An evaluation of the utilisation of biosimilar monoclonal antibody drugs in Ireland and barriers to their usage.

BACKGROUND: While biologic drugs have demonstrated efficacy across a range of indications, patient access to these drugs is constrained due to their high cost. Biosimilars provide a means to increase patient access while reducing the financial burden. AIMS: The primary objective was to determine the current usage of biosimilar and reference trastuzumab and rituximab in four Irish hospitals. A secondary objective involved determining barriers to biosimilar usage. METHODS: This project involved a retrospective chart review to analyse the usage of reference and biosimilar versions of trastuzumab and rituximab. Additionally, a prospective cross-sectional study identified barriers to the usage of biosimilars via the distribution of a novel questionnaire to patients, pharmacists, doctors and students. RESULTS: The utilisation of biosimilar intravenous trastuzumab and rituximab ranged from 39 to 100%, and 0 to 89%, respectively. A total of n = 479 questionnaire responses were included. Biosimilar awareness was significantly lower among 'Doctors and Medical Students' (45.3%; 95% [CI, 33.8-57.3%]) compared to 'Pharmacists and Pharmacy Students' (97.1%; 95% [CI, 94-98.8%; comparison p < 0.001]). A significant majority of healthcare professionals agreed biosimilars should have consistent nomenclature (p < 0.001). A significant majority of patients (87.3%, 95% [CI, 81.3-92%; p < 0.001]) indicated that they would agree to commence using a biosimilar medicine. CONCLUSION: Biosimilar versions of trastuzumab and rituximab were in use to a variable extent. There remains a considerable opportunity to further increase the usage to maximise their potential benefits. A series of challenges were identified including reduced awareness among the medical profession and lack of clear nomenclature.

Budget impact analysis of daratumumab for light-chain amyloidosis in Cyprus.

OBJECTIVE: The aim of this study is to assess the budget impact of daratumumab for light-chain amyloidosis in Cyprus. METHODS: A budget impact model assessed the cost prior and after the introduction of daratumumab for light-chain amyloidosis. All related costs were set from the perspective of Cyprus NHS. Clinical data were extracted from the published trials. One-way sensitivity analysis was conducted. We reported incremental budget impact, per member per month, per year, and per treated member per month. RESULTS: The introduction of D-VCd led to a net budget impact of €254,264 in the first year, which escalated to €497,007 by fifth year. The PMPY was estimated at €0.2893 in the first year, reaching €0.5246 at fifth year, the PMPM were at €0.0241 at the first year escalating to €0.0437 at the fifth year, and the PTMPM costs were €2,379 at the first year and gauged to €4,435 by fifth year. Our results were sensitive to incidence of the disease, percentage of patients without cardiac involvement and daratumumab cost. CONCLUSIONS: The introduction of daratumumab for AL amyloidosis, with a 90% annual uptake over 5 years, leads to a substantial budget impact. Managed entry agreement schemes can be considered in order to mitigate the impact.

Daratumumab utilization and cost analysis among patients with multiple myeloma in a US community oncology setting.

Background: The introduction of daratumumab into the treatment of multiple myeloma has improved outcomes in patients; however, community oncologists often dose more frequently than the US FDA-approved label. Materials and methods: Integra analyzed its database to elucidate daratumumab treatment patterns and the impact of increased utilization on the cost of care for multiple myeloma. Results: Following week 24, 671 (65%) of 1037 patients remained on daratumumab-containing regimens, with 330 patients continuing more frequent treatments than the expected once-every-4-weeks dosing described in the standard dosing schedule. Patients received an average of 14% more daratumumab doses than the FDA-approved label indicates, increasing the 1-year daratumumab costs by an estimated US$31,353. Conclusion: Daratumumab is utilized more frequently than the FDA-recommended dosing, leading to higher multiple myeloma treatment costs.

Lay abstract Since its first approval in 2015, daratumumab has become the backbone of many multiple myeloma treatment regimens. While its approval has improved outcomes in many patients who undergo treatment, it is expensive and has largely contributed to the increasing costs of care in multiple myeloma. In its most common treatment schedule, patients should transition from weekly and biweekly dosing to treatment once every 4 weeks. However, many providers maintain their patients on a more frequent dosing schedule, which increases Medicare 1-year costs by an estimated US$31,353 and may have unforeseen impacts on adverse events and patient outcomes.

Cost-effectiveness of adding durvalumab to first-line chemotherapy for extensive-stage small-cell lung cancer in China.

