Health care resource utilization and costs for treatment-experienced people with HIV switching or restarting antiretroviral regimens since 2018.

BACKGROUND: There is a need to understand health care resource utilization (HCRU) and costs associated with treatment-experienced people with HIV (PWH) switching treatment regimens. OBJECTIVE: To describe HCRU and cost during lines of antiretroviral therapy (ART) for treatment-experienced PWH switching to or restarting guideline-recommended, integrase strand transfer inhibitor (INSTI)-based multitablet regimens and single-tablet regimens. METHODS: This retrospective claims study used data from Optum Research Database (January 1, 2010, to March 31, 2020) to identify lines of therapy (LOTs) for treatment-experienced adults who switched to or restarted INSTI-based regimens between January 1, 2018, and December 31, 2019. The first LOT during the study period was included in the analysis. We examined all-cause HCRU and costs and HIV-related HCRU and combined costs to the health plan and direct patient costs by site of service and compared between INSTI-based regimens: bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) (single tablet) vs dolutegravir/abacavir/lamivudine (DTG/ABC/3TC) (single tablet), dolutegravir + emtricitabine/tenofovir alafenamide (DTG+FTC/TAF) (multitablet), and dolutegravir + emtricitabine/tenofovir disoproxil fumarate (DTG+FTC/TDF) (multitablet). Analysis of HCRU by site of service was conducted following inverse probability treatment weighting. Multivariable regression was conducted using a generalized linear model with stepwise covariate selection to estimate HIV-related medical costs and control for remaining differences after inverse probability treatment weighting. RESULTS: 4,251 PWH were identified: B/F/TAF (n = 2,727; 64.2%), DTG/ABC/3TC (n = 898; 21.1%), DTG+FTC/TAF (n = 539; 12.7%), and DTG+FTC/TDF (n = 87; 2.1%). PWH treated with DTG+FTC/TAF had a significantly higher mean of all-cause ambulatory visits than PWH treated with B/F/TAF (1.8 vs 1.6, P < 0.001). A significantly smaller proportion of PWH treated with DTG/ABC/3TC had an all-cause ambulatory visit vs PWH treated with B/F/TAF (90.6% vs 93.9%, P < 0.001). All-cause total costs were not significantly different between regimens. Mean (SD) medical HIV-related costs per month during the LOT were not significantly different between B/F/TAF $699 (3,602), DTG/ABC/3TC $770 (3,469), DTG+FTC/TAF $817 (3,128), and DTG+FTC/TDF $3,570 (17,691). After further controlling for unbalanced measures, HIV-related medical costs during the LOT were higher (20%) but did not reach statistical significance for DTG/ABC/3TC (cost ratio = 1.20, 95% CI = 0.851-1.694; P = 0.299), 49% higher for DTG+FTC/TAF (cost ratio = 1.489, 95% CI = 1.018-2.179; P = 0.040), and almost 11 times greater for DTG+FTC/TDF (cost ratio = 10.759, 95% CI = 2.182-53.048; P = 0.004) compared with B/F/TAF. CONCLUSIONS: HIV-related medical costs during the LOT were lowest for PWH treated with INSTI-based single-tablet regimens. Simplifying treatment regimens may help PWH maintain lower health care costs.

Potential healthcare resource use and associated costs of every 2 month injectable cabotegravir plus rilpivirine long-acting regimen implementation in the Spanish National Healthcare System compared to daily oral HIV treatments.

