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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.

Background: Decentralisation of healthcare budgets and issuance of local guidelines means that the use of biosimilars can vary by region within a particular country, for example between the 21 counties of Sweden., Objectives: This study aimed to analyse the county-level market dynamics of biosimilar and originator infliximab, which are hospital products, and to examine how local policy measures and practices, in addition to national policy, influenced market dynamics., Methods: We first conducted a literature review on (biosimilar) policies in Sweden, then analysed market data provided by IQVIA™ on uptake of originator and biosimilar infliximab within the different counties (Q2 2012 to Q4 2017), including discounts from (tender) contracts. Biosimilar market shares were calculated with volume data (measured as defined daily doses [DDDs]). We then discussed our findings in semi-structured interviews with the national pricing and reimbursement agency, key experts within the county councils of Skåne, Västra Götaland, and Stockholm, and an industry representative., Results: Market shares of biosimilar infliximab vary widely between counties (range 18-96% in 2017). The initial uptake of biosimilar infliximab was slow and variable, with abrupt increments in biosimilar market shares coinciding with expiration of contracts for the originator product. Different approaches taken by counties to achieve a low cost per DDD of infliximab were identified, i.e., a rapid switch to the biosimilar (Skåne), a delayed switch to the biosimilar (Stockholm), or no switch to the biosimilar when a favourable price on the originator product could be obtained (Västra Götaland). Quantitative analysis showed that 59% of the variability in biosimilar market shares could be explained by the relative difference in discounted price between the biosimilar and the originator product. In addition, qualitative analysis indicated the presence of key opinion leaders, local guidelines and initiatives, and whose budget it affects as drivers in the decision-making process., Conclusions: Variations in the market share of biosimilar infliximab between the Swedish counties is largely explained by the discounted price difference between biosimilar and originator product, and counties used different strategies to leverage such biosimilar competition. Additionally, the presence of key opinion leaders, local guidelines and gainsharing arrangements appeared to play a role in infliximab market dynamics in counties.

Objective: The objective was to estimate the cost-effectiveness of TNF-inhibitors for the treatment of rheumatoid arthritis in Swedish clinical practice, both as a first and second biological treatment, with or without the combination of conventional DMARDs. Further sub-group analysis of etanercept treatment was performed., Methods and Materials: Patient level data were obtained from three regions of the Swedish Rheumatology Registers. The dataset contained 2,558 patients who had started TNF-inhibitor treatment, 1,049 with etanercept as their first biological treatment. A total of 819 patients had switched to a second TNF-inhibitor, of which 425 to etanercept. A Markov cohort model was used in which health states of disease severity were classified according to HAQ and DAS28. Disease progression and discontinuation rates of TNF-inhibitors were based on the registry and for the comparator on published literature. Mortality, costs and utilities were based on Swedish data. The main analysis had a societal perspective over 20 years and efficacy was measured in quality-adjusted life-years (QALYs)., Results: TNF-inhibitor treatment was associated with an increase in QALYs and an incremental cost compared to no biological treatment. The cost per QALY gained with the three TNF-inhibitors ranged from euro 50,000 to euro 120,000, with lower estimates for TNF-inhibitors used in combination with MTX and as a first biologic. At a progression of 0.045 for the comparator, most values remain within the accepted range for cost-effectiveness., Conclusions: These results demonstrate that the cost per QALY for TNF-inhibitors was higher than in previous assessments based on registry data and that the results were sensitive to the HAQ progression of the comparator.

