Access to biologics and Janus kinase inhibitors for treatment of rheumatic diseases in the biosimilars era in Poland: a nation-level study.

INTRODUCTION: By reducing treatment costs, biosimilars provide an opportunity to improve accessibility to highly effective drugs. OBJECTIVES: This study aimed to evaluate access to biologic disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKis) among patients with rheumatic musculoskeletal diseases within a 10 year timeframe in Poland. PATIENTS AND METHODS: We performed a retrospective analysis using a nationwide public payer database. RESULTS: By 2022, 11 102, 6602, and 4400 patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), and axial spondyloarthritis (axSpA) were treated with bDMARDs or JAKis. Peak drug utilization was observed for adalimumab, followed by etanercept and tocilizumab. Within the study timeframe, the estimated access to innovative drugs increased from 0.8%, 1.4%, and 0.8% to 3.2%, 8.7%, and 3.5% for RA, PsA, and axSpA patients, respectively. Affordable tumor necrosis factor inhibitors (TNFis) still predominate among innovative therapeutics, but their market share declined from 87% to 46%. The number of patients treated with other bDMARDs/JAKis almost doubled within the prespecified timeframe. Overall, the average annual treatment cost per patient decreased by 60%, from 7315 EUR to 2886 EUR. Despite recent safety warnings, JAKis appear to be increasingly utilized. Additional analyses regarding the COVID­19 pandemic showed impaired access to intravenous therapies, but not subcutaneous or oral formulations. CONCLUSIONS: In Poland, biosimilars­related savings improved availability of higher­priced innovative drugs rather than less costly TNFis. Data­driven resource allocation and dedicated policy solutions facilitating access to affordable biologics are recommended.

Number needed to treat and cost per responder of Janus kinase inhibitors approved for the treatment of moderate-to-severe rheumatoid arthritis in Japan.

OBJECTIVE: This study evaluated the effectiveness and cost-effectiveness of baricitinib, tofacitinib, and upadacitinib regimens, compared to conventional synthetic disease-modifying antirheumatic drug (csDMARD) alone, among Japanese patients with moderate-to-severe rheumatoid arthritis (RA) inadequately responsive to csDMARD, measured in terms of number needed to treat (NNT) and cost per responder (CPR). METHODS: Efficacy data were derived from two recent network meta-analyses among global and Japanese population. The cost perspective was that of the Japanese Health Service. Both NNT and CPR were based on disease activity score for 28 joints with C-reactive protein (DAS28-CRP) remission and American College of Rheumatology (ACR) 20/50/70 at 12 and 24 weeks. RESULTS: Over 12 weeks, the median NNT and the median CPR to achieve DAS28-CRP remission were 4.3 and JPY 1,799,696 [USD 16,361], respectively, for upadacitinib 15 mg + csDMARD. The equivalent results were 6.0 and JPY 2,691,684 [USD 24,470] for baricitinib 4 mg + csDMARD and 5.6 and JPY 2,507,152 [USD 22,792] for tofacitinib 5 mg + csDMARD. Similar rankings were observed at 24 weeks and for other outcomes. CONCLUSIONS: Upadacitinib 15 mg was associated with the lowest NNT and CPR among the three Janus kinase inhibitors used in treatment regimens for Japanese patients with moderate-to-severe RA inadequately responsive to csDMARD.

Treatment patterns and health care costs among patients with psoriatic arthritis treated with biologic or targeted synthetic disease-modifying antirheumatic drugs.