INTRODUCTION: HIV treatment currently consists of daily oral antiretroviral therapy (ART). Cabotegravir + rilpivirine long-acting (CAB + RPV LA) is the first ART available in Spain administered every 2 months through intramuscular injection by a healthcare professional (HCP). The objective of this analysis was to assess potential healthcare resource use (HRU) and cost impact of implementing CAB + RPV LA vs. daily oral ART at National Health System (NHS) hospitals. METHODS: Online quantitative interviews and cost analysis were performed. Infectious disease specialists (IDS), hospital pharmacists (HP) and nurses were asked about their perception of potential differences in HRU between CAB + RPV LA vs. daily oral ART, among other concepts of interest. Spanish official tariffs were applied as unit costs to the HRU estimates (€2022). RESULTS: 120 responders (n = 40 IDS, n = 40 HP, n = 40 nurses) estimated an average number of annual visits per patient by speciality (IDS, HP, and nurse, respectively) of 3.3 vs. 3.7; 4.4 vs. 6.2; 6.1 vs. 3.9, for CAB + RPV LA vs. daily oral ART, and 3.0 vs. 3.2; 4.8 vs. 5.8; 6.9 vs. 4.9, respectively when adjusting by corresponding specialist responses. Estimation by the total sample led to an annual total cost per patient of €2,076 vs. €2,473, being €2,032 vs. €2,237 after adjusting by corresponding HCP, for CAB + RPV LA vs. daily oral ART. CONCLUSIONS: These results suggest that the implementation of CAB + RPV LA in NHS hospitals would not incur in increased HRU-related costs compared to current daily oral ARTs, being potentially neutral or even cost-saving.

Cost-Effectiveness and Budget Impact Analysis of Apixaban and Rivaroxaban Versus Warfarin in the Prevention of Stroke in Patients With Non-Valvular Atrial Fibrillation (NVAF) in Iran.

INTRODUCTION: This study evaluates the cost-effectiveness of Apixaban and Rivaroxaban, compared to Warfarin, for stroke prevention in patients with non-valvular atrial fibrillation in Iran. METHOD: A Markov model with a 30-year time horizon was employed to simulate and assess different treatment strategies' cost-effectiveness. The study population comprised Iranian adults with NVAF, identified through specialist consultations, hospital visits, and archival record reviews. Direct medical costs, direct nonmedical, and indirect costs were included. Quality-adjusted life years (QALY) were assessed using an EQ-5D questionnaire. This study utilized a cost-effectiveness threshold of $11 134 per QALY. RESULTS: Apixaban demonstrated superior cost-effectiveness compared to Rivaroxaban and Warfarin. Over 30 years, total costs were lower in the Apixaban and Rivaroxaban groups compared to the Warfarin group ($126.18 and $109.99 vs. $150.49). However, Apixaban showed higher total QALYs gained compared to others (0.134 vs. 0.133 and 0.116). The incremental cost-effectiveness ratio for comparing Apixaban to Warfarin was calculated at -1332.83 cost per QALY, below the threshold of $11 134, indicating Apixaban's cost-effectiveness. Sensitivity analyses confirmed the robustness of the findings, with ICER consistently remaining below the threshold. Over 5 years (2024-2028) of Apixaban usage, the incremental cost starts at USD 70 250 296 in the first year and gradually rises to USD 71 770 662 in the fifth year. DSA and PSA were assessed to prove the robustness of the results. CONCLUSION: This study shows that Apixaban is a cost-effective option for stroke prevention in non-valvular atrial fibrillation patients in Iran compared to Warfarin.

Costs and acceptability of simplified monitoring in HIV-suppressed patients switching to dual therapy: the SIMPL'HIV open-label, factorial randomised controlled trial.

