Real-world analysis of cost, treatment patterns, and outcomes of patients with metastatic cutaneous squamous cell carcinoma in the US.

OBJECTIVES: To describe real-world characteristics and treatment patterns of patients with metastatic cutaneous squamous cell carcinoma (mCSCC). METHODS: This retrospective observational study used MarketScan Commercial and Medicare Supplemental claims databases (1/1/2013-7/31/2019). Adult patients with mCSCC who initiated non-immunotherapy systemic treatment (i.e. index event) between 1 January 2014 and 31 December 2018 were assessed for treatment patterns, all-cause and CSCC-related healthcare resource utilization, costs, and mortality . RESULTS: Overall, 207 patients were included in the study(mean age 64.8 years, 76.3% male), 59.4% had prior radiotherapy, and 58.9% had prior CSCC-related surgery. During follow-up, 75.8%, 51.7%, and 35.7% of patients received chemotherapy, radiotherapy, and targeted therapy as first-line treatment, respectively. Cisplatin (32.9%) and carboplatin (22.7%) were the most common chemotherapy agents, and cetuximab (32.4%) was the most common targeted therapy during the first-line.Probability of death (95% CI) at month 6, year 1, and year 2 was 24% (16-32%), 50% (40 - 59%), and 67% (56 - 75%), respectively. Average CSCC-related healthcare costs were $5,354 per person per month (PPPM), with outpatient costs being the major cost driver at 96.4% ($5,160 PPPM). CONCLUSION: During 2014-2018, patients with mCSCC were commonly treated with cisplatin and cetuximab; prognosis was generally poor. These results indicate opportunity for new treatments to improve survival outcomes.

Patient-reported outcomes labeling for oncology drugs: Multidisciplinary perspectives on current status and future directions.

Introduction: Regulatory agencies encourage the incorporation of the patient voices throughout clinical drug development. Patient-Reported Outcomes (PROs) offer one way of doing this and their use has markedly increased in many therapeutic areas, particularly oncology, in recent years. However, few oncology drug labels include PRO data and those which do, offer little consistency. Objective: To provide multidisciplinary perspectives (patient, pharmaceutical industry, PRO researcher, regulatory expert) on PRO data in oncology drug labels. Methods: PRO data in the labels of drugs approved by the Food and Drug Administration (FDA) and European Medicines Agency (EMA) for oncology indications between 2010 and 2020 were critically reviewed by authors who provided their insights on the advantages and disadvantages/gaps. Results: Forty-six oncology drugs included PRO data in their labels. Differences were observed between FDA and EMA PRO labeling (e.g., PRO concept, use of tables and graphs to display PROs or reference to clinical meaningfulness). In providing their perspectives on the number and nature of PROs in labels, authors noted limitations including: the low proportion of oncology drugs with PRO labeling, limited PRO information in labels, lack of patient-friendly language, and potential bias towards positive outcomes. Lack of consistency within- and between-agencies was noted. Conclusion: Despite regulatory agencies' commitment to incorporate patient voices in regulatory decisions, availability of PRO information is limited in oncology drug labels. While several PRO guidance documents are available from regulatory and Health Technology Assessment agencies, harmonization of PRO guidance for labeling inclusion around the world is needed to better inform prescribers and consequently their patients in the process of shared medical decisions.

A call to action to harmonize patient-reported outcomes evidence requirements across key European HTA bodies in oncology.

Patient-reported outcome (PRO) data are increasingly being included in Health Technology Assessment (HTA) submissions for oncology drugs. This study aims to provide differences in PRO evidence requirements in oncology across key HTA bodies and calls for its harmonization. Method guidance provided by HTA bodies in Germany, France and the UK, and analysis of HTA reports of 20 oncology case studies were evaluated in this review. Differences exist between HTA bodies regarding guidance on how PRO data should be collected, reported and analyzed as well as how the data are reviewed and considered in oncology HTAs. HTA bodies can play a key role to harmonize PRO method guidance in collaboration with regulators and sponsors.

Patient-reported outcomes (PRO) are information provided directly by the person who is experiencing a disease or undergoing a treatment, without additional interpretation by a clinician or caregiver. Along with other outcome measures, PROs may be included in the body of evidence used by health technology assessment bodies in their review. In this article, the authors summarize the guidance documents published by key health technology assessment agencies and reviewed 20 past cancer drug case studies to understand how different agencies use PROs when deciding on recommendations for new cancer treatments.