BACKGROUND: Biologic and targeted synthetic disease-modifying antirheumatic drug (tsDMARD) therapies are used in management of psoriatic arthritis (PsA). Although previous studies have demonstrated that rates of adherence, persistence, discontinuation, and switching, as well as health care costs, are variable among treatments, limited published data exist on more recently approved therapies. OBJECTIVE: To describe adherence, persistence, discontinuation, reinitiation, switching, dosing patterns, and health care costs among PsA patients treated with biologics and tsDMARDs. METHODS: This was a real-world, retrospective administrative claims study. Adult PsA patients with at least 1 claim for an approved PsA biologic (adalimumab, certolizumab, etanercept, golimumab, infliximab, secukinumab, or ustekinumab) or tsDMARD (apremilast or tofacitinib) between January 1, 2015, and June 30, 2019, were selected from the IBM MarketScan administrative claims databases. The first claim for one of the study treatments determined the index date and drug cohort. Patients were required to be continuously enrolled in their health plans for 12 months before and after the index date and to have at least 1 claim with a diagnosis of PsA in the 12 months before or on the index date. Adherence (measured by proportion of days covered [PDC] and medication possession ratio [MPR]), persistence (< 60-day gap in treatment), discontinuation (> 90-day gap), reinitiation of index drug, switching, and dosing patterns for each index drug were assessed during the 12-month follow-up period. Health care costs were reported per patient per month (PPPM) during the 12-month follow-up and assessed after adjusting PsA treatment costs by the Institute for Clinical and Economic Review discount factors to account for discounts and rebates not usually reflected in claims data and by adherence. RESULTS: Overall, 6,674 patients met the selection criteria. The top 3 index drugs were adalimumab (37%), apremilast (26%), and etanercept (18%). Over 12 months of follow-up, 31%-59% of patients remained persistent on the index drug, whereas 35%-56% discontinued, 13%-29% switched to a different biologic or tsDMARD, and 3%-15% reinitiated the index therapy, depending on the index drug. The mean PDC ranged from 0.51 to 0.69 during the 12-month follow-up and 0.80 to 0.93 during the follow-up period before discontinuation. Dose values were largely consistent with prescribing information, with the exception of secukinumab. Index drug costs PPPM ranged from $2,361 (apremilast) to $6,528 for ustekinumab after adjustment for discounts and adherence. CONCLUSIONS: Results from this real-world analysis suggest that there is substantial variability in persistence, discontinuation, adherence, reinitiating, and switching patterns among the different biologic and tsDMARD treatment options for PsA patients. In addition, this study provides real-world cost data for biologics and tsDMARDs among patients with PsA. DISCLOSURES: This study was funded by Eli Lilly Inc., which participated in analysis and interpretation of data, drafting, reviewing, and approving the publication. All authors contributed to the development of the publication and maintained control over the final content. Murage, Malatestinic, Zhu, Atiya, Kern, Stenger, and Sprabery are employees and stockholders of Eli Lilly Inc. Princic and Park are employed by IBM Watson Health, which received funding from Eli Lilly Inc. to conduct this study. Ogdie has received consulting fees from Amgen, AbbVie, Bristol-Myers Squibb, Celgene, Corrona, Janssen, Lilly, Novartis, and Pfizer and has also received grant support from Pfizer, Novartis, and Amgen. Portions of these data have been presented in poster form at the virtual International Society for Pharmacoeconomics and Outcomes Research (ISPOR) 2020 and Congress of Clinical Rheumatology (CCR) West 2020 conferences.

Cost-Effectiveness Analysis of Biopharmaceuticals for Treating Rheumatoid Arthritis: Infliximab, Adalimumab, and Etanercept.

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic progressive inflammatory disease that causes joint destruction. The condition imposes a significant economic burden on patients and societies. The present study is aimed at evaluating the cost-effectiveness of Infliximab, Adalimumab, and Etanercept in treating rheumatoid arthritis in Iran. METHODS: This is a cost-effectiveness study of economic evaluation in which the Markov model was used. The study was carried out on 154 patients with rheumatoid arthritis in Fars province taking Infliximab, Adalimumab, and Etanercept. The patients were selected through sampling. In this study, the cost data were collected from a community perspective, and the outcomes were the mean reductions in DAS-28 and QALY. The cost data collection form and the EQ-5D questionnaire were also used to collect the required data. The results were presented in the form of an incremental cost-effectiveness ratio, and the sensitivity analysis was used to measure the robustness of the study results. The TreeAge Pro and Excel softwares were used to analyze the collected data. RESULTS: The results showed that the mean costs and the QALY rates in the Infliximab, Adalimumab, and Etanercept arms were $ 79,518.33 and 12.34, $ 91,695.59 and 13.25, and $ 87,440.92 and 11.79, respectively. The one-way sensitivity analysis confirmed the robustness of the results. In addition, the results of the probabilistic sensitivity analysis (PSA) indicated that on the cost-effectiveness acceptability curve, Infliximab was in the acceptance area and below the threshold in 77% of simulations. The scatter plot was in the mentioned area in 81% and 91% of simulations compared with Adalimumab and Etanercept, respectively, implying lower costs and higher effectiveness than the other two alternatives. Therefore, the strategy was more cost-effective. CONCLUSION: According to the results of this study, Infliximab was more cost-effective than the other two medications. Therefore, it is recommended that physicians use this medication as the priority in treating rheumatoid arthritis. It is also suggested that health policymakers consider the present study results in preparing treatment guidelines for RA.

Economic Benefit from Improvements in Quality of Life with Upadacitinib: Comparisons with Tofacitinib and Methotrexate in Patients with Rheumatoid Arthritis.