BACKGROUND: Clinical and laboratory monitoring of patients on antiretroviral therapy is an integral part of HIV care and determines whether treatment needs enhanced adherence or modification of the drug regimen. However, different monitoring and treatment strategies carry different costs and health consequences. MATERIALS AND METHODS: The SIMPL'HIV study was a randomised trial that assessed the non-inferiority of dual maintenance therapy. The co-primary outcome was a comparison of costs over 48 weeks of dual therapy with standard antiretroviral therapy and the costs associated with a simplified HIV care approach (patient-centred monitoring [PCM]) versus standard, tri-monthly routine monitoring. Costs included outpatient medical consultations (HIV/non-HIV consultations), non-medical consultations, antiretroviral therapy, laboratory tests and hospitalisation costs. PCM participants had restricted immunological and blood safety monitoring at weeks 0 and 48, and they were offered the choice to complete their remaining study visits via a telephone call, have medications delivered to a specified address, and to have blood tests performed at a location of their choice. We analysed the costs of both strategies using invoices for medical consultations issued by the hospital where the patient was followed, as well as those obtained from health insurance companies. Secondary outcomes included differences between monitoring arms for renal function, lipids and glucose values, and weight over 48 weeks. Patient satisfaction with treatment and monitoring was also assessed using visual analogue scales. RESULTS: Of 93 participants randomised to dolutegravir plus emtricitabine and 94 individuals to combination antiretroviral therapy (median nadir CD4 count, 246 cells/mm3; median age, 48 years; female, 17%),patient-centred monitoring generated no substantial reductions or increases in total costs (US$ -421 per year [95% CI -2292 to 1451]; p = 0.658). However, dual therapy was significantly less expensive (US$ -2620.4 [95% CI -2864.3 to -2331.4]) compared to standard triple-drug antiretroviral therapy costs. Approximately 50% of participants selected one monitoring option, one-third chose two, and a few opted for three. The preferred option was telephone calls, followed by drug delivery. The number of additional visits outside the study schedule did not differ by type of monitoring. Patient satisfaction related to treatment and monitoring was high at baseline, with no significant increase at week 48. CONCLUSIONS: Patient-centred monitoring did not reduce costs compared to standard monitoring in individuals switching to dual therapy or those continuing combined antiretroviral therapy. In this representative sample of patients with suppressed HIV, antiretroviral therapy was the primary factor driving costs, which may be reduced by using generic drugs to mitigate the high cost of lifelong HIV treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT03160105.

[Administrative delays of temporary recommendation for use: Impact on access to innovation in melanoma]. / Délais administratifs des RTU, effet sur l'accès à l'innovation dans le mélanome.

INTRODUCTION: Melanoma has benefited in recent years from therapeutic innovations, which have improved overall survival of patients. France has developed a regulatory arsenal allowing faster access to innovative drugs before marketing authorization: temporary authorization for use (ATU) and temporary recommendation for use (RTU). METHOD: We describe here the decision-making processes that led to the non-publication of the decree on the funding of three RTU in adjuvant melanoma therapy: nivolumab, pembrolizumab and the combination of dabrafenib and trametinib, and we analyse the fate of these drugs in order to quantify the potential loss of chance. RESULTS: On 03AUG2018, the French National Agency for Medicines and Health Product Safety (ANSM) published 3 RTU in order to give rapid access to major innovations in adjuvant melanoma therapy: nivolumab, pembrolizumab and the combination of dabrafenib and trametinib. These drugs have respectively demonstrated reductions in the risk of recurrence by 35 %, 43% and 55% for target populations of 2200, 1900 and 650 patients per year. Despite a favourable opinion on reimbursement from the French National Authority for Health (HAS), the decrees on reimbursement will never be published, prohibiting the use of these products before the marketing authorisation, and depriving many patients of a potential cure. CONCLUSION: Despite a favourable opinion from scientists and health agencies for the rapid availability of a drug, the French public health code does not systematically imply access to a therapeutic innovation. The reform of access to innovation implemented on 01JUL2021 may help tackle this issue.

Cost-effectiveness of the anti-fibrotics for the treatment of idiopathic pulmonary fibrosis in the United States.

