Promising first-line immuno-combination therapies for unresectable hepatocellular carcinoma: A cost-effectiveness analysis.

BACKGROUND AND AIMS: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death all over the world, and brings a heavy social economic burden especially in China. Several immuno-combination therapies have shown promising efficacy in the first-line treatment of unresectable HCC and are widely used in clinical practice. Nevertheless, which combination is the most affordable one is unknown. Our study assessed the cost-effectiveness of the immuno-combinations as first-line treatment for patients with unresectable HCC from the perspective of Chinese payers. METHODS: A Markov model was built according to five multicenter, phase III, open-label, randomized trials (Himalaya, IMbrave150, ORIENT-32, CARES-310, LEAP-002) to investigate the cost-effectiveness of tremelimumab plus durvalumab (STRIDE), atezolizumab plus bevacizumab (A + B), sintilimab plus bevacizumab biosimilar (IBI305) (S + B), camrelizumab plus rivoceranib (C + R), and pembrolizumab plus lenvatinib (P + L). Three disease states were included: progression free survival (PFS), progressive disease (PD) as well as death. Medical costs were searched from West China Hospital, published literatures or the Red Book. Cost-effectiveness ratios (CERs) and incremental cost-effectiveness ratios (ICERs) were evaluated to compare costs among different combinations. Sensitivity analyses were performed to assess the robust of the model. RESULTS: The total cost and quality-adjusted life years (QALYs) of C + R, S + B, P + L, A + B and STRIDE were $12,109.27 and 0.91, $26,961.60 and 1.12, $55,382.53 and 0.83, $70,985.06 and 0.90, $84,589.01 and 0.73, respectively, resulting in the most cost-effective strategy of C + R with CER of $13,306.89 per QALY followed by S + B with CER of $24,072.86 per QALY. Compared with C + R, the ICER of S + B strategy was $70,725.38 per QALY, which would become the most cost-effective when the willing-to-pay threshold exceeded $73,500/QALY. In the subgroup analysis, with the application of Asia results in Leap-002 trial, the model results were the same as global data. In the sensitivity analysis, with the variation of parameters, the results were robust. CONCLUSION: As one of the promising immuno-combination therapies in the first-line systemic treatment of HCC, camrelizumab plus rivoceranib demonstrated the potential to be the most cost-effective strategy, which warranted further studies to best inform the real-world clinical practices.

Toripalimab plus chemotherapy in the treatment of metastatic triple-negative breast cancer: a cost-effectiveness analysis.

Objective: This study focuses on assessing the cost-effectiveness of incorporating toripalimab alongside chemotherapy for the treatment of patients diagnosed with metastatic triple-negative breast cancer from the perspective of the Chinese healthcare system. Methods: A partitioned survival model was constructed to simulate the costs and health outcomes over the lifetime of patients with mTNBC. Clinical data regarding overall survival, progression-free survival, and treatment-related adverse events were derived from the TORCHLIGHT clinical trials. Incremental cost-effectiveness ratio (ICER) were calculated based on the gains in quality-adjusted life-year (QALY). The willingness-to-pay (WTP) threshold was defined as $39,855.79 per QALY. Additionally, sensitivity analyses were conducted to examine the robustness of the model. Results: The total cost incurred by the group receiving toripalimab was $38,040.62, while the placebo plus chemotherapy was $26,102.07. The utilization of the toripalimab regimen resulted in an increase of 0.74 QALYs and an incremental cost of $11,938.55 compared to the placebo plus chemotherapy group. The ICER was $16,133.18/QALY, indicating that toripalimab plus chemotherapy is a cost-effective strategy according to the WTP threshold. Sensitivity analyses confirmed the robustness of the results. Conclusion: This study suggests that the addition of toripalimab to chemotherapy for the treatment of mTNBC is a cost-effective strategy. The findings provide valuable evidence to guide decision-making regarding treatment selection for patients with mTNBC in China.

Health and Economic Outcomes of Pembrolizumab in the Treatment of Metastatic Non-small Cell Lung Cancer (mNSCLC) and Melanoma in Italy.