INTRODUCTION: To compare the economic benefit of upadacitinib combination therapy versus tofacitinib combination therapy and upadacitinib monotherapy versus methotrexate monotherapy from improvements in health-related quality of life (HRQOL) in patients with rheumatoid arthritis (RA). METHODS: Data were analyzed from two trials of upadacitinib (SELECT-NEXT and SELECT-MONOTHERAPY) and one trial of tofacitinib (ORAL-Standard) that collected HRQOL measurements using the Short Form 36 (SF-36) Health Survey in patients with RA. Direct medical costs per patient per month (PPPM) for patients receiving upadacitinib 15 mg once daily and methotrexate were derived from observed SF-36 Physical (PCS) and Mental Component Summary (MCS) scores in the SELECT trials using a regression algorithm. Direct medical costs PPPM for patients receiving tofacitinib 5 mg twice daily were obtained from a published analysis of SF-36 PCS and MCS scores observed in the ORAL-Standard trial. Short-term (12-14 weeks) and long-term (48 weeks) estimates of direct medical costs PPPM were compared between upadacitinib and tofacitinib and between upadacitinib and methotrexate. RESULTS: Over 12 weeks, direct medical costs PPPM were $252 lower (95% CI $72, $446) for upadacitinib-treated patients versus tofacitinib-treated patients. Medical costs PPPM at weeks 24 and 48 and cumulative costs over the entire 48-week period (difference $1759; 95% CI $1162, $2449) were significantly lower for upadacitinib than for tofacitinib. Over 14 weeks, direct medical costs PPPM were $399 lower (95% CI $158, $620) for patients treated with upadacitinib monotherapy compared with those treated with methotrexate alone. Direct medical costs at week 48 and cumulative costs over the entire 48-week period (difference $2044; 95% CI $1221, $2846) were significantly lower for upadacitinib monotherapy compared with methotrexate alone. CONCLUSION: In the short and long term, upadacitinib combination therapy versus tofacitinib combination therapy and upadacitinib monotherapy versus methotrexate monotherapy were associated with significantly lower direct medical costs for patients with RA. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT02675426, NCT02706951, and NCT00853385.

Guided therapy selection in rheumatoid arthritis using a molecular signature response classifier: an assessment of budget impact and clinical utility.

BACKGROUND: Patients with moderate to severe rheumatoid arthritis (RA) can be treated with a range of targeted therapies following inadequate response to conventional synthetic disease-modifying antirheumatic drugs such as methotrexate. Whereas clinical practice guidelines provide no formal recommendations for initial targeted therapies, the tumor necrosis factor alpha inhibitor (TNFi) class is the prevalent first-line selection based on clinician experience, its safety profile, and/or formulary requirements, while also being the costliest. Most patients do not achieve adequate clinical response with a first-line TNFi, however. A molecular signature response classifier (MSRC) test that assesses RA-related biomarkers can identify patients who are unlikely to achieve adequate response to TNFi-class therapies. OBJECTIVE: To model cost-effectiveness of MSRC-guided, first-line targeted therapy selection compared with current standard care. METHODS: This budget impact analysis used data sourced from August to September 2020. The prevalence of each first-line targeted therapy was obtained using market intelligence from Datamonitor/Informa PLC Rheumatology Dashboard Forecast 2020, and the average first-year cost of treatment for each class was calculated using wholesale acquisition costs from IBM Micromedex RED BOOK Online. Average effectiveness for each class was based on manufacturer-reported ACR50 response rates (American College of Rheumatology adequate response criteria of 50% improvement at 6 months after therapy initiation). The impact of MSRC testing on first therapy selection was predicted based on a third party-generated decision-impact study that analyzed potential alterations in rheumatologist prescribing patterns after receiving MSRC test reports. Sensitivity analysis evaluated potential impacts of variation in first-year medication cost, adherence to MSRC report, and test price on the first-year cost of treatment. Cost for response (first-year therapy cost therapy divided by probability of achieving ACR50) was compared between standard care and MSRC-guided care. RESULTS: The estimated cost for first-year, standard-care treatment was $65,117, with 80% of patients initiating treatment with a TNFi. Cost for achieving ACR50 response was $177,046. After applying MSRC-guided patient stratification and therapy selection, the first-year cost was $56,543, net of test price, with 49.0% of patients initiating with a TNFi. First-year MSRC-guided care cost, including test price, was estimated at $117,103, a 33.9% improvement over standard care. Sensitivity analysis showed a net cost improvement for guided care vs standard care across all scenarios. Patients predicted to be inadequate TNFi responders, when modeled with lower-priced alternatives, were predicted to show increased ACR50 response rates. Those with MSRC test results indicating a first-line TNFi were predicted to show an ACR50 response rate superior to that for any other class. In this model, if implemented clinically, MSRC-guided care might save the US health care system more than $850 million annually and improve ACR50 by up to 31.3%. CONCLUSIONS: Precision medicine using MSRC-guided patient stratification and therapy selection may both decrease cost and improve efficacy of targeted RA therapies. DISCLOSURES: This work was funded in full by Scipher Medicine Corporation, which participated in data analysis and interpretation and drafting, reviewing, and approving the publication. All authors contributed to data analysis and interpretation and publication preparation, maintaining control over the final content. Arnell, Withers, and Connolly-Strong are employees of and have stock ownership in Scipher Medicine Corporation. Bergman has received consulting fees from AbbVie, Gilead, GlaxoSmithKline, Novartis, Pfizer, Regeneron, Sanofi, and Scipher Medicine and owns stock or stock options in Johnson & Johnson. Kenney, Logan, and Lim-Harashima are consultants for Scipher Medicine Corporation. Basu has nothing to disclose.