BACKGROUND: The anti-fibrotic medications nintedanib and pirfenidone were approved in the United States for use in patients with idiopathic pulmonary fibrosis several years ago. While there is a growing body of evidence surrounding their clinical effectiveness, these medications are quite expensive and no prior cost-effectiveness analysis has been performed in the United States. METHODS: A previously published Markov model performed in the United Kingdom was replicated using United States data to project the lifetime costs and health benefits of treating idiopathic pulmonary fibrosis with: (1) symptom management; (2) pirfenidone; or (3) nintedanib. For the cost-effectiveness analysis, strategies were ranked by increasing costs and then checked for dominating treatment strategies. Then an incremental cost-effectiveness ratio was calculated for the dominant therapy. RESULTS: The anti-fibrotic medications were found to cost more than $110,000 per year compared to $12,291 annually for symptom management. While pirfenidone was slightly more expensive than nintedanib and provided the same amount of benefit, neither medication was found to be cost-effective in this U.S.-based analysis, with an average cost of $1.6 million to gain one additional quality-adjusted life year over symptom management. CONCLUSIONS: Though the anti-fibrotics remain the only effective treatment option for patients with idiopathic pulmonary fibrosis and the data surrounding their clinical effectiveness continues to grow, they are not considered cost-effective treatment strategies in the United States due to their high price.

Cost-effectiveness analysis of apixaban versus vitamin K antagonists for antithrombotic therapy in patients with atrial fibrillation after acute coronary syndrome or percutaneous coronary intervention in Spain.

BACKGROUND/OBJECTIVE: AUGUSTUS trial demonstrated that, for patients with atrial fibrillation (AF) having acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI), an antithrombotic regimen with apixaban and P2Y12 resulted in less bleeding, fewer hospitalizations, and similar ischemic events than regimens including a vitamin K antagonist (VKA), aspirin, or both. This study objective was to evaluate long-term health and economic outcomes and the cost-effectiveness of apixaban over VKA, as a treatment option for patients with AF having ACS/PCI. METHODS: A lifetime Markov cohort model was developed comparing apixaban versus VKA across multiple treatment strategies (triple [with P2Y12 + aspirin] or dual [with P2Y12] therapy followed by monotherapy [apixaban or VKA]; triple followed by dual and then monotherapy; dual followed by monotherapy). The model adopted the Spanish healthcare perspective, with a 3-month cycle length and costs and health outcomes discounted at 3%. RESULTS: Treatment with apixaban resulted in total cost savings of €883 and higher life years (LYs) and quality-adjusted LYs (QALYs) per patient than VKA (net difference, LYs: 0.13; QALYs: 0.11). Bleeding and ischemic events (per 100 patients) were lower with apixaban than VKA (net difference, -13.9 and -1.8, respectively). Incremental net monetary benefit for apixaban was €3,041, using a willingness-to-pay threshold of €20,000 per QALY. In probabilistic sensitivity analysis, apixaban was dominant in the majority of simulations (92.6%), providing additional QALYs at lower costs than VKA. CONCLUSIONS: Apixaban was a dominant treatment strategy than VKA from both the Spanish payer's and societal perspectives, regardless of treatment strategy considered.

Pirfenidone vs. nintedanib in patients with idiopathic pulmonary fibrosis: a retrospective cohort study.

BACKGROUND: Two antifibrotic drugs, pirfenidone and nintedanib, are licensed for the treatment of patients with idiopathic pulmonary fibrosis (IPF). However, there is neither evidence from prospective data nor a guideline recommendation, which drug should be preferred over the other. This study aimed to compare pirfenidone and nintedanib-treated patients regarding all-cause mortality, all-cause and respiratory-related hospitalizations, and overall as well as respiratory-related health care costs borne by the Statutory Health Insurance (SHI). METHODS: A retrospective cohort study with SHI data was performed, including IPF patients treated either with pirfenidone or nintedanib. Stabilized inverse probability of treatment weighting (IPTW) based on propensity scores was applied to adjust for observed covariates. Weighted Cox models were estimated to analyze mortality and hospitalization. Weighted cost differences with bootstrapped 95% confidence intervals (CI) were applied for cost analysis. RESULTS: We compared 840 patients treated with pirfenidone and 713 patients treated with nintedanib. Both groups were similar regarding two-year all-cause mortality (HR: 0.90 95% CI: 0.76; 1.07), one-year all cause (HR: 1.09, 95% CI: 0.95; 1.25) and respiratory-related hospitalization (HR: 0.89, 95% CI: 0.72; 1.08). No significant differences were observed regarding total (€- 807, 95% CI: €- 2977; €1220) and respiratory-related (€- 1282, 95% CI: €- 3423; €534) costs. CONCLUSION: Our analyses suggest that the patient-related outcomes mortality, hospitalization, and costs do not differ between the two currently available antifibrotic drugs pirfenidone and nintedanib. Hence, the decision on treatment with pirfenidone versus treatment with nintedanib ought to be made case-by-case taking clinical characteristics, comorbidities, comedications, individual risk of side effects, and patients' preferences into account.

