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%.

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.

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.

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.

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.

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.

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.

Cost-optimization in the treatment of multidrug resistant tuberculosis in Nigeria.

OBJECTIVE: To compare the cost of facility-based MDR TB care (F) to home-based care (H) from the perspective of the Nigerian national health system. METHODS: We assessed the expected costs of the two MDR TB treatment approaches using a decision-analytic model with a follow-up of 6 months. MDR TB treatment outcomes were obtained from a systematic review of randomised clinical trials. The outcomes of interest included treatment success, treatment failure, treatment default and mortality and did not vary significantly between the two alternatives. Treatment costs included the cost of the following: drug therapy (F, H), hospital stay (F), nurse care (F, H), physician care (F), nursing facility (F) and transport to the healthcare provider (H). Finally, we estimated the potential cost savings associated with home-based treatment for all patients starting MDR TB treatment in Nigeria. RESULTS: The average expected total treatment cost for a Nigerian patient treated for MDR TB was estimated at US2095 for facility - based care and 1535 for home-based care, a potential saving of 25%. One of the major drivers of this difference is significantly more intensive, and therefore more costly, nursing care in hospitals. In 2013, a total of 426 patients were initiated on facility-based MDR TB treatment in Nigeria. Thus, the potential savings through home-based care are US$ 223 204 per year. CONCLUSION: In Nigeria, treatment of MDR TB using home-based care is expected to result in similar patient outcomes at markedly reduced public health costs as facility-based care.

Newborn screening and prophylactic interventions for sickle cell disease in 47 countries in sub-Saharan Africa: a cost-effectiveness analysis.

BACKGROUND: Sickle cell disease (SCD) constitutes a major public health problem in sub-Saharan Africa (SSA). Newborn screening and early subsequent clinical intervention can reduce early mortality and increase life expectancy, but have not been widely implemented in SSA. This analysis assesses the cost-effectiveness of a newborn screening and prophylactic intervention (NSPI) package for SCD in 47 SSA countries. METHODS: A lifetime Markov model with annual cycles was built with infants either being screened using isoelectric focusing (IEF) or not screened. Confirmed positive cases received interventions including insecticide-treated mosquito bed nets, folic acid supplementation, prophylactic antimalarial and penicillin therapy, and vaccinations against bacterial infections. Estimates for the local incidence of SCD, the life expectancy of untreated children, the SCD disability weight, and the cost of screening laboratory tests were based on published sources. Among treated infants, the annual probability of mortality until 30 years of age was derived from a pediatric hospital-based cohort. The outcome of interest included a country-specific cost per Disability Adjusted Life Year (DALY) averted. RESULTS: Of 47 modeled countries in SSA, NSPI is almost certainly highly cost-effective in 24 countries (average cost per DALY averted: US$184); in 10 countries, it is cost-effective in the base case (average cost per DALY averted: US$285), but the results are subject to uncertainty; in the remaining 13, it is most likely not cost-effective. We observe a strong inverse relationship between the incidence rate of SCD and the cost per DALY averted. Newborn screening is estimated to be cost-effective as long as the incidence rate exceeds 0.2-0.3 %, although in some countries NSPI is cost-effective at incidence rates below this range. In total, NSPI could avert over 2.4 million disability adjusted life years (DALYs) annually across SSA. CONCLUSIONS: Using IEF to screen all newborns for SCD plus administration of prophylactic interventions to affected children is cost-effective in the majority of countries in SSA.

Estimating the Public Health Burden Associated With Adverse Pregnancy Outcomes Resulting From Syphilis Infection Across 43 Countries in Sub-Saharan Africa.

BACKGROUND: Untreated syphilis in pregnancy is associated with adverse clinical outcomes to the infant. The study aimed to estimate the public health burden resulting from adverse pregnancy outcomes due to syphilis infection among pregnant women not screened for syphilis in 43 countries in sub-Saharan Africa. METHODS: Estimated country-specific incidence of syphilis was generated from annual number of live births, the proportion of women with at least 1 antenatal care (ANC) visit, the syphilis prevalence rate, and the proportion of women screened for syphilis during ANC.Adverse pregnancy outcome data (stillbirth, neonatal death, low birth weight, and congenital syphilis) were obtained from published sources. Disability-adjusted life-year (DALY) estimates were calculated using undiscounted local life expectancy, the neonatal standard loss function, and relevant disability weights. The model assessed the potential impact of raising ANC coverage to at least 95% and syphilis screening to at least 95% (World Health Organization targets). RESULTS: For all 43 sub-Saharan Africa countries, the estimated incidence of adverse pregnancy outcomes was 205,901 (95% confidence interval [CI], 113,256-383,051) per year, including stillbirth (88,376 [95% CI, 60,854-121,713]), neonatal death (34,959 [95% CI, 23,330-50,076]), low birth weight (22,483 [95% CI, 0-98,847]), and congenital syphilis (60,084 [95% CI, 29,073-112,414]), resulting in approximately 12.5 million DALYs. Countries with the greatest burden are (in DALYs, millions) Democratic Republic of the Congo (1.809), Nigeria (1.598), Ethiopia (1.466), and Tanzania (0.961). Attaining World Health Organization targets could reduce the burden by 8.5 million DALYs. CONCLUSIONS: Substantial infant mortality and morbidity results from maternal syphilis infection concentrated in countries with low access to ANC or low rates of syphilis screening.