OBJECTIVES: Durvalumab plus chemotherapy could significantly improve overall survival compared with chemotherapy alone in the first-line treatment of extensive-stage small-cell lung cancer (SCLC). However, its long-term economic outcomes remain unclear yet. This study aimed to evaluate the cost-effectiveness of adding durvalumab to first-line chemotherapy for extensive-stage SCLC from the perspective of the Chinese health-care system. METHODS: A decision-analytic model with 10-year horizon was developed to estimate the health and economic outcomes of adding durvalumab to first-line treatment for extensive-stage SCLC. The primary outcomes included total costs, life years (LYs), quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER). Costs and utility values were obtained from the published literature. A scenario analysis for a patient assistance program (PAP) was conducted. Sensitivity analyses were performed to explore the robustness of the model outcomes. RESULTS: Durvalumab plus chemotherapy yielded additional 0.25 QALYs, with incremental costs of 76,354 USD, resulting in an ICER of 302,051 USD/QALY compared with chemotherapy alone, when PAP was available, the ICER was 192,591 USD/QALY. Sensitivity analyses confirmed the robustness of model outcomes. CONCLUSION: Adding durvalumab to first-line chemotherapy for extensive-stage small-cell lung cancer is unlikely to be cost-effectiveness in China.

Cost-effectiveness analysis of durvalumab plus etoposide: platinum in the first-line therapy of extensive stage small-cell lung cancer from the Chinese payers' perspective.

INTRODUCTION: Results from the CASPIAN trial (Durvalumab ± Tremelimumab in Combination With Platinum Based Chemotherapy in Untreated Extensive-Stage Small Cell Lung Cancer) trial demonstrated the clinical benefit of durvalumab plus etoposide-platinum (EP) chemotherapy as first-line treatment for patients with extensive stage small-cell lung cancer (ES-SCLC). However, considering the high price of durvalumab, it is unclear whether addition of durvalumab to EP chemotherapy has economic value compared with EP alone. In this study, we aimed to evaluate the cost-effectiveness of durvalumab plus EP chemotherapy as a first-line treatment for patients with ES-SCLC. METHODS: A Markov model comprising three health states (stable, progressive, and dead) was developed to simulate the process of small-cell lung cancer. Utility and costs were obtained from published resources. Health outcomes were derived from the CASPIAN trial. Costs were calculated based on the standard medical fees in Zhejiang Province from Chinese patients' perspective. Utility values were obtained from published data. One-way and probabilistic sensitivity analyses were applied to verify model robustness. RESULTS: The addition of durvalumab to EP chemotherapy costs more than $32,220, with a gain of 0.14 quality-adjusted life years (QALYs) compared with EP alone. The incremental cost-effective ratio was $230,142.9 per QALY, which exceeds the willingness to pay threshold of $28,527 per QALY. In the sensitivity analysis, the utility values for the progressive state, costs of durvalumab and EP chemotherapy, and costs for the progressive state were considered to be the three most sensitive factors in the model. CONCLUSION: The addition of durvalumab to EP chemotherapy is not a cost-effective strategy in the first-line therapy of ES-SCLC from the Chinese payers' perspective.

JAK inhibitors and monoclonal antibodies for the treatment of atopic dermatitis: effectiveness and value.

DISCLOSURES: Funding for this summary was contributed by Arnold Ventures, The Donaghue Foundation, Harvard Pilgrim Health Care, and Kaiser Foundation Health Plan to the Institute for Clinical and Economic Review (ICER), an independent organization that evaluates the evidence on the value of health care interventions. ICER's annual policy summit is supported by dues from AbbVie, America's Health Insurance Plans, Anthem, Alnylam, AstraZeneca, Biogen, Blue Shield of CA, Boehringer-Ingelheim, Cambia Health Services, CVS, Editas, Evolve Pharmacy, Express Scripts, Genentech/Roche, GlaxoSmithKline, Harvard Pilgrim, Health Care Service Corporation, HealthFirst, Health Partners, Humana, Johnson & Johnson (Janssen), Kaiser Permanente, LEO Pharma, Mallinckrodt, Merck, Novartis, National Pharmaceutical Council, Pfizer, Premera, Prime Therapeutics, Regeneron, Sanofi, Sun Life Financial, uniQure, and United Healthcare. Agboola, Herron-Smith, Nhan, Rind, and Pearson are employed by ICER. Through their affiliated institutions, Atlas, Brouwer, Carlson, and Hansen received funding from ICER for the work described in this summary.