Real-World Treatment Patterns After CD19-Directed CAR T Cell Therapy Among Patients with Diffuse Large B Cell Lymphoma.

INTRODUCTION: CD19-directed chimeric antigen receptor T cells (CAR T) are approved for treatment of adults with relapsed/refractory diffuse large B cell lymphoma (DLBCL) following at least two lines of therapy. METHODS: This study describes real-world treatment patterns after CAR T in adults with DLBCL. It includes adults diagnosed with DLBCL in IBM MarketScan Commercial and Medicare Supplemental healthcare claims databases administered CAR T between 2017 and 2019 (index event) and at least 6 months of continuous health plan enrollment pre-index. Kaplan-Meier methods were used to estimate risk and time to first subsequent treatment after CAR T, as a proxy for CAR T failure. RESULTS: Among 129 patients meeting study criteria, most (123; 95.4%) were hospitalized during CAR T therapy. Median length of stay was 17 (25th-75th percentile, 13-22) days. Estimated 6-month risk of subsequent treatment was 36.2% (95% confidence interval [CI] 27.1-45.8%). During median follow-up of 195 (25th-75th percentile, 102-362) days, median time to the first line of therapy after CAR T, accounting for censoring, was 378 days (95% CI 226, not reached). Among 48 patients who received another therapy after CAR T, 58.3% received immunotherapy, 50.0% radiation therapy, 25.0% chemotherapy, 25.0% targeted therapy, and 12.5% hematopoietic stem cell transplant. CONCLUSIONS: Among real-world patients with DLBCL treated with CAR T, the risk of not achieving a durable response is considerable; additional, effective options for DLBCL salvage treatment are needed.

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

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

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

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

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

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

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

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

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

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

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

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

Sarilumab monotherapy compared with adalimumab monotherapy for the treatment of moderately to severely active rheumatoid arthritis: an analysis of incremental cost per effectively treated patient.

PURPOSE: Treatment outcomes and direct medical costs were examined, from a US health payer perspective, of monotherapy with sarilumab 200 mg subcutaneous (SC) every 2 weeks (Q2W) vs adalimumab 40 mg SC Q2W/QW in adult patients with moderately to severely active rheumatoid arthritis who are intolerant of, inadequate responders to, or considered inappropriate candidates for continued methotrexate treatment. PATIENTS AND METHODS: Short-term analysis was based on 24-week wholesale acquisition costs of drugs and treatment response observed in the MONARCH Phase III trial (NCT02332590) per American College of Rheumatology (ACR) 20/50 criteria and European League Against Rheumatism (EULAR) Moderate/Good Disease Activity Score 28-joint count erythrocyte sedimentation rate. Long-term analysis, which also considered drug administration and routine care costs, was conducted via a 6-month decision tree and a 1- to 10-year Markov model with microsimulation of patient profiles from the MOBILITY Phase III trial (NCT01061736). Utilities and quality-adjusted life-years (QALYs) were estimated by mapping 6-month ACR levels to a relative change in Health Assessment Questionnaire - Disability Index score and via published algorithms. RESULTS: For sarilumab and adalimumab, respectively, 24-week drug costs were $18,954 and $29,232, and costs per responder were $26,435 vs $50,055 on ACR20; $41,475 vs $98,425 on ACR50; and $22,511 vs $41,230 on EULAR Moderate/Good. Base case results at 10 years for total costs and QALYs were $176,977 and 2.75 for sarilumab and $212,136 and 2.61 for adalimumab, respectively. Sarilumab was consistently the more effective and cost-saving treatment across all short-term and long-term incremental analyses. CONCLUSION: Sarilumab monotherapy was the economically dominant treatment on incremental cost per responder and incremental cost per QALY compared with adalimumab monotherapy. These results were maintained within the sensitivity analyses.

Budget impact analysis of sarilumab for the treatment of rheumatoid arthritis in patients with an inadequate response to conventional synthetic DMARD or TNF inhibitor therapies.