BACKGROUND AND OBJECTIVE: In Italy, the management of metastatic non-small cell lung cancer and melanoma leads to significant healthcare challenges, necessitating cost-effective treatment strategies and offering valuable insights for healthcare policymakers and stakeholders. This study was designed to assess the costs, quality-adjusted life-years (QALYs) and disability-adjusted life-years (DALYs) associated with the health and economic outcomes of (1) pembrolizumab-combined chemotherapy administered as a first-line treatment for metastatic non-squamous and squamous non-small cell lung cancer (NSCLC) where the tumour presents with a programmed death-ligand 1 expression level < 50% and of (2) adjuvant pembrolizumab treatment for stage III melanoma. METHODS: Three cost-effectiveness models developed by MSD were investigated for each treatment indication. A unique model was built to assess the overall effect of pembrolizumab versus chemotherapy or watchful waiting in patients with lung cancer or melanoma, respectively. Theoretical cohorts of patients with metastatic squamous and non-squamous NSCLC were followed over time using a partitioned survival model with weekly cycles. A weekly cycle Markov model was employed for melanoma. The analysis was conducted from the Italian National Health Service perspective, considering a time horizon of 40 years (lifetime). A single closed cohort of treatable patients was followed over time for each indication (4000, 7000 and 900 for NSCLC squamous, non-squamous and melanoma, respectively). The costs evaluated included those for adverse drug events, non-drug disease management, subsequent treatment and terminal care. Drug acquisition and administration costs were excluded. RESULTS: For each treatment indication assessed, pembrolizumab produced downstream direct cost offsets (- €122,498,568, - €133,369,076 and - €32,993,242 for NSCLC squamous, non-squamous and melanoma indications, respectively), increased quality of life (+2088, +5317 and +2307 QALYs for NSCLC squamous, non-squamous and melanoma indications, respectively) and reduced disability (- 2658, - 7202 and - 3029 DALYs for NSCLC squamous, non-squamous and melanoma indications, respectively). Across indications, the total cost offsets of pembrolizumab were - €288,860,885, with 9712 QALYs gained and 12,889 DALYs avoided. CONCLUSIONS: The analysis demonstrated that, compared with chemotherapy, pembrolizumab is more cost effective in Italy as a first-line treatment in patients with metastatic squamous or non-squamous NSCLC and, if compared with watchful waiting, as adjuvant treatment in patients with stage III melanoma. The present analysis suggested that pembrolizumab use could lead to important health benefits for patients while offsetting a portion of cancer care costs.

Budget Impact of Disease-Modifying Treatments and a CRISPR Gene-Edited Therapy for Sickle Cell Disease.

BACKGROUND AND OBJECTIVE: Treatment of sickle cell disease (SCD) has traditionally focused on symptomatic and preventative care. Recent advances in novel therapeutic developments, likely to be orphan-designated, are anticipated to carry a substantial price tag. This study assesses the potential budget impact of adopting disease-modifying treatments, crizanlizumab and voxelotor, and pioneering CRISPR gene-edited therapy, CTX001, in the Belgian healthcare system. METHODS: The perspective of the Belgian healthcare payer (RIZIV-INAMI including patient copayments), a 5-year horizon with a 2-10% uptake of disease-modifying interventions, and a 2% uptake of CTX001 were considered. Data, encompassing target population, current (chronic and acute management, curative hematopoietic stem cell transplantation) and new (crizanlizumab, voxelotor, and CTX001) interventions, clinical effectiveness, adverse events, healthcare resource utilization, and associated costs, were gathered through a comprehensive literature review (first phase) and two Delphi panels involving hematologists (second phase). The cost difference between a "world with and without crizanlizumab, voxelotor, and CTX001" was calculated to obtain the budget impact. Three scenario analyses were conducted: a 5-13% and 4% uptake analysis, a 10-18% and 8% uptake analysis, respectively for disease-modifying treatments (crizanlizumab and voxelotor) and CTX001, and a 0% crizanlizumab uptake and managed entry agreements analysis . A ± 20% univariate sensitivity analysis was performed to test the robustness of the analysis. RESULTS: The total five-year cumulative budget impact was estimated at €30,024,968, with 91% attributed to drug acquisition costs. The largest budget impact share was for CTX001 (€25,575,150), while crizanlizumab (€2,301,095) and voxelotor (€2,148,723) was relatively small. In scenarios one and three, a two-fold increase of the cumulative budget impact to €60,731,772 and a four-fold increase to €120,846,256 from the base case was observed. In scenario three, this budget impact decreased by 63% to €11,212,766. Patient population size, number of treated patients, and drug costs influenced the analysis the most, while discontinuation, acute crisis, and adverse event rates had comparatively minimal impact. CONCLUSIONS: Belgian decision-makers may consider alternative financing models, such as outcome-based risk-sharing agreements or annuities, to ensure sustainable coverage of these treatments. This study adheres to recommended practices for assessing budget impact of orphan drugs, distinguishing it from earlier studies with potentially weaker methodologies.

Sequential interleukin-17 inhibitors for moderate-to-severe plaque psoriasis who have an IL-17 inhibitors failure in a resource limited country: An economic evaluation.