Cost to Medicare of Delayed Adalimumab Biosimilar Availability.

Launched in 2002, originator adalimumab (Humira) is the top revenue-generating drug in the United States. Between 2016 and 2019, the US Food and Drug Administration approved 5 adalimumab biosimilars, yet none have been marketed owing to patent dispute settlements. We sought to calculate the cost of this delayed entry to Medicare over this period by estimating the difference between reported spending on originator adalimumab and estimated spending on originator and biosimilar adalimumab products assuming timely biosimilar market entry. Estimates of potential biosimilar spending were calculated based on the following evidence-based projections: (i) market capture of 15% for the first biosimilar and 5.5% for successive biosimilars in their first year on the market, and 5% annually thereafter; (ii) price reductions of 3.5% per year and 2.4% per additional biosimilar entry for originator adalimumab; and (iii) price discounts of 25% at launch, 3.4% per year, and 1.7% per additional biosimilar entry for biosimilar adalimumab. Based on these assumptions, had adalimumab biosimilars launched upon approval, estimated non-rebate spending on them would have been $18.3 million in 2016, $225.7 million in 2017, $436.2 million in 2018, and $727.7 million in 2019, whereas estimated non-rebate spending on originator adalimumab would have been $2.33 billion, $2.04 billion, $1.78 billion, and $1.42 billion. Cumulative spending on adalimumab would have thus been $8.98 billion instead of an observed $12.11 billion. Accounting for estimated rebates, total predicted savings would have been $2.19 billion. Reforms for timely biosimilar availability will be critical in ensuring optimal savings for Medicare after biosimilar approval.

Uptake of Biosimilars and Its Economic Implication for the Treatment of Patients with Rheumatoid Arthritis in Korea.

BACKGROUND: We aimed to examine the uptake of infliximab and etanercept biosimilars in patients with rheumatoid arthritis (RA) and its economic implication for healthcare expenditure. METHODS: Using Korean Health Insurance Review and Assessment Service National Patient Samples, we extracted RA patients who used biologic disease modifying anti-rheumatic drugs (bDMARDs) between 2009 and 2018. Descriptive statistics were used to explain the basic features of the data. We calculated the proportion of users of each bDMARD among total patients with bDMARDs half-yearly. We assessed changes in the utilization proportions of bDMARDs including 4 tumor necrosis factor inhibitors (TNFis) and 2 non-TNFis, which have been approved for RA in Korea: etanercept, infliximab, adalimumab, golimumab, tocilizumab, and abatacept, and analyzed the changes in market share of biosimilars among the bDMARDs after their introduction. Overall trends of medical costs for each bDMARD were presented over the 10-year period. RESULTS: Since the introduction of the biosimilar TNFis in 2012, the proportion of their use among bDMARDs steadily increased to 15.8% in 2018. While there has been a gradual increase in the use of biosimilar TNFis, the use of the corresponding originators has been decreasing. The introduction of biosimilar TNFis has resulted in a decrease in the medical costs of patients using either originator or biosimilar TNFis. CONCLUSION: In Korea, the proportional use of biosimilar TNFis has gradually increased since their introduction. The availability of less expensive biosimilar TNFis seems to have brought about a decrease in the medical costs of users of the originators.

Efficacy of a tight-control and treat-to-target strategy in axial spondyloarthritis: results of the open-label, pragmatic, cluster-randomised TICOSPA trial.