OBJECTIVE: To estimate the 5-year budget impact (BI) on a US health plan of introducing sarilumab - a human immunoglobulin G1 anti-IL-6 receptor α monoclonal antibody - as combination treatment with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs) or monotherapy in patients with moderate-to-severe rheumatoid arthritis (RA). METHODS: BI analysis was conducted from a commercial payer perspective. Treatment-eligible populations included adult patients with moderate-to-severe RA and inadequate response (IR) to csDMARDs or tumor necrosis factor (TNF)-α inhibitors-IR. All licensed biologic treatments recommended by the American College of Rheumatology guidelines were included. RESULTS: For a hypothetical plan of one million members, 409 csDMARD-IR and 345 TNF-IR patients were annually eligible for combination therapy and 226 csDMARD and TNF-IR patients for monotherapy with sarilumab. Based on 2018 US direct treatment costs, the introduction of sarilumab was estimated to save $526,424, $322,637 and $264,306 over 5 years for csDMARD-IR combination therapy patients, TNF-IR combination therapy patients, and csDMARD-IR/TNF-IR monotherapy patients, respectively. As sarilumab absorbed a greater market share over the horizon, annual savings increased from years 1 to 5, $28,610 (-0.14%) to $194,646 (-0.83%) in csDMARD-IR, $16,986 (-0.11%) to $120,893 (-0.67%) in TNF-IR, and $14,256 (-0.13%) to $98,040 (-0.79%) in monotherapy. One-way sensitivity analyses revealed that the model was most sensitive to variations in sarilumab adherence. CONCLUSION: Total cost savings of introducing sarilumab to a health-care plan accrued from years 1 to 5, attributable to the lower treatment cost, stable dosing paradigm, and price parity for the two available doses (150 and 200 mg every 2 weeks) compared with alternative biologic DMARDs that have substantial variability in dose titration/schedules.

Treatment Persistence and Healthcare Costs Among Patients with Rheumatoid Arthritis After a Change in Targeted Therapy.

BACKGROUND: Targeted disease-modifying antirheumatic drug (DMARD) options for rheumatoid arthritis (RA) include tumor necrosis factor (TNF) inhibitors (adalimumab, certolizumab, etanercept, golimumab, infliximab) or alternative mechanisms of action (MOAs), such as a T-cell co-stimulation modulator (abatacept), Janus kinase inhibitor (tofacitinib), or interleukin-6 inhibitor (tocilizumab). OBJECTIVE: To examine treatment persistence and healthcare costs in patients with RA who changed therapy by cycling therapy (ie, switching within the same drug class), or switching between, the TNF inhibitors and alternative MOA medication classes. METHODS: We analyzed medical and pharmacy claims for commercially insured patients who cycled or switched between targeted DMARD agents between January 1, 2010, and September 30, 2014 (ie, the index date), to determine treatment patterns (ie, treatment switching, discontinuation, restarting after a gap ≥60 days, or persistence) and costs (plan- and patient-paid) for 1 year postindex. The cost per persistent patient was the total healthcare cost divided by the number of treatment-persistent patients. RESULTS: The analysis included 6203 patients who cycled between TNF inhibitors, 2640 patients who switched from TNF inhibitors to alternative MOA agents, 699 patients who cycled between alternative MOA agents, and 687 patients who switched from alternative MOA agents to TNF inhibitors. The 1-year treatment persistence rates (with P values vs TNF inhibitor cyclers) were 45.2% for TNF inhibitor cyclers, 50.3% for TNF inhibitor-alternative MOA switchers (P <.001), 51.4% for alternative MOA agent cyclers (P = .002), and 46.1% for alternative MOA-TNF inhibitor switchers (P = .63). Compared with TNF inhibitor cyclers, the cost per persistent patient was lower for TNF inhibitor-alternative MOA switchers (-$16,853 RA-related; -$19,280 targeted DMARDs), alternative MOA agent cyclers (-$21,662 RA-related; -$25,153 targeted DMARDs), and alternative MOA-TNF inhibitor cyclers (-$7206 RA-related; -$7919 targeted DMARDs). CONCLUSION: Among patients with RA, patients who switched from a TNF inhibitor to an alternative MOA agent and those who cycled between alternative MOA agents had significantly higher treatment persistence rates and a substantially lower cost per persistent patient than those who cycled between TNF inhibitors. These findings support the evaluation of switching medication classes for patients with RA when a targeted therapy fails.

Burden of rheumatoid arthritis among US Medicare population: co-morbidities, health-care resource utilization and costs.