Comparison of costs and discharge outcomes for patients hospitalized for ischemic or hemorrhagic stroke with or without atrial fibrillation in the United States.

This retrospective analysis investigated the impact of baseline clinical characteristics, including atrial fibrillation (AF), on hospital discharge status (to home or continuing care), mortality, length of hospital stay, and treatment costs in patients hospitalized for stroke. The analysis included adult patients hospitalized with a primary diagnosis of ischemic or hemorrhagic stroke between January 2006 and June 2011 from the premier alliance database, a large nationally representative database of inpatient health records. Patients included in the analysis were categorized as with or without AF, based on the presence or absence of a secondary listed diagnosis of AF. Irrespective of stroke type (ischemic or hemorrhagic), AF was associated with an increased risk of mortality during the index hospitalization event, as well as a higher probability of discharge to a continuing care facility, longer duration of stay, and higher treatment costs. In patients hospitalized for a stroke event, AF appears to be an independent risk factor of in-hospital mortality, discharge to continuing care, length of hospital stay, and increased treatment costs.

Cost-effectiveness of apixaban vs. current standard of care for stroke prevention in patients with atrial fibrillation.

AIMS: Warfarin, a vitamin K antagonist (VKA), has been the standard of care for stroke prevention in patients with atrial fibrillation (AF). Aspirin is recommended for low-risk patients and those unsuitable for warfarin. Apixaban is an oral anticoagulant that has demonstrated better efficacy than warfarin and aspirin in the ARISTOTLE and AVERROES studies, respectively, and causes less bleeding than warfarin. We evaluated the potential cost-effectiveness of apixaban against warfarin and aspirin from the perspective of the UK payer perspective. RESULTS AND METHODS: A lifetime Markov model was developed to evaluate the pharmacoeconomic impact of apixaban compared with warfarin and aspirin in VKA suitable and VKA unsuitable patients, respectively. Clinical events considered in the model include ischaemic stroke, haemorrhagic stroke, intracranial haemorrhage, other major bleed, clinically relevant non-major bleed, myocardial infarction, cardiovascular hospitalization and treatment discontinuations; data from the ARISTOTLE and AVERROES trials and published mortality rates and event-related utility rates were used in the model. Apixaban was projected to increase life expectancy and quality-adjusted life years (QALYs) compared with warfarin and aspirin. These gains were expected to be achieved at a drug acquisition-related cost increase over lifetime. The estimated incremental cost-effectiveness ratio was £11 909 and £7196 per QALY gained with apixaban compared with warfarin and aspirin, respectively. Sensitivity analyses indicated that results were robust to a wide range of inputs. CONCLUSIONS: Based on randomized trial data, apixaban is a cost-effective alternative to warfarin and aspirin, in VKA suitable and VKA unsuitable patients with AF, respectively.

Cost-Effectiveness of Dolutegravir Compared With Efavirenz for Prevention of Perinatal Transmission in Women Presenting With HIV in Late Pregnancy in Uganda.