Cost-effectiveness of adding daratumumab or bortezomib to lenalidomide plus dexamethasone for newly diagnosed multiple myeloma.

BACKGROUND: Multiple myeloma survival rates are steadily increasing due to availability of new drug classes used in combination with corticosteroids and chemotherapy. The latest treatments are daratumumab or bortezomib in combination therapy with lenalidomide and dexamethasone (Rd). Daratumumab, a CD38-targeted, human IgG1k monoclonal antibody, and bortezomib, a proteasome inhibitor, are both approved as regimens for transplant-ineligible relapsed/refractory multiple myeloma (RRMM). There have been cost-effectiveness analyses for daratumumab and bortezomib use in RRMM, but there are limited data regarding cost-effectiveness for daratumumab or bortezomib use in newly diagnosed multiple myeloma patients who are ineligible for stem cell transplantation. OBJECTIVE: To compare the cost-effectiveness of 3 separate regimens-(1) daratumumab, lenalidomide, and dexamethasone triple therapy (DRd); (2) bortezomib and lenalidomide plus dexamethasone triple therapy (VRd); and (3) lenalidomide plus dexamethasone (Rd)-in patients with multiple myeloma ineligible for autologous stem cell transplant. METHODS: A 2-state Markov model was developed using a US health system perspective and lifetime time horizon. Transition probabilities were calculated from the latest progression-free survival data reported in two phase 3 randomized controlled trials-MAIA and SWOG S0777-and extrapolated using a Weibull distribution based on the Hoyle Henley method. National data sources were used to obtain costs in 2019 US dollars, discounted by 3%. Health state utilities from available literature were applied to each health state. Utility decrements for adverse events were individualized in each choice branch with utility decrement weighted by the percentage of patients who experienced the adverse event in the MAIA and SWOG S0777 trials. We assumed a treatment would be cost-effective at a willingness to pay (WTP) of $150,000 per progression-free quality-adjusted life-year ($/PFQALY). One-way and probabilistic sensitivity analyses were conducted. RESULTS: Rd standard therapy had the lowest overall cost at $329,867, followed by VRd at $385,434 and DRd with the highest overall total cost at $626,900. Rd was estimated to result in the least amount (1.24) of PFQALYs, followed by VRd at 1.35 PFQALYs and DRd at 1.52 PFQALYs. With a WTP threshold of $150,000 per PFQALY, VRd was not cost-effective compared with Rd standard therapy, with an incremental cost-effectiveness ratio (ICER) of $530,256 per PFQALY. DRd was not cost-effective compared with VRd (ICER = $1,396,318 per PFQALY), nor as compared with Rd standard therapy (ICER = $1060,832). One-way sensitivity analysis showed that our model was sensitive to cost of DRd, VRd, and Rd drugs. Probabilistic sensitivity analysis showed that only at a WTP threshold of $550,000 was VRd cost-effective for 40% of iterations. There were no reasonable WTP thresholds, up to $800,00, where DRd became more cost-effective than VRd. CONCLUSIONS: This study is the first analysis to directly compare the cost-effectiveness of 3 acceptable chemotherapy treatment regimens for patients with multiple myeloma ineligible for autologous stem cell transplant. Neither DRd nor VRd triple therapy were found to be cost-effective vs Rd. Further cost-effectiveness analyses that include overall survival data for daratumumab and bortezomib triple therapies are needed to demonstrate an ICER in QALYs. DISCLOSURES: No funding was received for this study. At the time of this study, Narsipur was a UCSF-Actelion Clinical Research and Medical Communications Fellow, unrelated to this study. The other authors have nothing to disclose.

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

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

Cost-Effectiveness of Durvalumab After Chemoradiotherapy in Unresectable Stage III NSCLC: A US Healthcare Perspective.