BACKGROUND: Biologics has been known to be effective for patients with psoriasis. However, optimal treatment pathways and their cost-effectiveness are limited in a resource-limited country. This study assessed the cost-effectiveness of different sequential biologics for moderate-to-severe plaque psoriasis. METHOD: A hybrid model from a societal perspective was used. Model inputs were derived from network meta-analysis, clinical trials, and published literature. Three different sequential biologic treatments were assessed; Sequence 1; 1st Interleukin-17 (IL-17) inhibitor (secukinumab) followed by 2nd IL-17 inhibitors (ixekizumab or brodalumab), then 3rd IL-23 inhibitor (guselkumab), Sequence 2; ixekizumab followed by secukinumab or brodalumab, then guselkumab, and Sequence 3; brodalumab followed by ixekizumab or secukinumab, then guselkumab. Methotrexate or ciclosporin was used as standard of care (SoC). RESULTS: All three different sequential biologic therapies could gain total quality-adjusted life year (QALY), but they had higher cost than SoC. Sequence 1 had the lowest incremental cost-effectiveness ratio (ICER) compared to SoC at 621,373 THB/QALY (19,449 $/QALY). ICER for Sequence 2 was 957,258 THB/QALY (29,962 $/QALY), while that for Sequence 3 was 1,332,262 THB/QALY (41,700 $/QALY). Fully incremental analysis indicated that Sequence 3 was dominated by Sequence 1 and Sequence 2. ICER for Sequence 2 was 7,206,104 THB/QALY (225,551 $/QALY) when compared to Sequence 1. CONCLUSION: At the current willingness-to-pay of 160,000 THB/QALY, no sequential IL-17 inhibitor was cost-effective compared to SoC. Secukinumab followed by ixekizumab or brodalumab then guselkumab (Sequence 1) may be the most appropriate option compared with other treatments.

Health care resource utilization and direct costs incurred over 24 months after initiating galcanezumab or standard-of-care preventive migraine treatments in the United States.

BACKGROUND: Health care resource utilization (HCRU) and direct costs incurred over 12 months following initiation of galcanezumab (GMB) or standard-of-care (SOC) preventive migraine treatments have been evaluated. However, a gap in knowledge exists in understanding longer-term HCRU and direct costs. OBJECTIVE: To compare all-cause and migraine-related HCRU and direct costs in patients with migraine initiating GMB or SOC preventive migraine treatments over a 24-month follow-up. METHODS: This retrospective study used Optum deidentified Market Clarity Data. The study included adults diagnosed with migraine, with at least 1 claim for GMB or SOC preventive migraine therapy (September 2018 to March 2020), with continuous enrollment for 12 months before and 24 months after (follow-up) the index date (date of first GMB or SOC claim). Propensity score (PS) matching (1:1) was used to balance cohorts. All-cause and migraine-related HCRU and direct costs for GMB vs SOC cohorts were reported as mean (SD) per patient per year (PPPY) over a 24-month follow-up and compared using a Z-test. Costs were inflated to 2022 US$. RESULTS: After PS matching, 2,307 patient pairs (mean age: 44.4 years; female sex: 87.3%) were identified. Compared with the SOC cohort, the GMB cohort had lower mean (SD) PPPY all-cause office visits (17.9 [17.7] vs 19.1 [18.7]; P = 0.023) and migraine-related office visits (2.6 [3.3] vs 3.0 [4.7]; P = 0.002) at follow-up. No significant differences were observed between cohorts in other all-cause and migraine-related events assessed including outpatient visits, emergency department (ED) visits, inpatient stays, and other medical visits. The mean (SD) costs PPPY were lower in the GMB cohort compared with the SOC cohort for all-cause office visits ($4,321 [7,518] vs $5,033 [7,211]; P < 0.001) at follow-up. However, the GMB cohort had higher mean (SD) PPPY all-cause total costs ($24,704 [30,705] vs $21,902 [28,213]; P = 0.001) and pharmacy costs ($9,507 [12,659] vs $5,623 [12,605]; P < 0.001) compared with the SOC cohort. Mean (SD) costs PPPY were lower in the GMB cohort for migraine-related office visits ($806 [1,690] vs $1,353 [2,805]; P < 0.001) compared with the SOC cohort. However, the GMB cohort had higher mean (SD) PPPY migraine-related total costs ($8,248 [11,486] vs $5,047 [9,749]; P < 0.001) and migraine-related pharmacy costs ($5,394 [3,986] vs $1,761 [4,133]; P < 0.001) compared with the SOC cohort. There were no significant differences between cohorts in all-cause and migraine-related costs for outpatient visits, ED visits, inpatient stays, and other medical visits. CONCLUSIONS: Although total costs were greater for GMB vs SOC following initiation, changes in a few categories of all-cause and migraine-related HCRU and direct costs were lower for GMB over a 24-month follow-up. Additional analysis evaluating indirect health care costs may offer insights into further cost savings incurred with preventive migraine treatment.

Cost-effectiveness analysis of the tislelizumab versus docetaxel for advanced or metastatic non-small-cell lung cancer in China.

Background: Tislelizumab is the first PD-1 inhibitor in China to demonstrate superior efficacy in second-line or third-line treatment of patients with advanced or metastatic non-small-cell lung cancer (NSCLC). This study aimed to evaluate the cost-effectiveness of tislelizumab compared to docetaxel from a Chinese healthcare system perspective. Methods: A dynamic Markov model was developed to evaluate the cost-effectiveness of tislelizumab in comparison to docetaxel in second or third-line treatment. The efficacy data utilized in the model were derived from the RATIONALE-303 clinical trial, while cost and utility values were obtained from the drug data service platform and published studies. The primary outcomes of the model encompassed quality-adjusted life years (QALYs), costs, and incremental cost-effectiveness ratios (ICERs). One-way sensitivity analysis and probabilistic sensitivity analysis were conducted to validate the robustness of the base case analysis results. Results: The tislelizumab group demonstrated a cost increase of CNY 117,473 and a gain of 0.58 QALYs compared to the docetaxel group, resulting in an ICER value of CNY 202,927 per QALY gained. Conclusion: The administration of tislelizumab in patients with advanced or metastatic NSCLC not only extends the progression-free survival (PFS) and overall survival (OS). Moreover, this treatment demonstrates a favorable cost-effectiveness profile across the Chinese population.