Mesenchymal Stromal Cell Secretome for Post-COVID-19 Pulmonary Fibrosis: A New Therapy to Treat the Long-Term Lung Sequelae?

To date, more than 100 million people worldwide have recovered from COVID-19. Unfortunately, although the virus is eradicated in such patients, fibrotic irreversible interstitial lung disease (pulmonary fibrosis, PF) is clinically evident. Given the vast numbers of individuals affected, it is urgent to design a strategy to prevent a second wave of late mortality associated with COVID-19 PF as a long-term consequence of such a devastating pandemic. Available antifibrotic therapies, namely nintedanib and pirfenidone, might have a role in attenuating profibrotic pathways in SARS-CoV-2 infection but are not economically sustainable by national health systems and have critical adverse effects. It is our opinion that the mesenchymal stem cell secretome could offer a new therapeutic approach in treating COVID-19 fibrotic lungs through its anti-inflammatory and antifibrotic factors.

Cost-effectiveness and budget impact of dolutegravir/lamivudine for treatment of human immunodeficiency virus (HIV-1) infection in the United States.

BACKGROUND: Dolutegravir(DTG)/lamivudine(3TC) is the first 2-drug regimen recommended as an initial treatment for people living with HIV (PLHIV). OBJECTIVE: To assess the cost-effectiveness and potential budget impact of DTG/3TC in the US healthcare setting. METHODS: A previously published hybrid decision-tree and Markov cohort state transition model was adapted to estimate the incremental costs and health outcome benefits over a patients' lifetime. DTG/3TC was compared with current standard of care in treatment naive and treatment experienced virologically suppressed PLHIV. Health states included in the model were based upon virologic response and CD4 cell count, with death as an absorbing state. Clinical data was informed by the Phase III GEMINI 1 and 2 clinical trials, a published network meta-analysis (NMA) in treatment-naive patients and the Phase III TANGO clinical trial in treatment experienced patients. Costs and utilities were informed by published data and discounted annually at a rate of 3%. A separate 5-year budget impact analysis was conducted assuming 5%-15% uptake in eligible treatment naive and 10%-30% uptake in eligible treatment experienced patients. RESULTS: In the treatment naive analyses based on GEMINI 1 and 2, DTG/3TC dominated, i.e., was less costly and more effective, than all comparators. DTG/3TC resulted in 0.083 incremental quality-adjusted life-years (QALYs) at a cost saving of $199,166 compared with the DTG + tenofovir disoproxil(TDF)/emtricitabine(FTC) comparator arm. The incremental QALY and cost savings for DTG/3TC compared with DTG/abacavir(ABC)/3TC, cobicistat-boosted darunavir(DRV/c)/tenofovir alafenamide(TAF)/FTC, and bictegravir (BIC)/TAF/FTC, based on NMA results were 0.465, 0.142, and 0.698, and $42,948, $122,846, and $44,962, respectively. In the analyses of treatment-experienced virologically suppressed patients based on TANGO, DTG/3TC offered slightly lower QALYs (-0.037) with an estimated savings of $78,730 when compared with continuation of TAF-based regimen (TBR). Sensitivity analyses demonstrated that these conclusions were relatively insensitive to alternative parameter estimates. The budget impact analysis estimated that by 5th year a total of 70,240 treatment naive patients and 1,340,480 treatment experienced patients could be eligible to be prescribed DTG/3TC. The estimated budget savings over 5 years ranged from $1.12b to $3.35b (corresponding to 27,512 to 82,536 on DTG/3TC by year 5) in the lowest and highest uptake scenarios, respectively. CONCLUSION: In conclusion, DTG/3TC with its comparable efficacy and lower drug acquisition costs, has the potential to offer significant cost savings to US healthcare payers for the initial treatment of treatment naive patients and as a treatment switching option for virologically suppressed patients. DISCLOSURES: This study was funded in full by ViiV healthcare, Brentford, UK. Medical writing to support this study was also funded in full by ViiV Healthcare, Brentford, UK. Butler, Hayward, and Jacob are employees of HEOR Ltd, the company performing this study funded by ViiV Healthcare. Anderson is an employee of GlaxoSmithKline and owns shares in the company. Punekar, Evitt, and Oglesby are employees of ViiV Healthcare and own stocks in GlaxoSmithKline.