OBJECTIVES: Dolutegravir (DTG) has proved to be more efficacious, tolerable, and safer than efavirenz (EFV) among mothers living with HIV and their infants in Uganda. This study assessed the cost-effectiveness of the DTG-based antiretroviral therapy (ART) compared with the standard of care for preventing perinatal transmissions among pregnant women initiating ART in late pregnancy in Uganda. METHODS: We used data from a randomized open-label trial (DolPHIN-2) and a 2-part cost-effectiveness model composed of a short-term decision tree to estimate the perinatal transmission rate and costs and an individual-based 3-state Markov model (HIV, advanced HIV, dead) to estimate the long-term costs and health outcomes from the Ugandan payer perspective using a lifetime horizon and a 1-year Markov cycle. The main outcomes were the mean annual costs in US dollars ($), disability-adjusted life-years (DALYs), and incremental cost-effectiveness ratio. Both the deterministic and probabilistic sensitivity analyses were conducted to assess the effect of parameter uncertainties on the ultimate results and the model's robustness. RESULTS: Compared with the EFV-based ART, the DTG-based ART was associated with fewer mean annual costs ($43.58 vs $68.44) and DALYs (0.33 vs 0.56), leading to cost savings of $110 per DALY averted. In the incremental analysis, the DTG-based ART dominated the EFV-based ART; that is, it was less costly and more effective. These results were robust to deterministic and probabilistic sensitivity analyses. CONCLUSION: The DTG-based ART is a highly cost-effective strategy compared with the EFV-based ART among women initiating treatment in the third trimester of pregnancy in a low-income setting.

Antenatal syphilis screening using point-of-care testing in Sub-Saharan African countries: a cost-effectiveness analysis.

BACKGROUND: Untreated syphilis in pregnancy is associated with adverse clinical outcomes for the infant. Most syphilis infections occur in sub-Saharan Africa (SSA), where coverage of antenatal screening for syphilis is inadequate. Recently introduced point-of-care syphilis tests have high accuracy and demonstrate potential to increase coverage of antenatal screening. However, country-specific cost-effectiveness data for these tests are limited. The objective of this analysis was to evaluate the cost-effectiveness and budget impact of antenatal syphilis screening for 43 countries in SSA and estimate the impact of universal screening on stillbirths, neonatal deaths, congenital syphilis, and disability-adjusted life years (DALYs) averted. METHODS AND FINDINGS: The decision analytic model reflected the perspective of the national health care system and was based on the sensitivity (86%) and specificity (99%) reported for the immunochromatographic strip (ICS) test. Clinical outcomes of infants born to syphilis-infected mothers on the end points of stillbirth, neonatal death, and congenital syphilis were obtained from published sources. Treatment was assumed to consist of three injections of benzathine penicillin. Country-specific inputs included the antenatal prevalence of syphilis, annual number of live births, proportion of women with at least one antenatal care visit, per capita gross national income, and estimated hourly nurse wages. In all 43 sub-Saharan African countries analyzed, syphilis screening is highly cost-effective, with an average cost/DALY averted of US$11 (range: US$2-US$48). Screening remains highly cost-effective even if the average prevalence falls from the current rate of 3.1% (range: 0.6%-14.0%) to 0.038% (range: 0.002%-0.113%). Universal antenatal screening of pregnant women in clinics may reduce the annual number of stillbirths by up to 64,000, neonatal deaths by up to 25,000, and annual incidence of congenital syphilis by up to 32,000, and avert up to 2.6 million DALYs at an estimated annual direct medical cost of US$20.8 million. CONCLUSIONS: Use of ICS tests for antenatal syphilis screening is highly cost-effective in SSA. Substantial reduction in DALYs can be achieved at a relatively modest budget impact. In SSA, antenatal programs should expand access to syphilis screening using the ICS test. Please see later in the article for the Editors' Summary.

Evaluation of cardiovascular disease burden and therapeutic goal attainment in US adults with chronic kidney disease: an analysis of national health and nutritional examination survey data, 2001-2010.

BACKGROUND: For chronic kidney disease (CKD) patients, national treatment guidelines recommend a low-density lipoprotein cholesterol (LDL-C) goal <100 mg/dL and blood pressure (BP) target <130/80 mmHg. This analysis assessed the current status of cardiovascular (CV) risk factor treatment and control in US adults with CKD. METHODS: Weighted prevalence estimates of CV-related comorbidities, utilization of lipid- and BP-lowering agents, and LDL-C and BP goal attainment in US adults with CKD were assessed among 9,915 men and nonpregnant women aged ≥20 years identified from the fasting subsample of the 2001-2010 National Health and Nutritional Examination Survey (NHANES). Analyses were performed using SAS survey procedures that consider the complex, multistage, probability sampling design of NHANES. All estimates were standardized to the 2008 US adult population (≥20 years). Data were stratified by CKD stage based on presence of albuminuria and estimated glomerular filtration rate (eGFR), calculated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation. Stage 3 CKD was subdivided into 3a (eGFR 45-59 mL/min/1.73 m(2)) and 3b (eGFR 30-44 mL/min/1.73 m(2)); Stage 5 CKD and dialysis recipients were excluded. RESULTS: Of the 9,915 NHANES participants identified for analysis, 1,428 had CKD (Stage 1-4), corresponding to a prevalence estimate for US adults aged ≥20 years of 10.2%. Prevalence of CV-related comorbidities increased markedly with CKD stage, with a ~6-12-fold increase in cardiovascular disease, coronary heart disease (CHD), stroke and congestive heart failure between CKD Stage 1 and 4; prevalence of diabetes, hyperlipidemia and hypertension increased by ~1.2-1.6-fold. Use of lipid-lowering agents increased with CKD stage, from 18.1% (Stage 1) to 44.8% (Stage 4). LDL-C goal attainment increased from 35.8% (Stage 1) to 52.8% (Stage 3b), but decreased in Stage 4 (50.7%). BP goal attainment decreased between Stage 1 and 4 (from 49.5% to 30.2%), despite increased use of antihypertensives (from 30.2% to 78.9%). CONCLUSIONS: Individuals with CKD have a high prevalence of CV-related comorbidities. However, attainment of LDL-C or BP goals was low regardless of disease stage. These findings highlight the potential for intensive risk factor modification to maximize CV event reduction in CKD patients at high risk for CHD.