Italian healthcare resource consumptions and direct costs of adults with atopic dermatitis before and after dupilumab treatment.

BACKGROUND: Atopic dermatitis (AD) is a heterogeneous disease, associated with comorbidities, and high healthcare consumptions and costs. This study assessed the burden before and after treatment with dupilumab in adults with severe AD from 2018 to 2020, from the perspective of the Italian National Health Service (SSN). METHODS: From Fondazione Ricerca e Salute's administrative healthcare database (~5 million inhabitants/year), adults treated with dupilumab from 09/01/2018 to 31/12/2020 (index date) and a five-year lookback were identified. Age, sex and comorbidities at baseline, concomitant drugs, overnight hospitalizations, outpatient specialist services and direct costs charged to the SSN one year before/after index date were assessed. RESULTS: Of 337 adults treated with dupilumab (5.8x100,000 adult inhabitants/2019; 8.0x100,000/2020; 55% males; mean age 43±19), 68% (228/337) had ≥12-month follow-up available. Asthma was a common comorbidity (23% patients). Rates of patients treated with nearly all concomitant AD-related therapies reduced from 12 months before to 12 months after dupilumab treatment: antibacterials (from 59% to 50%), systemic corticosteroids (55% to 29%), antihistamines (54% to 38%) and cyclosporine (52% to 7%). A similar trend was observed among patients with asthma as comorbidity. Within 12 months before/after dupilumab, patients hospitalized halved from 14% to 7%, and patients receiving outpatient specialist care reduced from 72% to 65%. Annual mean direct total costs per patient treated with dupilumab charged to the SSN, net of dupilumab cost, were €1384 and €773, before and after dupilumab dispensation, respectively. CONCLUSIONS: Before dupilumab, observed patients had higher healthcare resource consumptions and direct SSN costs than after dupilumab.

Modelling the opportunity for cost-savings or patient access with biosimilar adalimumab and tocilizumab: a European perspective.

OBJECTIVES: Biosimilars improve patient access by providing cost-effective treatment options. This study assessed the potential for savings and expanded patient access with increased use of two biosimilar disease modifying anti-rheumatic drugs (DMARDs): (a) approved adalimumab biosimilars and (b) the first tocilizumab biosimilar, representing an established biosimilar field and a recent biosimilar entrant in France, Germany, Italy, Spain, and the United Kingdom (UK). METHODS: Separate ex-ante analyses were conducted for each country, parameterized using country-specific list prices, unit volumes annually, and market shares for each therapy. Discounting scenarios of 10%, 20%, and 30% were tested for tocilizumab. Outputs included direct cost-savings associated with drug acquisition or the incremental number of patients that could be treated if savings were redirected. Two biosimilar conversion scenarios were tested. RESULTS: Savings associated with a 100% conversion to adalimumab biosimilar ranged from €10.5 to €187 million (UK and Germany, respectively), or an additional 1,096 to 19,454 patients that could be treated using the cost-savings. Introduction of a tocilizumab biosimilar provided savings up to €29.3 million in the most conservative scenario. Exclusive use of tocilizumab biosimilars (at a 30% discount) could increase savings to €28.8 to €113 million or expand access to an additional 43% of existing tocilizumab users across countries. CONCLUSION: This study demonstrates the benefits that can be realized through increased biosimilar adoption, not only in an untapped tocilizumab market, but also through incremental increases in well-established markets such as adalimumab. As healthcare budgets continue to face downwards pressure globally, strategies to increase biosimilar market share could prove useful to help manage financial constraints.

Assay-guided treatment sequencing in chronic lymphocytic leukemia (CLL): a cost-effectiveness analysis.

Costly targeted cancer treatments challenge publicly-funded healthcare systems seeking to align expected benefit with value for money. In 2021, The Canadian Agency for Drugs and Technologies in Health (CADTH) published a provisional funding algorithm for risk-based treatment of chronic lymphocytic leukemia (CLL). We estimate the cost-effectiveness of this algorithm against current standard of care. We constructed a probabilistic Markov model comparing next generation sequencing (NGS) assay-guided front-line treatment of acalabrutinib versus venetoclax with obinutuzumab to a comparator wherein patients initiate acalabrutinib. The primary outcome was the incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained. Analyses were conducted from the British Columbia healthcare system perspective, with outcomes discounted at 1.5%. Assay informed treatment for patients with CLL resulted in an incremental cost effectiveness ratio of $18,040 (95% CI $16,491-$19,501) per quality adjusted life-year (QALY) gained. The probability of the NGS guided treatment algorithm being cost effective was 80% at a willingness to pay threshold of $50,000 and a corresponding ICER of $18,040. Assay-guided treatment sequencing adds additional costs to healthcare but may be a cost-effective intervention for adult patients with CLL. Integration of real-world evidence would improve the validity and reliability of model estimated for decision-makers.