BACKGROUND: Durvalumab was approved by the FDA in February 2018 for patients with unresectable stage III NSCLC that has not progressed after platinum-based concurrent chemoradiotherapy (cCRT), and this regimen is the current standard of care. The objective of this study was to examine the cost-effectiveness of durvalumab following cCRT versus cCRT alone in patients with locally advanced, unresectable stage III NSCLC. METHODS: A 3-state semi-Markov model was used. Modeling was performed in a US healthcare setting from Medicare and commercial payer perspectives over a 30-year time horizon. Clinical efficacy (progression-free and post progression survival) and utility inputs were based on PACIFIC study data (ClinicalTrials.gov identifier: NCT02125461; data cutoff March 22, 2018). Overall survival extrapolation was validated using overall survival data from a later data cutoff (January 31, 2019). The main outcome was the incremental cost-effectiveness ratio (ICER) of durvalumab following cCRT versus cCRT alone, calculated as the difference in total costs between treatment strategies per quality-adjusted life-year (QALY) gained. RESULTS: In the base-case analysis, durvalumab following cCRT was cost-effective versus cCRT alone from Medicare and commercial insurance perspectives, with ICERs of $55,285 and $61,111, respectively, per QALY gained. Durvalumab was thus considered cost-effective at the $100,000 willingness-to-pay (WTP) threshold. Sensitivity analyses revealed the model was particularly affected by variables associated with subsequent treatment, although no tested variable increased the ICER above the WTP threshold. Scenario analyses showed the model was most sensitive to assumptions regarding time horizon, treatment effect duration, choice of fitted progression-free survival curve, subsequent immunotherapy treatment duration, and use of a partitioned survival model structure. CONCLUSIONS: In a US healthcare setting, durvalumab was cost-effective compared with cCRT alone, further supporting the adoption of durvalumab following cCRT as the new standard of care in patients with unresectable stage III NSCLC.

The Budget Impact of Monoclonal Antibodies Used to Treat Metastatic Colorectal Cancer in Minas Gerais, Brazil.

INTRODUCTION: Biological medicines have increased the cost of cancer treatments, which also raises concerns about sustainability. In Brazil, three monoclonal antibodies (mAbs)-bevacizumab, cetuximab, and panitumumab-are indicated for the treatment of metastatic colorectal cancer (mCRC) but not currently funded by the Unified Health System (SUS). However, successful litigation has led to funding in some cases. OBJECTIVE: Our objective was to evaluate the budgetary impact of including the mAbs bevacizumab, cetuximab, and panitumumab in standard chemotherapy for the treatment of mCRC within the SUS of Minas Gerais (MG), Brazil. METHOD: A budget impact analysis of incorporating mAbs as first-line treatment of mCRC in MG was explored. The perspective taken was that of the Brazilian SUS, and a 5-year time horizon was applied. Data were collected from lawsuits undertaken between January 2009 and December 2016, and the model was populated with data from national databases and published sources. Costs are expressed in $US. RESULTS: In total, 351 lawsuits resulted in funding for first-line treatment with mAbs for mCRC. The three alternative scenarios analyzed resulted in cost increases of 348-395% compared with the reference scenario. The use of panitumumab had a budgetary impact of $US103,360,980 compared with the reference scenario over a 5-year time horizon, and bevacizumab and cetuximab had budgetary impacts of $US111,334,890 and 113,772,870, respectively. The use of the anti-epidermal growth factor receptor (EGFR) mAbs (cetuximab and panitumumab) is restricted to the approximately 41% of patients with KRAS mutations, so the best cost alternative for incorporation would be the combination of panitumumab and bevacizumab, with a cost of approximately $US106 million. CONCLUSION: These results highlight the appreciable costs for incorporating bevacizumab, cetuximab, and panitumumab into the SUS. Appreciable discounts are likely to be necessary before incorporation of these mAbs is approved.

Cost-utility analysis of the anti-TNF therapy for rheumatoid arthritis in a real-world based model.

BACKGROUND: Spending on drugs provided by the Brazilian Public Health System (BPHS) for the treatment of rheumatoid arthritis (RA) increased substantially with the beginning of the supply of biological disease-modifying anti-rheumatic drugs (bDMARD). This study aims to perform a cost-utility analysis of the most used biological drugs for the treatment of RA in Brazil. METHODS: a Markov model was used to carry out the cost-utility analysis. The data were obtained from a prospective cohort of RA patients using adalimumab, etanercept, and golimumab in Brazil. The BPHS perspective was adopted and the time horizon was five years. Deterministic and probabilistic sensitivity analyses were performed to evaluate the uncertainty. RESULTS: golimumab was the most cost-effective drug. Etanercept was dominated by golimumab. Adalimumab presented an incremental cost-utility ratio (ICUR) of $95,095.37 compared to golimumab in five years of follow-up. These results were confirmed by sensitivity analyses. CONCLUSION: the utility among adalimumab, etanercept, and golimumab was similar and the cost was the component that most impacted the economic model. Therefore, depending on the agreed price with the drug manufacturers, the incremental cost-utility ratio may vary among them.

