as base year using a standardized cost data capture tool. All costs were valued in United States dollars (USD) using the 2014 midyear exchange rate. Costs incurred in the second year (2015) were obtained by inflating the 2014 costs by the ratio of 2015 and 2014 USA Gross Domestic Product (GDP) implicit price deflator. RESULTS: The average total cost of Option B+ services per HC was 66,512.7 (range: 32,168.2-102,831.1) USD over the 2-year period. The average unit cost of Option B+ services per mother-baby pair was USD 441.9 (range: 422.5-502.6). ART for mothers was the biggest driver of total mean costs (percent contribution: 62.6%; range: 56.0%-65.5%) followed by facility personnel (percent contribution: 8.2%; range: 7.7%-11.6%), and facility-level monitoring and quality improvement (percent contribution: 6.0%; range: 3.2%-12.3%). Conclusions and Recommendations. ART for mothers was the major cost driver. Efforts to lower the cost of ART for PMTCT would make delivery of Option B+ affordable and sustainable.

Social Cost of Blindness Due to AMD and Diabetic Retinopathy in the United States in 2020.

BACKGROUND AND OBJECTIVE: To estimate the social cost of blindness due to wet age-related macular degeneration (wAMD), diabetic macular edema (DME), and proliferative diabetic retinopathy (PDR) in the United States in 2020. PATIENTS AND METHODS: Excess costs that occur because of blindness were estimated as the difference in costs in blind versus non-blind individuals. Per-patient costs were aggregated using the number of cases of blindness due to wAMD, DME, and PDR projected in 2020. RESULTS: Associated annual excess direct costs, indirect costs, and quality-adjusted life year loss per blind individual were $4,944, $54,614, and 0.214, respectively. Combining estimates with 246,423 projected cases of blindness due to wAMD, DME, and PDR translated to total societal costs of $20 billion in 2020, estimated to triple by 2050. CONCLUSION: Excess social costs associated with blindness in individuals with wAMD, DME, and PDR are substantial, with more than half of the burden attributed to indirect costs. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:S6-S14.].

Economic-Burden Trajectories in Commercially Insured US Infants With Respiratory Syncytial Virus Infection.

BACKGROUND: This study evaluates the long-term respiratory syncytial virus (RSV) burden among preterm and full-term infants in the United States. METHODS: Infants with birth hospitalization claims and ≥24 months of continuous enrollment were retrospectively identified in the Truven MarketScan Commercial Claims and Encounters database for the period 1 January 2004-30 September 2015. Infants with RSV infection in the first year of life (n = 38 473) were matched to controls (n = 76 825), and remaining imbalances in the number of individuals in each group were adjusted using propensity score methods. All-cause, respiratory-related, and asthma/wheezing-related 5-year average cumulative costs were measured. RESULTS: Early premature (n = 213), premature (n = 397), late premature (n = 4446), and full-term (n = 33 417) RSV-infected infants were matched to 424, 791, 8875, and 66 735 controls, respectively. After 2 years since RSV diagnosis, all-cause cumulative costs for RSV-infected infants as compared to those for controls increased by $22 081 (95% confidence interval [CI], -$5800-$42 543) for early premature infants, by $14 034 (95% CI, $5095- $22 973) for premature infants, by $10 164 (95% CI, $8835-$11 493) for late premature infants, and by $5404 (95% CI, $5110-$5698) for full-term infants. The 5-year RSV burden increased to $39 490 (95% CI, $18 217-$60 764), $23 160 (95% CI, $13 002-$33 317),$13 755 (95% CI, $12 097-$15 414), and $6631 (95% CI, $6060-$7202), respectively. The RSV burden was higher when stratified by inpatient and outpatient setting and respiratory-related and asthma/wheezing-related costs. CONCLUSIONS: The RSV burden extends across cost domains and prematurity, with the greatest burden incurred by the second year of follow-up. Findings are useful in determining the cost-effectiveness of RSV therapies in development.

Long-term Assessment of Healthcare Utilization 5 Years After Respiratory Syncytial Virus Infection in US Infants.

BACKGROUND: Respiratory syncytial virus (RSV) is the primary cause of respiratory tract infections in infants; however, current burden estimates report only the short-term effects of acute infection. METHODS: Infants with RSV infection and ≥24 months of continuous enrollment were retrospectively identified from the Truven MarketScan database (1 January 2004-30 September 2015). Exposed infants (n = 38 473) were propensity score matched to nonexposed controls (n = 76 825) by baseline characteristics and gestational age. Five-year cumulative all-cause, asthma/wheezing, and respiratory event-related hospitalization rates and physician and emergency department healthcare-resource utilization rates were assessed. RESULTS: During follow-up, RSV-infected cohorts had higher average all-cause cumulative hospitalization rates, compared with controls, with values of 79.9 hospitalizations/100 patient-years (95% confidence interval [CI], 41.7-118.2) for 213 early premature infants (P < .001), 18.2 hospitalizations/100 patient-years (95% CI, .8-35.7) for 397 premature infants (P = .04), 34.2 hospitalizations/100 patient-years (95% CI, 29.1-39.2) for 4446 late premature infants (P < .001), and 16.1 hospitalizations/100 patient-years (95% CI, 14.9-17.4) for 33 417 full-term infants (P < .001). Cumulative rates of physician and emergency department visits were also higher for RSV-infected infants. Asthma/wheezing accounted for 10%-18% of total 5-year physician visits. CONCLUSIONS: Infant RSV infection has a significant long-term healthcare-resource utilization impact across gestational ages for at least 5 years after infection, most of it in the first 2 years. Systematically collecting healthcare-resource utilization data will be important for cost-effectiveness evaluations of RSV interventions in planned or ongoing trials.