OBJECTIVES: The study aimed to assess the burden of RA among the US Medicare population (aged ≥65 years) by comparing co-morbidities, health-care resource utilization (HCRU) and costs against matched non-RA Medicare patients. METHODS: Data were obtained from the Medicare fee-for-service claims database from 2010 to 2013. RA Medicare patients were identically matched with Medicare patients without RA (controls) based on demographics. Bivariate analyses were conducted to examine differences between cohorts for co-morbidities, HCRU and costs. A generalized linear model was used to test relationships between patient-level characteristics, HCRU and costs. RESULTS: The study population included 115 867 RA patients and 115 867 age-, sex-, race- and region-matched non-RA controls. Mean age was 75.2 years; 79.4% were female. Co-morbidities were greater in RA vs non-RA patients [Charlson Co-morbidity Index (excluding RA): 1.86 vs 1.00; P < 0.0001]. All-cause annual HCRU was greater in RA vs non-RA patients. Total annual health-care costs were ∼3-fold higher in RA vs non-RA patients ($20 919 vs $7197, respectively; P < 0.0001) with the major driver of costs in the RA cohort being outpatient costs. Approximately half of the overall costs in the RA cohort were RA related ($11 587). After controlling for differences in patient characteristics and co-morbidities between cohorts, the adjusted total mean annual costs for RA patients were still more than twice those of non-RA patients ($16 374 vs $6712; P < 0.0001). CONCLUSIONS: Among US Medicare patients, those with an RA diagnosis had a significantly greater burden of co-morbidities, HCRU and costs compared with a matched cohort without RA.

Treatment Persistence and Healthcare Costs Among Patients with Rheumatoid Arthritis Changing Biologics in the USA.

INTRODUCTION: After a patient with rheumatoid arthritis (RA) fails tumor necrosis factor inhibitor (TNFi) treatment, clinical guidelines support either cycling to another TNFi or switching to a different mechanism of action (MOA), but payers often require TNFi cycling before they reimburse switching MOA. This study examined treatment persistence, cost, and cost per persistent patient among MOA switchers versus TNFi cyclers. METHODS: This study of Commercial and Medicare Advantage claims data from the Optum Research Database included patients with RA and at least one claim for a TNFi (adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab) between January 2012 and September 2015 who changed to another TNFi or a different MOA therapy (abatacept, tocilizumab, or tofacitinib) within 1 year. The index date was the date of the change in therapy. Treatment persistence was defined as no subsequent switch or 60-day gap in therapy for 1 year post-index. RA-related costs included plan-paid and patient-paid amounts for inpatient, outpatient, and pharmacy claims. Medication costs included index and post-index costs of TNFi and different MOA therapies. RESULTS: There were 581 (38.3%) MOA switchers and 935 (61.7%) TNFi cyclers. The treatment persistence rate was significantly higher for MOA switchers versus TNFi cyclers (47.7% versus 40.2%, P = 0.004). Mean 1-year healthcare costs were significantly lower among MOA switchers versus TNFi cyclers for total RA-related costs ($37,804 versus $42,116; P < 0.001) and medication costs ($29,001 versus $34,917; P < 0.001). When costs were divided by treatment persistence, costs per persistent patient were lower among MOA switchers versus TNFi cyclers: $25,436 lower total RA-related cost and $25,999 lower medication costs. CONCLUSION: MOA switching is associated with higher treatment persistence and lower healthcare costs than TNFi cycling. Reimbursement policies that require patients to cycle TNFi before switching MOA may result in suboptimal outcomes for both patients and payers. FUNDING: Sanofi and Regeneron Pharmaceuticals.

Outcomes of tumor necrosis factor inhibitor cycling versus switching to a disease-modifying anti-rheumatic drug with a new mechanism of action among patients with rheumatoid arthritis.