The potential role of long-acting injectable cabotegravir-rilpivirine in the treatment of HIV in sub-Saharan Africa: a modelling analysis.

BACKGROUND: The use of a combination of the integrase inhibitor, cabotegravir, and the non-nucleoside reverse transcriptase inhibitor, rilpivirine, in a long-acting injectable form is being considered as an antiretroviral treatment option for people with HIV in sub-Saharan Africa. We aimed to model the effects of injectable cabotegravir-rilpivirine to help to inform its potential effectiveness and cost-effectiveness under different possible policies for its introduction. METHODS: We used an existing individual-based model of HIV to predict the effects of introducing monthly injections of cabotegravir-rilpivirine for people with HIV in low-income settings in sub-Saharan Africa. We evaluated policies in the context of 1000 setting scenarios that reflected characteristics of HIV epidemics and programmes in sub-Saharan Africa. We compared three policies for introduction of injectable cabotegravir-rilpivirine with continued use of dolutegravir-based oral regimens for: all individuals on antiretroviral therapy (ART); individuals with a recently measured viral load of more than 1000 copies per mL (signifying poor adherence to oral drugs, and often associated with drug resistance); and individuals with a recently measured viral load of less than 1000 copies per mL (a group with a lower prevalence of pre-existing drug resistance). We also did cost-effectiveness analysis, taking a health system perspective over a 10 year period, with 3% discounting of disability-adjusted life-years (DALYs) and costs. A cost-effectiveness threshold of US$500 per DALY averted was used to establish if a policy was cost-effective. FINDINGS: In our model, all policies involving the introduction of injectable cabotegravir-rilpivirine were predicted to lead to an increased proportion of people with HIV on ART, increased viral load suppression, and decreased AIDS-related mortality, with lesser benefits in people with a recently measured viral load of less than 1000 copies per mL. Its introduction is also predicted to lead to increases in resistance to integrase inhibitors and non-nucleoside reverse transcriptase inhibitors if introduced in all people with HIV on ART or in those with a recently measured viral load of less than 1000 copies per mL, but to a lesser extent if introduced in people with more than 1000 copies per mL due to concentration of its use in people less adherent to oral therapy. Consistent with the effect on AIDS-related mortality, all approaches to the introduction of injectable cabotegravir-rilpivirine are predicted to avert DALYs. Assuming a cost of $120 per person per year, use of this regimen in people with a recently measured viral load of more than 1000 copies per mL was borderline cost-effective (median cost per DALY averted across setting scenarios $404). The other approaches considered for its use are unlikely to be cost-effective unless the cost per year of injectable cabotegravir-rilpivirine is considerably reduced. INTERPRETATION: Our modelling suggests that injectable cabotegravir-rilpivirine offers potential benefits; however, to be a cost-effective option, its introduction might need to be carefully targeted to individuals with HIV who might otherwise have suboptimal adherence to ART. As data accumulate from trials and implementation studies, such findings can be incorporated into the model to better inform on the full consequences of policy alternatives. FUNDING: Bill & Melinda Gates Foundation, including through the HIV Modelling Consortium (OPP1191655).