A cost analysis study of the implementation of fixed-dosing of monoclonal antibodies in the Netherlands Cancer Institute.

Background There is a strong rationale for fixed-dosing of monoclonal antibodies in oncology. Although fixed-dosing of recently introduced monoclonal antibodies is well accepted, the rationale is also applicable for other monoclonal antibodies that already have been used for years, but are still body-size-based dosed in many hospitals. In the Netherlands Cancer Institute, Antoni van Leeuwenhoek (NKI-AVL), fixed-dosing has been implemented now for all monoclonal antibodies and, therefore, this site offers an ideal opportunity for a cost analysis study. Objective To investigate the financial impact of switching to fixed-dosing in the NKI-AVL. Setting The NKI-AVL. Method Information on the preparations of monoclonal antibodies was collected from August 2017 to February 2020. We compared the number of vials needed during preparation for fixed-dosing and body-size -based dosing strategies. The economic impact was calculated for 2 scenarios: scenario 1 assumed clustering of all preparations per day and scenario 2 assumed no clustering of preparations. Main outcome measure Number of saved vials and the correlating savings in health care costs. Results The implementation of fixed-dosing resulted in a substantial reduction in vials used for almost all monoclonal antibodies. The economic savings were calculated to be €0,8 and €3,1 million per year for scenario 1 and 2, respectively. Conclusion Fixed-dosing resulted in substantial savings in health care costs.

Development and economic trends in anticancer drugs licensed in the UK from 2015 to 2019.

Analysis of new anticancer drugs licensed in the UK found that 44 new therapies were approved from 2015 to 2019. No other 5-year period has produced as many new therapies. Most new drugs are kinase inhibitors (KIs, N=18) and monoclonal antibodies (mAbs, N=16) with only one classical cytotoxic chemotherapy (CC) licensed. The average median treatment duration has risen by 55 days to 318 days (263 days in 2010-2014). Drug costs have escalated; an average treatment course now costs £62 343, compared to £35 383 in 2010-2014. New drugs are delivering significant clinical benefits with longer treatment durations. However, the financial burden is greater, heralding economic challenges for healthcare providers.

Trends in list prices, net prices, and discounts of self-administered injectable tumor necrosis factor inhibitors.

BACKGROUND: List prices of tumor necrosis factor (TNF) inhibitors drastically increased during the last decade, but previous research has shown that half of these increases were offset by rising manufacturer discounts. It remains unclear to what extent manufacturers' discounts have offset increases in list prices of each self-administered injectable TNF inhibitor. Evaluating trends in net prices and discounts at the product level will be paramount in understanding the role of competition in the biologic market. OBJECTIVES: To (a) describe product-level changes in net prices of each self-administered injectable TNF inhibitor available in 2007-2019 and (b) quantify to what extent manufacturer discounts have offset increases in list prices. METHODS: We obtained 2007-2019 pricing data for etanercept, adalimumab, certolizumab, and golimumab from the investment firm SSR Health, which uses company-reported sales to estimate net prices and discounts for brand products manufactured by publicly traded companies. For each drug and year, we calculated annual costs of treatment for patients with rheumatoid arthritis based on list and net prices and discounts in Medicaid and other payers. RESULTS: From 2007-2019, list prices of etanercept and adalimumab increased by 293% and 295%, respectively; however, discounts offset 47% and 45% of these increases, leading to net price increases of 171% and 203%. List prices of golimumab and certolizumab increased by 183% and 182%, respectively, but with discounts offsetting 58% and 59% of these increases, net prices increased by 103% and 109%. Net prices of golimumab started to decrease after 2016, while net prices of adalimumab and certolizumab experienced their first drop in 2019. Across the study period, discounts in Medicaid and in other payers increased, respectively, from 21% to 85% and 6% to 32% for etanercept; from 26% to 88% and 19% to 35% for adalimumab; from 28% to 63% and 22% to 46% for golimumab; and from 29% to 83% and 27% to 47% for certolizumab. CONCLUSIONS: Despite growing manufacturer discounts, net prices of self-administered injectable TNF inhibitors still increased at a mean annual rate of 9.6% in 2007-2019. This led to net prices tripling for adalimumab and more than doubling for etanercept, golimumab, and certolizumab. DISCLOSURES: This study was funded by the Myers Family Foundation. Hernandez is funded by the National Heart, Lung and Blood Institute (grant number K01HL142847). Funding sources had no role in design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication. Hernandez has served on Pfizer's scientific advisory board. The other authors have nothing to disclose.