OBJECTIVES: To examine treatment patterns, treatment effectiveness, and treatment costs for 1 year after patients with rheumatoid arthritis switched from a tumor necrosis factor inhibitor (TNFi) (adalimumab, certolizumab pegol, etanercept, golimumab, or infliximab), either cycling to another TNFi ("TNFi cyclers") or switching to a new mechanism of action (abatacept, tocilizumab, or tofacitinib) ("new MOA switchers"). METHODS: This retrospective cohort study used administrative claims data for a national insurer. Treatment persistence (without switching again, restarting, or discontinuing), treatment effectiveness (defined below), and costs were assessed for the 12-month post-switch period. Patients were "effectively treated" if they satisfied all six criteria for a treatment effectiveness algorithm (high adherence, no dose increase, no new conventional synthetic disease-modifying anti-rheumatic drug, no subsequent switch in therapy, no new/increased oral glucocorticoids, and <2 glucocorticoid injections). Multivariable logistic models were used to adjust for baseline factors. RESULTS: The database included 581 new MOA switchers and 935 TNFi cyclers. New MOA switchers were 39% more likely than TNFi cyclers to persist after the switch (odds ratio [OR] = 1.39; 95% confidence interval [CI] = 1.12-1.74; p = .003) and 36% less likely to switch therapy again (OR = 0.64; 95% CI = 0.51-0.81; p < .001). New MOA switchers were 43% more likely than TNFi cyclers to be effectively treated (OR = 1.43; 95% CI = 1.11-1.85; p = .006). New MOA switchers had 16% lower drug costs than TNFi cyclers (cost ratio = 0.84; 95% CI = 0.79-0.88; p < .001) and 11% lower total costs of rheumatoid arthritis-related medical care (cost ratio = 0.89; 95% CI = 0.84-0.94; p < .001). LIMITATIONS: Claims payments may not reflect rebates or other cost offsets. Medical and pharmacy claims do not include clinical end-points or reasons that lead to new MOA switching vs TNFi cycling. CONCLUSIONS: These results support switching to a new MOA after a patient fails treatment with a TNFi, which is consistent with recent guidelines for the pharmacologic management of established rheumatoid arthritis.

The health and economic impact of vaccination with 7-valent pneumococcal vaccine (PCV7) during an annual influenza epidemic and influenza pandemic in China.

BACKGROUND: China has experienced several severe outbreaks of influenza over the past century: 1918, 1957, 1968, and 2009. Influenza itself can be deadly; however, the increase in mortality during an influenza outbreak is also attributable to secondary bacterial infections, specifically pneumococcal disease. Given the history of pandemic outbreaks and the associated morbidity and mortality, we investigated the cost-effectiveness of a PCV7 vaccination program in China from the context of typical and pandemic influenza seasons. METHODS: A decision-analytic model was employed to evaluate the impact of a 7-valent pneumococcal vaccine (PCV7) infant vaccination program on the incidence, mortality, and cost associated with pneumococcal disease during a typical influenza season (15% flu incidence) and influenza pandemic (30% flu incidence) in China. The model incorporated Chinese data where available and included both direct and indirect (herd) effects on the unvaccinated population, assuming a point in time following the initial introduction of the vaccine where the impact of the indirect effects has reached a steady state, approximately seven years following the implementation of the vaccine program. Pneumococcal disease incidence, mortality, and costs were evaluated over a one year time horizon. Healthcare costs were calculated using a payer perspective and included vaccination program costs and direct medical expenditures from pneumococcal disease. RESULTS: The model predicted that routine PCV7 vaccination of infants in China would prevent 5,053,453 cases of pneumococcal disease and 76,714 deaths in a single year during a normal influenza season.The estimated incremental-cost-effectiveness ratios were ¥12,281 (US$1,900) per life-year saved and ¥13,737 (US$2,125) per quality-adjusted-life-year gained. During an influenza pandemic, the model estimated that routine vaccination with PCV7 would prevent 8,469,506 cases of pneumococcal disease and 707,526 deaths, and would be cost-saving. CONCLUSIONS: Routine vaccination with PCV7 in China would be a cost-effective strategy at limiting the negative impact of influenza during a typical influenza season. During an influenza pandemic, the benefit of PCV7 in preventing excess pneumococcal morbidity and mortality renders a PCV7 vaccination program cost-saving.

Persistence and adherence with urinary antispasmodic medications among employees and the impact of adherence on costs and absenteeism.

BACKGROUND: Overactive bladder (OAB) and related conditions, such as urge urinary incontinence (UI), can interfere with work, leisure activities, and healthy sleep patterns. OBJECTIVES: To report (a) employee urinary antispasmodic (UA) medication persistence and adherence; (b) the impact of salary and copay on adherence; and (c) the impact of UA adherence on medical, pharmacy, sick leave (SL), short- and long-term disability (STD, LTD), workers' compensation costs, work absence days, and turnover. METHODS: This retrospective study used a 2001-2011 database of claims, payroll, and demographic data from 27 large U.S. employers. Employees aged 18-64 years taking UA medications with health plan enrollment from 6 months before the index UA medication prescription to 12 months after were included. Persistence (days until first ≥ 30-day gap in UA medication supply) and adherence (percentage of the annual post-index period with available medication) were assessed using survival analysis and generalized linear regression models that controlled for demographics, job-related factors, copay, and pre-index employee benefit utilization.  RESULTS: 2,960 employees met study criteria. Median days of persistence by OAB subtype were 76, 82, 43, 66, and 60 for urge UI, mixed UI, nocturnal UI, other OAB, and no diagnosis, respectively (P less than 0.05 for urge and mixed vs. no diagnosis). Increased copay and copay as a percentage of salary were associated with lower adherence. Employees with ≥ 80% adherence had lower medical, SL, and STD and higher overall drug costs than employees with less than 80% adherence.  CONCLUSIONS: This study suggests potential economic benefits to employers from increased UA adherence. Additionally, economic factors such as ability to pay influence adherence to UA medications.