Cost-effectiveness of the long-acting regimen cabotegravir plus rilpivirine for the treatment of HIV-1 and its potential impact on adherence and viral transmission: A modelling study.

INTRODUCTION: Combination antiretroviral therapy (cART) improves outcomes for people living with HIV (PLWH) but requires adherence to daily dosing. Suboptimal adherence results in reduced treatment effectiveness, increased costs, and greater risk of resistance and onwards transmission. Treatment with long-acting (LA), injection-based ART administered by healthcare professionals (directly observed therapy (DOT)) eliminates the need for adherence to daily dosing and may improve clinical outcomes. This study reports the cost-effectiveness of the cabotegravir plus rilpivirine LA regimen (CAB+RPV LA) and models the potential impact of LA DOT therapies. METHODS: Parameterisation was performed using pooled data from recent CAB+RPV LA Phase III trials. The analysis was conducted using a cohort-level hybrid decision-tree and state-transition model, with states defined by viral load and CD4 cell count. The efficacy of oral cART was adjusted to reflect adherence to daily regimens from published data. A Canadian health service perspective was adopted. RESULTS: CAB+RPV LA is predicted to be the dominant intervention when compared to oral cART, generating, per 1,000 patients treated, lifetime cost-savings of $1.5 million, QALY and life-year gains of 107 and 138 respectively with three new HIV cases averted. CONCLUSIONS: Economic evaluations of LA DOTs need to account for the impact of adherence and HIV transmission. This study adds to the existing literature by incorporating transmission and using clinical data from the first LA DOT regimen. Providing PLWH and healthcare providers with novel modes of ART administration, enhancing individualisation of treatment, may facilitate the achievement of UNAIDS 95-95-95 objectives.

Cost-utility analysis of apixaban compared with usual care for primary thromboprophylaxis in ambulatory patients with cancer.

BACKGROUND: Apixaban (2.5 mg) taken twice daily has been shown to substantially reduce the risk of venous thromboembolism (VTE) compared with placebo for the primary thromboprophylaxis of ambulatory patients with cancer who are starting chemotherapy and are at intermediate-to-high risk of VTE. We aimed to compare the health system costs and health benefits associated with primary thromboprophylaxis using apixaban with those associated with the current standard of care (where no primary thromboprophylaxis is given), from the perspective of Canada's publicly funded health care system in this subpopulation of patients with cancer over a lifetime horizon. METHODS: We performed a cost-utility analysis to estimate the incremental cost per quality-adjusted life-year (QALY) gained with primary thromboprophylaxis using apixaban. We obtained baseline event rates and the efficacy of apixaban from the Apixaban for the Prevention of Venous Thromboembolism in High-Risk Ambulatory Cancer Patients (AVERT) trial on apixaban prophylaxis. We estimated relative risk for bleeding, risk of complications associated with VTE treatment, mortality rates, costs and utilities from other published sources. RESULTS: Over a lifetime horizon, apixaban resulted in lower costs to the health system (Can$7902.98 v. Can$14 875.82) and an improvement in QALYs (9.089 v. 9.006). The key driver of cost-effectiveness results was the relative risk of VTE as a result of apixaban. Results from the probabilistic analysis showed that at a willingness to pay of Can$50 000 per QALY, the strategy with the highest probability of being most cost-effective was apixaban, with a probability of 99.87%. INTERPRETATION: We found that apixaban is a cost-saving option for the primary thromboprophylaxis of ambulatory patients with cancer who are starting chemotherapy and are at intermediate-to-high risk of VTE.