Poverty and Targeted Immunotherapy: Survival in Children's Oncology Group Clinical Trials for High-Risk Neuroblastoma.

BACKGROUND: Whether social determinants of health are associated with survival in the context of pediatric oncology-targeted immunotherapy trials is not known. We examined the association between poverty and event-free survival (EFS) and overall survival (OS) for children with high-risk neuroblastoma treated in targeted immunotherapy trials. METHODS: We conducted a retrospective cohort study of 371 children with high-risk neuroblastoma treated with GD2-targeted immunotherapy in the Children's Oncology Group trial ANBL0032 or ANBL0931 at a Pediatric Health Information System center from 2005 to 2014. Neighborhood poverty exposure was characterized a priori as living in a zip code with a median household income within the lowest quartile for the cohort. Household poverty exposure was characterized a priori as sole coverage by public insurance. Post hoc analyses examined the joint effect of neighborhood and household poverty using a common reference. All statistical tests were 2-sided. RESULTS: In multivariable Cox regressions adjusted for disease and treatment factors, household poverty-exposed children experienced statistically significantly inferior EFS (hazard ratio [HR] = 1.90, 95% confidence interval [CI] = 1.28 to 2.82, P = .001) and OS (HR = 2.79, 95% CI = 1.63 to 4.79, P < .001) compared with unexposed children. Neighborhood poverty was not independently associated with EFS or OS. In post hoc analyses exploring the joint effect of neighborhood and household poverty, children with dual-poverty exposure (neighborhood poverty and household poverty) experienced statistically significantly inferior EFS (HR = 2.21, 95% CI = 1.48 to 3.30, P < .001) and OS (HR = 3.70, 95% CI = 2.08 to 6.59, P < .001) compared with the unexposed group. CONCLUSIONS: Poverty is independently associated with increased risk of relapse and death among neuroblastoma patients treated with targeted immunotherapy. Incorporation of social and environmental factors in future trials as health-care delivery intervention targets may increase the benefit of targeted therapies.

Continuation of Anti-TNF in Patients With Ulcerative Colitis in Remission Is Not Cost-effective Compared With Treatment Withdrawal: A Markov Model.

BACKGROUND AND AIMS: Anti-tumour necrosis factor alpha [anti-TNF] treatment accounts for 31% of health care expenditures associated with ulcerative colitis [UC]. Withdrawal of anti-TNF in patients with UC in remission may decrease side effects and infections, while promoting cost containment. Approximately 36% of patients relapse within 12-24 months of anti-TNF withdrawal, but reintroduction of treatment is successful in 80% of patients. We aimed to evaluate the cost-effectiveness of continuation versus withdrawal of anti-TNF in patients with UC in remission. METHODS: We developed a Markov model comparing cost-effectiveness of anti-TNF continuation versus withdrawal, from a health care provider perspective. Transition probabilities were calculated from literature, or estimated by an expert panel of 11 gastroenterologists. Deterministic and probabilistic sensitivity analyses were performed to account for assumptions and uncertainty. The cost-effectiveness threshold was set at an incremental cost-effectiveness ratio of €80,000 per quality-adjusted life-year [QALY]. RESULTS: At 5 years, anti-TNF withdrawal was less costly [-€10,781 per patient], but also slightly less effective [-0.04 QALY per patient] than continued treatment. Continuation of anti-TNF compared with withdrawal costs €300,390/QALY, exceeding the cost-effectiveness threshold. Continued therapy would become cost-effective if the relapse rate following anti-TNF withdrawal was ≥43% higher, or if adalimumab or infliximab [biosimilar] prices fell below €87/40 mg and €66/100 mg, respectively. CONCLUSIONS: Continuation of anti-TNF in UC patients in remission is not cost-effective compared with withdrawal. A stop-and-reintroduction strategy is cost-saving but is slightly less effective than continued therapy. This strategy could be improved by identifying patients at increased risk of relapse.

US cost-effectiveness of polatuzumab vedotin, bendamustine and rituximab in diffuse large B-cell lymphoma.