Economic burden of urge urinary incontinence in the workplace.

OBJECTIVE: Quantify incremental employee medical, pharmacy, sick leave, short- and long-term disability, and workers' compensation costs, absence days, and turnover associated with urge urinary incontinence (UUI) in employees. METHODS: This retrospective 2001-2011 database comparison of employees with UUI versus those without UUI (controls) included employees aged 18.5 to 64.0 years at index, with 6-month preindex and 12-month postindex health plan enrollment. Logistic and generalized linear models measured postindex costs, absences, and turnover. RESULTS: The study included 1448 employees with UUI and 337,796 controls. Employees with UUI had statistically significantly higher medical (131% higher), pharmacy (52%), sick leave (30%), and short-term disability (74%) costs and more sick leave (22%) and short-term disability (99%) days than controls (all P < 0.02). CONCLUSIONS: Employees with UUI had 117% greater medical and pharmacy costs, 47% greater total absence costs, and 63% more absence days than employees without UUI.

Economic burden of urgency urinary incontinence in the United States: a systematic review.

BACKGROUND: The International Continence Society (ICS) identifies several urinary incontinence (UI) subtypes: urgency urinary incontinence (UUI), stress UI (SUI), and mixed UI (MUI). UUI is a common symptom of overactive bladder (OAB) syndrome. Based on the current ICS definition of OAB, all patients with UUI have OAB, whereas not all patients with OAB have UUI. Because UUI is a chronic condition that is expected to increase in prevalence as the population of elderly individuals grows, it is important to understand its economic burden on society and patients and its cost components.  OBJECTIVE: To summarize the published English language medical literature on estimates of the economic burden of UUI in the United States from a societal and patient perspective, including direct costs (diagnosis, treatment, routine care [including incontinence pads], and UUI-associated comorbidities/complications); indirect costs (lost wages by patients and caregivers and lost work productivity due to absenteeism and presenteeism); and intangible costs (pain, suffering, and decreased health-related quality of life).  METHODS: A PubMed search of the literature for articles on the economic burden of UUI in the United States was conducted using the search terms (urgency urinary incontinence OR urge incontinence OR mixed incontinence OR overactive bladder) AND (burden OR cost OR economic) AND (United States), with limits for English language, publication from 1991 to 2011, humans, and adults (19+ years). Only primary articles of non-neurogenic UUI in the United States were retained.  RESULTS: Seven studies were identified that included data on the economic burden of UUI in the United States from a societal and patient perspective. Although estimates of the total economic burden of UUI include direct, indirect, and intangible costs, none of the 7 U.S. studies included all of these cost components. Furthermore, the costs of UUI often could not be fully extracted from the costs of OAB, which include patients with and without UUI, or the costs of other types of UI. The most recent cost analysis incorporated OAB with UUI prevalence rates and data on use of each cost component to calculate the total annual direct costs in 2007 for adults aged ≥ 25 years. The estimated total national cost of OAB with UUI in 2007 was $65.9 billion, with projected costs of $76.2 billion in 2015 and $82.6 billion in 2020. This 2007 estimate was markedly higher than those reported in older studies. Direct costs are the main driver of the overall cost of UUI in the United States. Studies that assessed patient costs indicated that the personal costs of routine care items for UUI and MUI represent a meaningful contribution to the overall economic burden of these conditions. These substantial personal expenditures may explain why patients reported that they were willing to pay considerable amounts for a treatment that would reduce the frequency of their UUI episodes.  CONCLUSIONS: UUI in the United States is associated with a substantial economic burden from both a societal and patient perspective. Studies evaluating the impact of interventions that reduce the frequency of UUI episodes on the overall economic burden of UUI are warranted.