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.

Evaluating the cost-effectiveness of combination antiretroviral therapy for the prevention of mother-to-child transmission of HIV in Uganda.

OBJECTIVE: To model the cost-effectiveness in Uganda of combination antiretroviral therapy (ART) to prevent mother-to-child transmission of human immunodeficiency virus (HIV). METHODS: The cost-effectiveness of ART was evaluated on the assumption that ART reduces the risk of an HIV-positive pregnant woman transmitting HIV to her baby from 40% (when the woman is left untreated) to 25.8%, 17.4% and 3.8%, respectively, when the woman is given: (i) single-dose nevirapine (at an estimated total drug cost of 0.06 United States dollars [US$]); (ii) dual therapy with zidovudine and lamivudine for 7 weeks (at a total drug cost of US$ 15.63); or (iii) ART for 18 months (at a total annual cost of US$ 469.77). Lifetime ART (US$ 6883), recommended for pregnant women with < 350 CD4+ T lymphocytes per mm(3), was assumed to give the same reduction in transmission risk in each subsequent pregnancy. FINDINGS: Compared with single-dose nevirapine, dual therapy and no therapy, 18 months of ART averted 5.21, 3.22 and 8.58 disability-adjusted life years (DALYs), respectively, at a cost of US$ 46, US$ 99 and US$ 34 per DALY averted. The corresponding figures for lifetime ART are, respectively, 19.20, 11.87 and 31.60 DALYs averted, at a cost of US$ 205, US$ 354 and US$ 172 per DALY averted. CONCLUSION: In Uganda, ART appears highly cost-effective for the prevention of mother-to-child HIV transmission, even if continued over the patients' lifetimes. Given the additional public health benefits of ART, efforts to ensure that all HIV-positive pregnant women have access to lifelong ART should be intensified.

Cost-effectiveness of early initiation of first-line combination antiretroviral therapy in Uganda.

BACKGROUND: Ugandan national guidelines recommend initiation of combination antiretroviral therapy (cART) at CD4+ T cell (CD4) count below 350 cell/µl, but the implementation of this is limited due to availability of medication. However, cART initiation at higher CD4 count increases survival, albeit at higher lifetime treatment cost. This analysis evaluates the cost-effectiveness of initiating cART at a CD4 count between 250-350 cell/µl (early) versus <250 cell/µl (delayed). METHODS: Life expectancy of cART-treated patients, conditional on baseline CD4 count, was modeled based on published literature. First-line cART costs $192 annually, with an additional $113 for patient monitoring. Delaying initiation of cART until the CD4 count falls below 250 cells/µl would incur the cost of the bi-annual CD4 count tests and routine maintenance care at $85 annually. We compared lifetime treatment costs and disability adjusted life-expectancy between early vs. delayed cART for ten baseline CD4 count ranges from 250-350 cell/µl. All costs and benefits were discounted at 3% annually. RESULTS: Treatment delay varied from 6-18 months. Early cART initiation increased life expectancy from 1.5-3.5 years and averted 1.33-3.10 disability adjusted life years (DALY's) per patient. Lifetime treatment costs were $4,300-$5,248 for early initiation and $3,940-$4,435 for delayed initiation. The cost/DALY averted of the early versus delayed start ranged from $260-$270. CONCLUSIONS: In HIV-positive patients presenting with CD4 count between 250-350 cells/µl, immediate initiation of cART is a highly cost-effective strategy using the recommended one-time per capita GDP threshold of $490 reported for Uganda. This would constitute an efficient use of scarce health care funds.

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.

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.