Cost­effectiveness analysis of tislelizumab plus chemotherapy in Chinese patients with advanced or metastatic oesophageal squamous cell carcinoma.

The RATIONALE-306 study revealed that patients with advanced or metastatic oesophageal squamous cell carcinoma (OSCC) could benefit from treatment with tislelizumab plus chemotherapy. This study aimed to evaluate the cost-effectiveness of tislelizumab plus chemotherapy for treating OSCC from the perspective of the Chinese healthcare system. Partitioned survival model estimated the cost-effectiveness of tislelizumab plus chemotherapy compared with chemotherapy alone for treating OSCC using RATIONALE-306 data. Costs and utilities were obtained from local databases and published studies. Costs, quality-adjusted life-years (QALYs), life-years, incremental cost-effectiveness ratios (ICER), incremental net health benefits (INHB), and incremental net monetary benefits (INMB) were outcomes. Price simulation were conducted at the willingness-to-pay (WTP) threshold. Sensitivity and subgroup analyses were performed to assess model robustness. Compared with chemotherapy alone, tislelizumab plus chemotherapy yielded an ICER of USD 27,896/QALY, gained an additional 0.414 QALYs and 0.751 life-years, and increased the cost by USD 11,560. Probabilistic sensitivity analysis revealed that tislelizumab plus chemotherapy was cost-effective at the WTP of USD 38,258/QALY with probability of 94.43%. When the price in China was less than USD 3.714 per mg, the price simulation results indicated that tislelizumab plus chemotherapy was cost-effective at a WTP threshold of USD 38,258. Tislelizumab plus chemotherapy yielded an INHB of 0.112 QALYs and an INMB of USD 4,279 compared with chemotherapy alone at a WTP threshold of USD 38,258. Based on the sensitivity analyses, the above results were stable. A general trend was observed for subgroups with better survival benefits related to a higher probability of cost-effectiveness. From the Chinese healthcare perspective, tislelizumab plus chemotherapy is more cost-effective than chemotherapy alone as a first-line therapy for OSCC. These findings can help clinicians make optimal clinical decisions and assist decision-makers in evaluating the cost-effectiveness of tislelizumab in clinical practice.

Budget impact analysis of biosimilar natalizumab in the US.

OBJECTIVES: Biosimilars provide an opportunity for a more sustainable and cost-effective treatment for multiple sclerosis (MS). This study evaluated the potential financial impact of implementing a formulary change from reference to biosimilar natalizumab (NTZ) from the US commercial payer perspective. STUDY DESIGN: The budget impact of transitioning to biosimilar NTZ for the treatment of relapsing-remitting MS (RRMS) was estimated over a 3-year time horizon based on real-world dosing. Additional scenario analyses were conducted by varying the price differential of biosimilar NTZ. METHODS: The target population was estimated from a 1-million-member hypothetical commercial health plan. Model inputs were drug acquisition costs and treatment-related and patient coinsurance costs. Budget impact and cost savings per member per year were calculated by assuming a biosimilar uptake of 10% in year 1 to 20% in year 3. RESULTS: Over 3 years, 255 patients were estimated to be treated with high-efficacy disease-modifying therapies for RRMS. The inclusion of biosimilar NTZ onto a formulary would result in cumulative cost savings to payers of $452,611 over 3 years, with mean savings per treated member per year of $1179, $1769, and $2359 in years 1, 2, and 3, respectively. One-way sensitivity analyses indicated that budget impact results were most sensitive to drug acquisition costs of both reference and biosimilar NTZ. CONCLUSION: Adoption of biosimilar NTZ can yield considerable cost savings to US health plans that could result in increased treatment access for patients with RRMS.

Cost-efficiency and budget-neutral expanded access modeling of pembrolizumab versus the novel PD-1 inhibitor toripalimab in locally advanced or metastatic nonsquamous non-small cell lung cancer.