OBJECTIVES: To compare the benefits of a tight-control/treat-to-target strategy (TC/T2T) in axial spondyloarthritis (axSpA) with those of usual care (UC). METHODS: Pragmatic, prospective, cluster-randomised, controlled, open, 1-year trial (NCT03043846). 18 centres were randomised (1:1). Patients met Axial Spondylo Arthritis International Society (ASAS) criteria for axSpA, had an Ankylosing Spondylitis Disease Activity Score (ASDAS) ≥2.1, received non-optimal treatment by non-steroidal anti-inflammatory drugs and were biologic-naive. INTERVENTIONS: (1) TC/T2T: visits every 4 weeks and prespecified strategy based on treatment intensification until achieving target (ie, ASDAS <2.1); (2) UC: visits every 12 weeks and treatment at the rheumatologist's discretion. MAIN OUTCOME: Percentage of patients with a ≥30% improvement on the ASAS-Health Index (ASAS-HI). Other efficacy outcomes and adverse events were recorded. A health economic evaluation was performed. STATISTICAL ANALYSIS: Two-level mixed models were used to estimate efficacy outcomes. Cost-effectiveness was assessed by the incremental cost per quality-adjusted life-year (QALY) gained for TC/T2T versus UC. RESULTS: 160 patients were included (80/group). Mean (SD) age was 37.9 (11.0) years and disease duration was 3.7 (6.2) years; 51.2% were men. ASDAS at inclusion was 3.0 (0.7), and ASAS-HI was 8.6 (3.7). ASAS-HI improved by ≥30% in 47.3% of the TC/T2T arm and in 36.1% of those receiving UC (non-significant). All secondary efficacy outcomes were more frequent in the TC/T2T arm, although not all statistically significant. Safety was similar in both arms. From a societal perspective, TC/T2T resulted in an additional 0.04 QALY, and saved €472 compared with UC. CONCLUSION: TC/T2T was not significantly superior to UC for the primary outcome, while many secondary efficacy outcomes favoured it, had a similar safety profile and was favourable from a societal health economic perspective. TRIAL REGISTRATION NUMBER: NCT03043846.

Comparing cost-utility of DMARDs in autoantibody-negative rheumatoid arthritis patients.

OBJECTIVES: To evaluate the 1-year cost-effectiveness between three different initial treatment strategies in autoantibody-negative RA patients, according to 2010 criteria. METHODS: For this analysis we selected all RA patients within the intermediate probability stratum of the treatment in the Rotterdam Early Arthritis Cohort (tREACH) trial. The tREACH had a treat-to-target approach, aiming for low DAS <2.4, and treatment adjustments could occur every 3 months. Initial treatment strategies consisted of MTX 25 mg/week (initial MTX, iMTX), iHCQ 400 mg/day or an oral glucocorticoids tapering scheme without DMARDs (iGCs). Data on quality-adjusted life-years, measured with the European Quality of Life 5-Dimensions 3 Levels (EQ-5D-3L), healthcare and productivity costs were used. RESULTS: Average quality-adjusted life-years (s.d.), for iMTX, iHCQ and iGCs were respectively 0.71 (0.14), 0.73 (0.14) and 0.71 (0.15). The average total costs (s.d.) for iMTX, iHCQ and iGCs were, respectively, €10 832 (14.763), €11 208 (12.801) and €10 502 (11.973). Healthcare costs were mainly determined by biological costs, which were significantly lower in the iHCQ group compared with iGCs (P < 0.05). However, costs due to presenteeism were the highest in the iHCQ group (55%) followed by iMTX (27%) and iGCs (18%). The incremental cost-effectiveness ratios did not differ between treatment strategies. At a willingness-to-pay level of €50 000, the Dutch threshold for reimbursement of medical care, iHCQ had the highest probability (38.7%) of being cost-effective, followed by iGCs (31.1%) and iMTX (30.2%). CONCLUSION: iHCQ had the lowest healthcare and highest productivity costs, resulting in a non-significant incremental cost-effectiveness ratio. However, iHCQ had the highest chance of being cost-effective at the Dutch willingness-to-pay threshold for healthcare reimbursement. Therefore, we believe that iHCQ is a good alternative to iMTX in autoantibody-negative RA patients, but validation is needed. CLINICAL TRIAL REGISTRATION NUMBER: ISRCTN26791028.

Healthcare utilization and economic burden of difficult-to-treat rheumatoid arthritis: a cost-of-illness study.