Cost-Effectiveness of Sarilumab Added to Methotrexate in the Treatment of Adult Patients with Moderately to Severely Active Rheumatoid Arthritis Who Have Inadequate Response or Intolerance to Tumor Necrosis Factor Inhibitors.

BACKGROUND: Despite a substantial number of treatment options in rheumatoid arthritis (RA) following tumor necrosis factor inhibitor (TNFi) inadequate response or intolerance (TNF-IR), a lack of clarity on the optimal approach remains. Sarilumab, a human monoclonal anti-interleukin-6 receptor alpha antibody, can be used as monotherapy or in combination with methotrexate or other conventional synthetic disease-modifying anti-rheumatic drugs (DMARDs) in TNF-IR patients. OBJECTIVE: To conduct a cost-utility analysis from a U.S. health care system perspective for sarilumab subcutaneous 200 mg + methotrexate versus abatacept + methotrexate or a bundle of TNFi + methotrexate for treatment of adult patients with moderately to severely active RA and TNF-IR. METHODS: Analysis was conducted via individual patient simulation based on patient profiles from the TARGET trial (NCT01709578); a 6-month decision tree was followed by lifetime semi-Markov model with 6-month cycles. Treatment response at 6 months, informed by network meta-analysis, was based on American College of Rheumatology (ACR) 20/50/70 criteria; patients achieving ≥ ACR20 continued with current therapy, and other patients moved to the next line of biologic DMARD therapy or conventional synthetic DMARD palliative treatment. Direct costs included wholesale acquisition drug costs and administration and routine care costs. Routine care costs and quality-adjusted life-years (QALYs) were estimated by predicting the Health Assessment Questionnaire Disability Index score based on treatment response and were imputed from published equations. RESULTS: Sarilumab + methotrexate dominated the TNFi bundle + methotrexate, achieving lower costs ($319,324 vs. $356,096) and greater effectiveness (4.27 vs. 4.15 QALYs), and was on the cost-efficiency frontier with abatacept + methotrexate ($360,211 and 4.29 QALYs). Abatacept + methotrexate was not cost-effective versus sarilumab + methotrexate. Scenario analyses indicated the results were robust; sarilumab + methotrexate became dominant against abatacept + methotrexate after reduced model horizon, minimum response based on ACR50 or ACR70, or time to discontinuation per treatment class. Sarilumab + methotrexate was also dominant versus the TNFi bundle; when class-specific time to treatment discontinuation was specified, sarilumab remained cost-effective with an incremental cost-effectiveness ratio of $36,894. CONCLUSIONS: Sarilumab + methotrexate can be considered an economically dominant (more effective, less costly) option versus a second TNFi + methotrexate; compared with abatacept + methotrexate, it is a less costly but less effective option for patients with moderately to severely active RA who have previously failed TNFi. DISCLOSURES: This study was funded by Sanofi and Regeneron Pharmaceuticals. Kiss and Gal are employees of Evidera, which received consulting fees from Sanofi/Regeneron for conducting this study. Muszbek was employed by Evidera at the time of this study. Kuznik and Chen are current employees of and stockholders in Regeneron Pharmaceuticals. Fournier is an employee of and stockholder in Sanofi. Proudfoot is a former employee of and current stockholder in Sanofi and current employee and stockholder in ViiV Healthcare/GlaxoSmithKline. Michaud has received grant funding from Pfizer and the Rheumatology Research Foundation. The sponsors were involved in the study design, collection, analysis, and interpretation of data as well as data checking of information provided in the manuscript. The authors had unrestricted access to study data, were responsible for all content and editorial decisions, and received no honoraria related to the development of this publication.

Dupilumab Versus Cyclosporine for the Treatment of Moderate-to-Severe Atopic Dermatitis in Adults: Indirect Comparison Using the Eczema Area and Severity Index.