AIMS: To estimate in a panel of patients with locally advanced/metastatic nonsquamous non-small cell lung cancer (NSCLC) treated with a programmed death receptor-1 inhibitor in the US in 2024 (1) the cost-efficiency of toripalimab regimens compared to pembrolizumab regimens; and (2) the budget-neutral expanded access to additional toripalimab cycles and regimens from accrued savings. METHODS: Simulation modeling of toripalimab + pemetrexed + carboplatin in nonsquamous NSCLC to a similar pembrolizumab regimen in a panel of 49,647 patients; utilizing two cost inputs (wholesale acquisition cost (WAC) at market entry and an estimated ex ante toripalimab price point of 80% of pembrolizumab average sales price (ASP)) plus administration costs over one and two years of treatment with treatment rates from 1%-10%. Scenario analyses with treatment durations equivalent to toripalimab and pembrolizumab trials' median PFS were also conducted. RESULTS: In the WAC-based models, toripalimab saves $2,223 per patient per cycle and $40,014 over 1 year of treatment ($77,805 over 2 years). Extrapolated to the 49,647-patient panel, estimated 1-year savings range from $19,865,840 (1% treatment rate) to $198,658,399 (10% rate). Reallocating these savings permits budget-neutral expanded access to an additional 1,753 (1% rate) to 17,533 (10% rate) toripalimab maintenance cycles or to an additional 97 (1% rate) to 972 (10%) full 1-year toripalimab regimens with all agents. Two-year savings range from $38,628,022 (1% rate) to $386,280,221 (10%). Reallocating these efficiencies provides expanded access ranging from 3,409 (1% rate) to 34,093 (10%) additional toripalimab cycles or to 97 to 973 full 2-year regimens. The ex ante ASP model showed similar results as did the scenario analyses but at a lower magnitude than the base case. CONCLUSION: Toripalimab generates significant savings that enable budget-neutral funding for up to 17,533 [34,093] additional maintenance cycles over one year [two years] with toripalimab + pemetrexed in nonsquamous NSCLC, or 972 [973] full one-year [two-year] regimens.

An estimated 49,647 patients with advanced or metastatic nonsquamous non-small cell lung cancer (NSCLC) will be treated with a PD-1 inhibitor in the US in 2024. Toripalimab, a PD-1 inhibitor recently approved by the US Food and Drug Administration for the treatment of nasopharyngeal carcinoma, has also been found to be beneficial in patients with nonsquamous NSCLC when used in combination with chemotherapy. We conducted an economic simulation of the costs of toripalimab + pemetrexed + carboplatin versus the costs of a similar regimen with the PD-1 inhibitor pembrolizumab in the treatment of patients with nonsquamous NSCLC. Our simulation models used two US cost inputs for toripalimab: the wholesale acquisition cost or "list price" at market entry and, as no average sales price (ASP) will be available for toripalimab for several quarters, a hypothetical toripalimab price point of 80% of the pembrolizumab ASP. We compared the savings in each scenario when between 1% and 10% of the 49,647 nonsquamous NSCLC patients are treated with the toripalimab regimen. We then evaluated how these savings could be re-allocated, without requiring extra funding, to provide more patients with access to toripalimab treatment on a budget-neutral basis. We found that, if 1% of new cases of advanced/metastatic nonsquamous NSCLC were treated with toripalimab for 1 year, these savings are enough to purchase up to 1,753 additional toripalimab maintenance cycles; or these savings could provide up to an additional 97 patients with full one-year regimens with all agents (toripalimab + chemotherapy). If 10% of new cases were treated with toripalimab for 1 year, the savings are enough to purchase up to 17,533 additional toripalimab maintenance cycles; or these savings could provide up to an additional 972 patients with full one-year regimens with all agents.

Health Care Resource Use for Modern First-Line Treatments in Metastatic Renal Cell Carcinoma.

Importance: Immuno-oncology agents have changed the treatment paradigm for metastatic renal cell carcinoma (mRCC). Such therapies improve survival but can impose considerable health care resource use (HCRU) and associated costs, necessitating their examination. Objective: To compare HCRU, costs, and clinical outcomes among patients receiving first-line pembrolizumab plus axitinib (P+A) or ipilimumab plus nivolumab (I+N). Design, Setting, and Participants: This retrospective cohort study used data from an administrative claims database on patients with mRCC receiving first-line P+A or I+N that was initiated between January 2018 and May 2020. Data were analyzed from February 2021 to July 2022. Exposure: First-line P+A or I+N. Main Outcome and Measures: HCRU and costs during the first 90 days, full first-line treatment, and full follow-up periods were assessed. Using Kaplan-Meier analysis, time on treatment, overall survival, time to first emergency department (ED) visit, and time to first inpatient stay were compared. Results: Among 507 patients, there were 126 patients receiving P+A (91 male [72.2%]; mean [SD] age, 67.93 [9.66] y) and 381 patients receiving I+N (271 male [71.1%]; mean [SD] age, 66.52 [9.94] years). The median time on treatment was longer for the P+A compared with I+N group (12.4 months [95% CI, 8.40 months to not estimable] vs 4.1 months [95% CI, 3.07 to 5.30 months]; P < .001). The median time to first ED visit was longer for the P+A than I+N group (7.2 months [95% CI 3.9 to 11.1 months ] vs 3.3 months [95% CI, 2.6 to 3.9 months]; P = .005), as was time to first inpatient stay (9.0 months [95% CI 6.5 months to not estimable] vs 5.6 months [95% CI, 3.9 to 7.9 months]; P = .02). During the first 90 days, a lower proportion of the P+A than N+I group had ED visits (43 patients [34.1%] vs 182 patients [47.8%] and inpatient stays (24 patients [19.1%) vs144 patients [37.8%]; P < .001). During full follow-up, mean total adjusted costs were similar for P+A and I+N groups, but adjusted 12-month estimated total costs were higher for P+A than I+N groups ($325 574 vs $ 263 803; P = .03). Conclusions and Relevance: In this study, treatment with P+A was associated with longer time on treatment, time to first ED visit, and inpatient stay, while 12-month estimated costs were higher for the P+A group. This is among the first clinical studies to evaluate economic burden associated with modern treatments for mRCC.