OBJECTIVES: To determine the impact of difficult-to-treat rheumatoid arthritis (D2T RA) on (costs related to) healthcare utilization, other resource use and work productivity. METHODS: Data regarding healthcare utilization, other resource use and work productivity of 52 D2T (according to the EULAR definition) and 100 non-D2T RA patients were collected via a questionnaire and an electronic patient record review during a study visit. Annual costs were calculated and compared between groups. Multivariable linear regression analysis was performed to assess whether having D2T RA was associated with higher costs. RESULTS: Mean (95% CI) annual total costs were €37 605 (€27 689 - €50 378) for D2T and €19 217 (€15 647 - €22 945) for non-D2T RA patients (P<0.001). D2T RA patients visited their rheumatologist more frequently, were more often admitted to day-care facilities, underwent more laboratory tests and used more drugs (specifically targeted synthetic DMARDs), compared with non-D2T RA patients (P<0.01). In D2T RA patients, the main contributors to total costs were informal help of family and friends (28%), drugs (26%) and loss of work productivity (16%). After adjustment for physical functioning (HAQ), having D2T RA was no longer statistically significantly associated with higher total costs. HAQ was the only independent determinant of higher costs in multivariable analysis. CONCLUSIONS: The economic burden of D2T RA is significantly higher than that of non-D2T RA, indicated by higher healthcare utilization and higher annual total costs. Functional disability is a key determinant of higher costs in RA.

One-year direct costs of biological therapy in rheumatoid arthritis and its predictive factors: data from the Moroccan RBSMR registry.

The aim of the study was to estimate the annual direct costs of biological therapies in rheumatoid arthritis (RA), and to establish possible factors associated with those costs. The main data source was the Moroccan registry of biological therapies in rheumatic diseases (RBSMR Registry). We included patients with available 1-year data. Variables related to socio-economic status, disease and biological therapy were collected. Direct costs included prices of biologics, costs of infusions, and subcutaneous injections. Differences in costs across groups were tested by Mann-Whitney and Kruskal-Wallis tests. Correlations analysis was performed in search of factors associated with high costs. We included 197 rheumatoid arthritis patients. The mean age was 52.3 ± 11 years, with female predominance 86.8%. Receiving one of the following therapies: rituximab (n = 132), tocilizumab (n = 37), or TNF-blockers (n = 28). Median one-year direct costs per patient were €1665 [€1472-€9879]. The total annual direct costs were € 978,494. Rituximab, constituted 25.7% of the total annual budget. TNF-blockers and tocilizumab represented 27.3% and 47% of this overall budget, respectively. Although the costs were not significantly different in terms of gender or level of study, the insurance type significantly affected the cost estimation. A positive correlation was found between the annual direct cost and body mass index (r = 0.15, p = 0.04). In Morocco, a developing country, the annual direct costs of biological therapy are high. Our results may contribute to the development of strategies for better governance of these costs.

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.

Cost-effectiveness analysis of tofacitinib compared with adalimumab and etanercept in the treatment of severe active rheumatoid arthritis; Iranian experience.

BACKGROUND AND OBJECTIVE: This study aimed to evaluate the cost-utility of Tofacitinib (TFC) in patients with severe rheumatoid arthritis (RA) who had not responded well to methotrexate from the Iranian payer's perspective. METHODS: An individual microsimulation Markov model was developed to compare TFC with etanercept (ETN) and Adalimumab (ADA) over a life-time horizon. Treatment efficacy was estimated based on the American College of Rheumatology (ACR) response improvement criteria in 6 months. Changes in the Health Assessment Questionnaire (HAQ) scores were mapped onto utility values to calculate outcomes in terms of QALYs. Direct medical costs were taken from national databases. Uncertainty in model parameters was evaluated by sensitivity analyses. RESULTS: This study demonstrated that TFC was cost-effective in both scenarios. Although TFC was associated with lower QALYs than ETN (6.664 versus 6.876), it was also associated with lower costs over a life-time horizon ($42,565.04 versus $58,696.29). Additionally, TFC was found to be the dominant strategy with a lower cost ($50,299.91 versus $51,550.29) and higher QALYs gained (6.900 versus 6.687) compared to ADA. CONCLUSION: TFC was found to be cost-effective in patients with severe RA who do not respond well to methotrexate compared to ADA, ETN in Iran.

Model to Determine the Cost-Effectiveness of Screening Psoriasis Patients for Psoriatic Arthritis.