Aim: To evaluate the cost-effectiveness of polatuzumab vedotin (pola) + bendamustine + rituximab (BR) in relapsed/refractory diffuse large B-cell lymphoma based on the GO29365 trial from a US payer's perspective. Materials & methods: A partitioned survival model used progression-free survival and overall survival data from the GO29365 trial. The base case analysis assumed overall survival was informed by progression-free survival; a mixture cure model estimated proportion of long-term survivors. Results: In the base case, pola + BR was cost-effective versus BR at US$35,864 per quality-adjusted life year gained. Probabilistic and one-way sensitivity analyses showed that the findings were robust. Conclusion: Pola + BR is cost-effective versus BR for the treatment of transplant-ineligible relapsed/refractory diffuse large B-cell lymphoma in the US.

Systematic Review: Monoclonal Antibody-Induced Subacute Cutaneous Lupus Erythematosus.

BACKGROUND: Subacute cutaneous lupus erythematosus (SCLE) lacks consensus diagnostic criteria and the pathogenesis is poorly understood. There are increasing reports of SCLE induced by monoclonal antibodies (mAbs), but there are limited data on the aetiology, clinical characteristics and natural course of this disease. METHODS: We devised a set of diagnostic criteria for SCLE in collaboration with a multinational, multispecialty panel. This systematic review employed a two-layered search strategy of five databases for cases of mAb-induced SCLE (PROSPERO registered protocol CRD42019116521). To explore the relationship between relative mAb use and the number of SCLE cases reported, the estimated number of mAb users was modelled from 2013 to 2018 global commercial data and estimated annual therapy costs. RESULTS: From 40 papers, we identified 52 cases of mAb-induced SCLE, occurring in a cohort that was 73% female and with a median age of 61 years. Fifty percent of cases were induced by anti-tumour necrosis factor (TNF)-ɑ agents. A median of three drug doses preceded SCLE onset and the lesions lasted a median of 7 weeks after drug cessation. Oral and topical corticosteroids were most frequently used. Of the licensed mAbs, adalimumab, denosumab, rituximab, etanercept and infliximab were calculated to have the highest relative number of yearly users based on global sales data. Comparing the number of mAb-induced SCLE cases with estimated yearly users, the checkpoint inhibitors pembrolizumab and nivolumab showed strikingly high rates of SCLE relative to their global use, but ipilimumab did not. CONCLUSION: We present the first systematic review characterising mAb-induced SCLE with respect to triggers, clinical signs, laboratory findings, prognosis and treatment approaches. We identify elevated rates associated with the use of checkpoint inhibitors and anti-TNFɑ agents.

Healthcare-Related Costs Associated with Switching Subcutaneous Tumor Necrosis Factor-α Inhibitor in the Treatment of Inflammatory Arthritis: a Retrospective Study.

INTRODUCTION: Subsequent lines of subcutaneous tumor necrosis factor alpha inhibitor (SC-TNFi) treatment may be well motivated in the management of rheumatoid arthritis (RA), ankylosing spondylitis (AS), and psoriatic arthritis (PsA)-collectively named inflammatory arthritis (IA). However, the costs associated with switching SC-TNFis are largely unknown. The objective of this retrospective observational study was to explore costs of healthcare resource utilization (HCRU) associated with switching SC-TNFi treatment among biologic-naïve Swedish patients with IA. METHODS: Using population-based register data, adult patients filling prescriptions between May 6, 2010 and December 31, 2014 for an SC-TNFi (adalimumab, etanercept, certolizumab, and golimumab) were included. Patients switching treatment (cyclers) were matched to treatment persistent patients on the basis of propensity score and follow-up time. HCRU-associated costs were captured and compared 12 months before and 12 months after the index date (defined as the date of the switch). RESULTS: A balanced cohort of 594 matched pairs was derived. Prior to the index date, cyclers had significantly higher non-treatment HCRU costs compared to persistent patients ($3815 [3498-4147] vs. $2900; 95%CI [2565-3256]). However, 12 months after the index date, cyclers had significantly increased their non-treatment HCRU costs while persistent patients lowered theirs ($822 [232-1490] vs. $- 313 [- 664-36]). This resulted in a statistically significant difference in difference of $1135 between the groups. CONCLUSIONS: In biologic-naïve patients treated with SC-TNFi for IA, cyclers significantly increased their non-treatment HCRU costs 12 months after switching treatment while persistent patients lowered their costs during the same time period. As these findings indicate that differences in treatment persistence may have an impact on costs, further research utilizing more comprehensive data sources in alternate settings is warranted.