Dupilumab is approved for uncontrolled moderate-to-severe atopic dermatitis (AD); cyclosporine is approved for severe AD for ≤ 1 year. The efficacy/effectiveness of these treat-ments was compared indirectly. Regression models used pooled patient-level data to estimate response (Eczema Area and Severity Index (EASI) EASI-50/EASI-75 at weeks 12-16 and 24-30) to dupilumab 300 mg every 2 weeks (CHRONOS [NCT02260986]) or cyclosporine (University Medical Center). Models were adjusted for sex, baseline EASI, and thymus and activation-regulated chemokine level. A total of 106 patients received dupilumab (+ topical cortico-steroids; + TCS), and 57 received cyclosporine (+ TCS). Among University Medical Center patients, estimated EASI-50 responders were, dupilumab vs. cyclosporine, 91% vs. 77% (p = 0.038; weeks 12-16), and 96% vs. 67% (p < 0.0001; weeks 24-30); EASI-75 responders were 78% vs. 56% (p = 0.016; weeks 12-16) and 80% vs. 47% (p <0.001; weeks 24-30). Among CHRONOS patients, estimated EASI-50 responders were 90% vs. 74% (p <0.038; weeks 12-16) and 92% vs. 53% (p < 0.0001; weeks 24-30); EASI-75 responders were 75% vs. 52% (p = 0.016; weeks 12-16) and 74% vs. 40% (p <0.001; weeks 24-30), respectively. These results suggest a higher relative efficacy of dupilumab vs. cyclosporine.

Economic Evaluation of Sarilumab in the Treatment of Adult Patients with Moderately-to-Severely Active Rheumatoid Arthritis Who Have an Inadequate Response to Conventional Synthetic Disease-Modifying Antirheumatic Drugs.

INTRODUCTION: Assess the cost-effectiveness (US healthcare payer perspective) of sarilumab subcutaneous (SC) 200 mg + methotrexate versus conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs) or targeted DMARD + methotrexate for moderate-to-severe rheumatoid arthritis (RA) in adults with inadequate response to methotrexate. METHODS: Microsimulation based on patient profiles from MOBILITY (NCT01061736) was conducted via a 6-month decision tree and lifetime Markov model with 6-monthly cycles. Treatment response at 6 months was informed by a network meta-analysis and based on American College of Rheumatology (ACR) response. Responders: patients with ACR20 response who continued with therapy; non-responders: ACR20 non-responders who transitioned to the subsequent treatment. Utilities and quality-adjusted life-years (QALYs) were estimated via mapping 6-month ACR20/50/70 response to relative change in Health Assessment Questionnaire Disability Index score (short term) and based on published algorithms (long term). Direct costs considered drugs (wholesale acquisition costs), administration and routine care. RESULTS: Lifetime QALYs and costs for treatment sequences on the efficiency frontier were 3.43 and $115,019 for active csDMARD, 5.79 and $430,918 for sarilumab, and 5.94 and $524,832 for etanercept (all others dominated). Sarilumab was cost-effective versus tocilizumab and csDMARD (incremental cost-effectiveness ratios of $84,079/QALY and $134,286/QALY). Probabilistic sensitivity analysis suggested comparable costs and slightly improved health benefits for sarilumab versus tocilizumab, irrespective of threshold. CONCLUSION: In patients with moderate-to-severe RA, sarilumab 200 mg SC every 2 weeks + methotrexate can be considered a cost-effective treatment option, with lower costs and greater health benefits than alternative treatment sequences (+ methotrexate) beginning with adalimumab, certolizumab, golimumab and tofacitinib and below commonly accepted cost-effectiveness thresholds against tocilizumab + methotrexate or csDMARD active treatment. FUNDING: Sanofi and Regeneron Pharmaceuticals, Inc.

Indirect Treatment Comparison of the Efficacy and Safety of Sarilumab Monotherapy in Rheumatoid Arthritis Patients with Inadequate Response to Conventional Disease-Modifying Antirheumatic Drugs.

INTRODUCTION: To evaluate the comparative efficacy and safety of subcutaneous sarilumab 200 mg monotherapy administered every 2 weeks (q2w) versus other monotherapies of biologic, targeted and conventional synthetic disease-modifying antirheumatic drugs (bDMARDs, tsDMARDs, csDMARDs) at recommended doses for treatment of rheumatoid arthritis in patients who are intolerant of or inadequate responders to csDMARDs (csDMARD-IR). METHODS: A systematic literature review and network meta-analysis (NMA) were conducted on 24-week efficacy outcomes: Health Assessment Questionnaire Disability Index (HAQ-DI) score, American College of Rheumatology (ACR) 20/50/70 criteria, and European League Against Rheumatism Disease Activity Score 28-joint count erythrocyte sedimentation rate (DAS28) < 2.6. In addition, serious infections and serious adverse events (SI/SAE) were examined at 24 weeks. RESULTS: Nine trials were selected for the NMA. Sarilumab 200 mg showed superiority versus adalimumab monotherapy on all efficacy outcomes and versus tofacitinib monotherapy on ACR20. Compared with csDMARDs, sarilumab 200 mg showed superiority on ACR 20/50/70 criteria and DAS28 < 2.6 but had similar efficacy on HAQ-DI. Efficacy of sarilumab 200 mg was similar versus certolizumab, etanercept, tofacitinib and tocilizumab 8 mg/kg monotherapy across all efficacy outcomes. SI/SAE appeared similar for sarilumab 200 mg versus all comparators. CONCLUSION: In csDMARD-IR patients, sarilumab 200 mg monotherapy has superior efficacy and similar safety versus csDMARDs, superior efficacy and similar safety versus adalimumab, and similar efficacy and safety versus bDMARDs and tsDMARDs. FUNDING: Sanofi and Regeneron Pharmaceuticals, Inc.