OBJECTIVE: Screening psoriasis patients for psoriatic arthritis (PsA) is intended to identify patients at earlier stages of the disease. Early treatment is expected to slow disease progression and delay the need for biologic therapy. Our objective was to determine the cost-effectiveness of screening for PsA in patients with psoriasis in Canada. METHODS: A Markov model was built to estimate the costs and quality-adjusted life years (QALYs) of screening tools for PsA in psoriasis patients. The screening tools included the Toronto Psoriatic Arthritis Screen, Psoriasis Epidemiology Screening Tool, Psoriatic Arthritis Screening and Evaluation, and Early Psoriatic Arthritis Screening Questionnaire (EARP) questionnaires. States of health were defined by disability levels as measured by the Health Assessment Questionnaire. State transitions were modeled based on annual disease progression. Incremental cost-effectiveness ratios and incremental net monetary benefits were estimated. Sensitivity analyses were undertaken to account for parameter uncertainty and to test model assumptions. RESULTS: Screening was cost-effective compared to no screening. The EARP tool had the lowest total cost ($2,000 per patient per year saved compared to no screening) and the highest total QALYs (additional 0.18 per patient compared to no screening). The results were most sensitive to test accuracy and the efficacy of disease-modifying antirheumatic drugs (DMARDs). No screening was cost-effective (at $50,000 per QALY) relative to screening when DMARDs failed to slow disease progression. CONCLUSION: If early therapy with DMARDs delays biologic treatment, implementing screening in patients with psoriasis in Canada is expected to represent a cost savings of $220 million per year and improve the quality of life.

Prevalence of Rheumatoid Arthritis and Drug Dispensing Patterns Among Medicaid and Medicaid-Medicare Dually Eligible Beneficiaries in Puerto Rico.

OBJECTIVE: To estimate the prevalence of rheumatoid arthritis (RA) in Puerto Rico, to describe disease-modifying antirheumatic drug (DMARD) dispensing patterns by prescriber specialty, and to illustrate the impact of RA case definition on the estimated prevalence. METHODS: This study estimated the prevalence of RA in Puerto Rico during 2016 among Medicaid and Medicaid-Medicare dually eligible beneficiaries of the Mi Salud health care plan, a federally funded health insurance program. DMARD dispensing and cost patterns were described and stratified by provider specialty. A sensitivity analysis was conducted to evaluate the effect of RA case definition on estimated prevalence. RESULTS: The prevalence of RA in 2016 was estimated to be 2 cases per 1,000 beneficiaries, with 3 per 1,000 beneficiaries among females, 4.5 times that of males. In total, 44% of beneficiaries received conventional synthetic DMARDs (csDMARDs) only, 32% received biologic or targeted synthetic DMARDs (b/tsDMARDs) only, and 24% received a combination of csDMARDs and b/tsDMARDs. Rheumatologists and a combination of specialties accounted for the highest median number of dispensed DMARDs, with 14 each. A sensitivity analysis revealed that when RA cases with ≥3 medical claims were restricted to having ≥1 DMARD claim, the estimated prevalence changed from 6 to 3 cases per 1,000 beneficiaries. CONCLUSION: The prevalence of RA in Puerto Rico in this study is lower than reported in the mainland US, possibly due to more stringent criteria to define RA. DMARD dispensing and cost patterns are similar to those found in other studies. Claims algorithms that identify RA have higher validity when pharmacy data is included.

Costs of medication use among patients with juvenile idiopathic arthritis in the Dutch healthcare system.

Background: This study aims to quantify medication costs in juvenile idiopathic arthritis (JIA), based on subtype.Research design and methods: This study is a single-center, retrospective analysis of prospective data from electronic medical records of JIA patients, aged 0-18 years between 1 April 2011 and 31 March 2019. Patient characteristics (age, gender, subtype) and medication use were extracted. Medication use and costs were reported as: 1) mean total annual costs; 2) between-patient heterogeneity in these costs; 3) duration of medication use; and, 4) costs over the treatment course.Results: The analysis included 691 patients. Mean total medication costs were €2,103/patient/year, including €1,930/patient/year (91.8%) spent on biologicals. Costs varied considerably between subtypes, with polyarticular rheumatoid-factor positive and systemic JIA patients having the highest mean costs (€5,020/patient/year and €4,790/patient/year, respectively). Mean annual medication costs over the patient's treatment course ranged from <€1,000/year (71.1% of patients) to >€11,000/year (2.5% of patients). Etanercept and adalimumab were the most commonly used biologicals. Cost fluctuations over the treatment course were primarily attributable to biological use.Conclusions: Polyarticular rheumatoid-factor positive and systemic JIA patients had the highest mean total annual medication costs, primarily attributable to biologicals. Costs varied considerably between subtypes, individuals, and over the treatment course.

Cost-utility analysis of treatment options after initial tumor necrosis factor inhibitor therapy discontinuation in patients with rheumatoid arthritis.