Tocilizumab use in giant cell arteritis: comparing Pharmaceutical Benefits Scheme eligible and ineligible cases in South Australia.

Tocilizumab (TCZ) is increasingly used as a steroid-sparing agent in giant cell arteritis (GCA), but there are strict Pharmaceutical Benefits Scheme (PBS) restrictions for its use in Australia. Patients who do not meet the PBS criteria can obtain TCZ through public hospital individual patient use (IPU) schemes which may not be universally accessible. We compared patients receiving IPU-approved TCZ with patients receiving PBS-subsidised TCZ and found IPU approvals were granted mainly for visual loss, a serious complication of GCA, in patients who otherwise failed to meet PBS criteria. Further studies demonstrating that TCZ is comparatively more effective than prednisolone monotherapy, as well as cost-effective, are needed to substantiate the rationale for expanding PBS approval criteria.

Geographic and economic influences on benralizumab prescribing for severe asthma in Japan.

Benralizumab, a monoclonal antibody targeting IL-5 receptors, reduces exacerbations and oral corticosteroid requirements for severe, uncontrolled eosinophilic asthma. In Japan, geographic disparities in asthma outcomes suggest differential prescribing and access. This study aimed to quantify regional prescribing variations for benralizumab nationwide. Using Japan's National Database (NDB) of insurance claims (2009-2019), benralizumab standardized claim ratios (SCRs) were calculated for 47 prefectures. Correlations between SCRs and other biologics' SCRs, economic variables like average income, and physician densities were evaluated through univariate analysis and multivariate regressions. Income-related barriers to optimal prescribing were examined. Wide variation emerged in benralizumab SCRs, from 40.1 to 184.2 across prefectures. SCRs strongly correlated with omalizumab (r = 0.61, p < 0.00001) and mepolizumab (r = 0.43, p = 0.0024). Average monthly income also positively correlated with benralizumab SCRs (r = 0.45, p = 0.0016), whereas lifestyle factors were insignificant. Respiratory specialist density modestly correlated with SCRs (r = 0.29, p = 0.047). In multivariate regressions, average income remained the most robust predictor (B = 0.74, p = 0.022). Benralizumab SCRs strongly associate with income metrics more than healthcare infrastructure/population factors. Many regions show low SCRs, constituting apparent prescribing gaps. Access barriers for advanced asthma therapies remain inequitable among Japan's income strata. Addressing affordability alongside specialist allocation can achieve better prescribing quality and asthma outcomes.

Cost-effectiveness of RSVpreF vaccine and nirsevimab for the prevention of respiratory syncytial virus disease in Canadian infants.

BACKGROUND: Health Canada recently authorized the RSVpreF pregnancy vaccine and nirsevimab to protect infants against respiratory syncytial virus (RSV) disease. OBJECTIVE: Assess the cost-effectiveness of RSVpreF and nirsevimab programs in preventing RSV disease in infants, compared to a palivizumab program. METHODS: We used a static cohort model of a Canadian birth cohort during their first RSV season to estimate sequential incremental cost-effectiveness ratios (ICERs) in 2023 Canadian dollars per quality-adjusted life year (QALY) for nine strategies implemented over a one-year time period, from the health system and societal perspectives. Sensitivity and scenario analyses were conducted to explore the impact of uncertainties on the results. RESULTS: All-infants nirsevimab programs averted more RSV-related outcomes than year-round RSVpreF programs, with the most RSV cases averted in a seasonal nirsevimab program with catch-up. Assuming list prices for these immunizing agents, all-infants nirsevimab and year-round RSVpreF programs were never cost-effective, with ICERs far exceeding commonly used cost-effectiveness thresholds. Seasonal nirsevimab with catch-up for infants born outside the RSV season was a cost-effective program if prioritized for infants at moderate/high-risk (ICER <$28,000 per QALY) or those living in settings with higher RSV burden and healthcare costs, such as remote communities where transport would be complex (ICER of $5700 per QALY). Using a $50,000 per QALY threshold, an all-infants nirsevimab program could be optimal if nirsevimab is priced at <$110-190 per dose. A year-round RSVpreF for all pregnant women and pregnant people plus nirsevimab for infants at high-risk was optimal if nirsevimab is priced at >$110-190 per dose and RSVpreF priced at <$60-125 per dose. INTERPRETATION: Prophylactic interventions can substantially reduce RSV disease in infants, and more focused nirsevimab programs are the most cost-effective option at current product prices.

Cost-utility and budget impact analysis of neoadjuvant dual HER2 targeted therapy for HER2-positive breast cancer in Sri Lanka.