Cost-effectiveness analysis of apixaban compared to other direct oral anticoagulants for prevention of stroke in Austrian atrial fibrillation patients.

OBJECTIVES: Several direct oral anticoagulants (DOACs) have been approved by the European Medicines Agency since 2008. The aim of the present cost-effectiveness-analysis was to analyze apixaban compared to other DOACs and vitamin K antagonists (warfarin) in Austria. METHODS: A cost-utility-model was developed to simulate lifetime-costs and quality-adjusted-life-years of DOACs and warfarin, based on a published Markov-Model and 23 randomized trials with 94,656 atrial-fibrillation (AF) patients. Each year, a patient has a probability of suffering a clinically relevant (extracranial) bleed, an intracranial hemorrhage (ICH), an ischemic stroke or a myocardial infarction (MI), remaining healthy, or deceasing. Direct-costs (2018€) were derived from published sources from the payer's perspective. RESULTS: In the base-case, warfarin had the lowest cost of 12,968 € (95%-CI±593 €) followed by apixaban (15,269 €±661 €), edoxaban (15,534 €±641 €), dabigatran (15,687 €±667 €), and rivaroxaban (17,522 €±764 €). Apixaban had the highest quality-adjusted-life-years estimate at 5.45 (SD, 0.06). In a Monte-Carlo probabilistic sensitivity analysis, apixaban was cost-effective vs. edoxaban, dabigatran, warfarin, and rivaroxaban in 85.6%, 79.0%, 76.4%, and 61.2% of the simulations, respectively. CONCLUSION: In patients with AF and an increased risk of stroke, prophylaxis with apixaban was highly cost-effective from the perspective of the Austrian health-care system.

Non-warfarin oral anticoagulant copayments and adherence in atrial fibrillation: A population-based cohort study.

BACKGROUND: In patients with atrial fibrillation, incomplete adherence to anticoagulants increases risk of stroke. Non-warfarin oral anticoagulants (NOACs) are expensive; we evaluated whether higher copayments are associated with lower NOAC adherence. METHODS: Using a national claims database of commercially-insured patients, we performed a cohort study of patients with atrial fibrillation who newly initiated a NOAC from 2012 to 2018. Patients were stratified into low (<$35), medium ($35-$59), or high (≥$60) copayments and propensity-score weighted based on demographics, insurance characteristics, comorbidities, prior health care utilization, calendar year, and the NOAC received. Follow-up was 1 year, with censoring for switching to a different anticoagulant, undergoing an ablation procedure, disenrolling from the insurance plan, or death. The primary outcome was adherence, measured by proportion of days covered (PDC). Secondary outcomes included NOAC discontinuation (no refill for 30 days after the end of NOAC supply) and switching anticoagulants. We compared PDC using a Kruskal-Wallis test and rates of discontinuation and switching using Cox proportional hazards models. RESULTS: After weighting patients across the 3 copayment groups, the effective sample size was 17,558 patients, with balance across 50 clinical and demographic covariates (standardized differences <0.1). Mean age was 62 years, 29% of patients were female, and apixaban (43%), and rivaroxaban (38%) were the most common NOACs. Higher copayments were associated with lower adherence (P < .001), with a PDC of 0.82 (Interquartile range [IQR] 0.36-0.98) among those with high copayments, 0.85 (IQR 0.41-0.98) among those with medium copayments, and 0.88 (IQR 0.41-0.99) among those with low copayments. Compared to patients with low copayments, patients with high copayments had higher rates of discontinuation (hazard ratio [HR] 1.13, 95% confidence interval [CI] 1.08-1.19; P < .001). CONCLUSIONS: Among atrial fibrillation patients newly initiating NOACs, higher copayments in commercial insurance were associated with lower adherence and higher rates of discontinuation in the first year. Policies to lower or limit cost-sharing of important medications may lead to improved adherence and better outcomes among patients receiving NOACs.