BACKGROUND: For patients with rheumatoid arthritis (RA) who discontinued initial treatment with tumor necrosis factor inhibitor (TNFi), 2 approaches are commonly used: cycling to another TNFi or switching to a drug with another mechanism of action. Currently, there is no consensus on which approach to use first. A report from the IBM MarketScan Research administrative claims database showed adalimumab (cycling strategy) and abatacept (switching strategy) were more commonly prescribed after the first TNFi discontinuation. OBJECTIVE: To evaluate the cost-utility of adalimumab versus abatacept in patients with RA whose initial TNFi therapy failed. METHODS: A probabilistic cost-utility microsimulation state-transition model was used. Our target population was commercially insured adults with RA, the time horizon was 10 years, and we used a payer perspective. Patients not responding to adalimumab or abatacept were moved to the next drug in a sequence of 3 and, finally, to conventional synthetic therapy. Incremental cost-utility ratios (2016 USD per quality-adjusted-life-year gained [QALY)] were calculated. Utilities were derived from a formula based on the Health Assessment Questionnaire Disability Index and age-adjusted comorbidity score. RESULTS: Switching to abatacept after the first TNFi showed an incremental cost of just more than $11,300 over 10 years and achieved a QALY benefit of 0.16 compared with adalimumab. The incremental cost-effectiveness ratio was $68,950 per QALY. Scenario analysis produced an incremental cost-effectiveness ratio range of $44,573 per QALY to $148,558 per QALY. Probabilistic sensitivity analysis showed that switching to abatacept after TNFi therapy failure had an 80.6% likelihood of being cost-effective at a willingness-to-pay threshold of $100,000 per QALY. CONCLUSIONS: Switching to abatacept is a cost-effective strategy for patients with RA whose discontinue initial therapy with TNFi. DISCLOSURES: Funding for this project was provided by a Rheumatology Research Foundation Investigator Award (principal investigator: Maria A. Lopez-Olivo). Karpes Matusevich's work was supported by a Doctoral Dissertation Research Award from the University of Texas, School of Public Health Office of Research. Lal reports competing interests outside of the submitted work (employed by Optum). Suarez-Almazor reports competing interests outside of the submitted work (consulting fees from Pfizer, AbbVie, Eli Lilly, Agile Therapeutics, Amag Pharmaceuticals, and Gilead). Chan, Swint, and Cantor have nothing to disclose.

Cost-utility analysis of second-line therapy with rituximab compared to tumour necrosis factor inhibitors in rheumatoid arthritis.

OBJECTIVE: To compare direct costs and treatment utility associated with the second-line therapy with rituximab and tumour necrosis factor inhibitors (TNFis) (adalimumab, etanercept, and infliximab) in patients with Rheumatoid Arthritis (RA) using data from a prospective registry. METHODS: Health Assessment Questionnaire Disability Index (HAQ-DI) scores and RA-related healthcare resource utilization data (biologic agents and visits to rheumatologists) were extracted from a registry (Quebec, Canada) for patients with RA (n = 129) who had to discontinue a first-line TNFi and were treated with rituximab, adalimumab, etanercept, or infliximab as the second-line therapy between January 2007 and May 2016. A decision analytic model followed patients for 1 and 6 years. Treatment utility was measured as quality-adjusted life-years (QALYs) gained, which were calculated from HAQ-DI scores observed over the follow-up time. Quebec 2020 unit costs (Canadian Dollars, $) were used to value healthcare resource consumption. A probabilistic sensitivity analysis was performed with 10,000 Monte Carlo simulations to assess uncertainty around point-estimates of cost-utility. RESULTS: Over 1-year, rituximab and etanercept resulted in the effectiveness of 0.80 QALYs gained at the cost of $14,291and $18,880, respectively, and were dominant (i.e. associated with lower costs and more QALYs gained) compared to adalimumab (0.79 QALYs, $18,825) and infliximab (0.76 QALYs, $20,158). Over 6-years, rituximab (4.42 QALYs, $82,402) was dominant compared to adalimumab (4.30 QALYs, $101,420), etanercept (4.02 QALYs, $99,191), and infliximab (3.71 QALYs, $100,396). In the probabilistic analysis, rituximab was dominant over adalimumab, etanercept, and infliximab with the probability of 0.51, 0.62, and 0.65, respectively. CONCLUSION: Real-world data revealed differences between alternative biologic agents used as the second-line therapy in terms of both treatment costs for the healthcare system and utility of treatment for patients. Therefore, new guidelines on the order of selecting and switching biologic agents should be explored.