This study aimed to assess the cost-utility and budget impact of dual to single HER2 targeted neoadjuvant therapy for HER2-positive breast cancer in Sri Lanka. A five-health state Markov model with lifetime horizon was used to assess the cost-utility of neoadjuvant trastuzumab (T) plus pertuzumab (P) or lapatinib (L) compared to single therapy of T with chemotherapy (C), in public healthcare system and societal perspectives. Input parameters were estimated using local data, network meta-analysis, published reports and literature. Costs were adjusted to year 2021 (1USD = LKR194.78). Five-year budget impact for public healthcare system was assessed. Incremental cost-effectiveness ratios in societal perspective for neoadjuvantLTC plus adjuvantT (strategy 3), neoadjuvantPTC plus adjuvantT (strategy 2), neoadjuvantLTC plus adjuvantLT (strategy 5), and neoadjuvantPTC plus adjuvantPT (strategy 4) compared to neoadjuvantTC plus adjuvantT (strategy 1) were USD2716, USD5600, USD6878, and USD12127 per QALY gained, respectively. One GDP per-capita (USD3815) was considered as the cost-effectiveness threshold for the analysis. Even though only the ICER for strategy 3 was cost-effective, uncertainty of efficacy parameter was revealed. For strategy 2 neoadjuvant PTC plus adjuvant T, a 25% reduction of neoadjuvant regimen cost was required to be cost effective for use in early HER2 positive breast cancer.

Budget impact analysis of the novel PD-1 inhibitor toripalimab versus pembrolizumab in recurrent or metastatic nasopharyngeal carcinoma.

AIM: To estimate the budget impact of adding a toripalimab regimen as a treatment option to the existing pembrolizumab regimen, both including gemcitabine and cisplatin, in untreated recurrent/metastatic nasopharyngeal carcinoma (R/M NPC) using the published wholesale acquisition cost (WAC) and average sales price (ASP). METHODS: Budget impact analysis comparing a treatment mix "without" versus "with" the toripalimab regimen in the US eligible annual incident R/M NPC population, a 3-year time horizon, toripalimab/pembrolizumab market splits of 60/40 (Y1) and 80/20 (Y2/3), and medication adjustments for discontinuation or progression. Cost inputs included drugs, administration, and adverse event (AE) management. The models were replicated for a hypothetical 1-million-member health plan in which costs per-member-per-month (PMPM) and per-member-per-year (PMPY) were estimated. One-way (OWSA) and probabilistic sensitivity analyses (PSA) as well as scenario analyses were performed. RESULTS: In the "without" scenario, the 3-year WAC-based costs for the pembrolizumab regimen total $1,449,695,333 ($1,305,632,448 for treatment and $144,062,885 for managing AEs). In the "with" scenario, total 3-year costs for pembrolizumab decline to $380,012,135 with toripalimab adding $885,505,900 ($779,206,567 for treatment and $106,299,333 for AE management). Annual net savings range from $46,526,152 in 2024 to $71,194,214 in 2026, for 3-year savings of $184,177,298. Associated net savings in a 1-million-member health plan are $543,068 over 3 years with savings of $0.045 PMPM and $0.543 PMPY. The ASP-based model shows similar patterns with 3-year net savings of $174,235,983 in the US incident population and savings of $0.043 PMPM and $0.514 PMPY in a 1-million-member health plan. The PSA support base case findings; OWSA and scenario analyses reveal how parameter variability impacts results. CONCLUSION: Savings between $174 million and $184 million can be achieved from treating 60% of R/M NPC patients in year 1 and 80% in years 2 and 3 with the toripalimab regimen over a similar pembrolizumab regimen.

Toripalimab, a human monoclonal anti-body that targets PD-1, was recently approved by the US Food and Drug Administration (FDA) for the first-line treatment of adults with metastatic or recurrent, locally advanced nasopharyngeal carcinoma (NPC), in combination with gemcitabine and cisplatin. We evaluated how much it would cost a payor to cover the FDA-approved toripalimab plus gemcitabine and cisplatin regimen (the toripalimab regimen) to a non-FDA-approved pembrolizumab plus gemcitabine and cisplatin regimen (the pembrolizumab regimen). With no trial data available for such pembrolizumab regimen, we assumed that it would be comparable to the toripalimab regimen in efficacy and safety. Our model adopted a 3-year time horizon and assumed a 60/40 market share split in year 1 and an 80/20 market split in years 2 and 3. It included two US cost inputs: the wholesale acquisition cost (WAC) or "list price" at market entry and, as no average sales price (ASP) will be available for toripalimab for several quarters, a toripalimab price point of 80% of the pembrolizumab ASP. We adjusted for patients whose cancer progressed or who discontinued treatment to determine the number of fully-treated-patient-equivalents. We found that treating 60% of NPC patients in year 1 and 80% in years 2 and 3 with the toripalimab regimen instead of the pembrolizumab regimen generates, for the entire adjusted patient population, savings ranging from $174 million when using ASP to $184 million when using WAC.