Objective: To evaluate the precision of the predictive cost-effectiveness assessment based on a phase 3 clinical trial with infliximab for the treatment of rheumatoid arthritis in Swedish clinical practice., Methods: Three patient cohorts were identified: the patients included in the infliximab trial (ATTRACT), patients initially treated with infliximab from a Swedish registry (STURE), a subset of these registry patients meeting inclusion criteria for the ATTRACT trial was the third patient cohort; two sets of assumptions in relation to the efficacy data were evaluated: "ATTRACT" (efficacy data over the duration of the trial) and "STURE" (effectiveness data over 10 years). In addition, the impact of including the placebo effect for the comparator was evaluated as a basis for the calculation of cost-effectiveness by using a modeling approach. A health economic model was utilized to estimate the cost per quality-adjusted life-year (QALY) gained., Results: The results for the three patient cohorts ranged from cost saving to a cost per QALY gained of €2,400 and €24,900 to €26,000 when the ATTRACT and STURE assumptions were used, respectively. Sensitivity analyses indicated that the inclusion of placebo effect had the largest effect on the results, increasing the cost per QALY gained to approximately €50,000 for all patient cohorts., Conclusions: The treatment effect of infliximab measured in clinical trials and clinical practice results in comparable cost-effectiveness ratios, as calculated by using a modeling approach, whereas the assumptions made in relation to the effectiveness data and the chosen comparator have a large impact on the results. This reinforces the value of early modeling studies based on randomized clinical trial data, but assumptions made need to be carefully assessed., (Copyright © 2013 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.)

Objective: To measure small-area variations in sales per capita of tumour necrosis factor (TNF) inhibitors., Methods: For 2000-2009, sales data on etanercept, infliximab, and adalimumab were retrieved from the Swedish National Corporation of Pharmacies, which keeps data on drugs dispensed in ambulatory care and hospitals. As points of reference, data were retrieved on all drugs, non-biologic treatments for chronic inflammatory disorders (sulfasalazine, methotrexate, azathioprine), and for a biologic used in a different therapeutic area (trastuzumab). As a corollary measure to sales per capita, penetration of biologics in the rheumatoid arthritis (RA) population was calculated using nationwide registers. Small areas were defined as the 21 counties of Sweden., Results: From 2000 to 2009, annual TNF inhibitor sales increased 9-fold from 195 to 1779 million SEK (0.7-5.0% of total drug expenditure). The county variation in sales per capita, initially 6.2-fold (coefficient of variation 42%), decreased to 2.3-fold in 2009 (24%). During the same period, total drug expenditure per capita remained at a 1.2-fold county variation (4-6%). Sales per capita variations of non-biologic treatments against chronic inflammatory diseases ranged from 1.5 to 1.8 (12-16%). For trastuzumab, a 3.2-fold variation (30%) was observed in 2009. At the patient level, there was a 2-fold county variation (from 10% to 21%) in biologic penetration in RA. County-specific sales per capita were associated with mean RA duration (r = -0.52, p = 0.015) and C-reactive protein at treatment initiation (r = -0.49, p = 0.025), while pain was borderline significant (r = -0.43, p = 0.055)., Conclusions: Despite universal access to treatment, substantial but decreasing small-area variations were observed. Although geographic variations are anticipated initially, their persistence calls for investigation of patient equity and treatment appropriateness as counties seem to have different initiation thresholds.

Background: Approximately 14% of Early Breast Cancers, EBCs, and 25% of Metastatic BCs, MBCs, are HER2 positive. There is an effective treatment (trastuzumab) for both EBC (9% increased absolute disease free survival at five years) and MBC (five to nine months' prolonged overall survival). Patients with BC are treated within each of the six different Health Care Regions (HCRs) in Sweden. This aim of this project was to study the introduction and usage of trastuzumab in BC in the six HCRs in Sweden., Materials and Methods: We used official sales data and cancer statistics in the model, and HER2 positive proportions of 25% (prevalent population in year 2000; first year of trastuzumab sales) and 14% and treatment times of 38 weeks and 52 weeks for MBC and EBC, respectively, based on clinical trial data. We used years 2000-2004 for the MBC analyses. In year 2005 data on trastuzumab in EBC were presented, and approval came in year 2006. We studied years 2006-2008 for the use in both EBC and MBC., Results: The percentage trastuzumab treated MBC patients for the entire period in the different HCRs (quarter 4 2000 to end 2004) was: North 57%, Stockholm 48%, South East 40%, South 17%, Uppsala 52%, West 34%. The Sweden average was 40%. The percentage treated patients (MBC and EBC), years 2006-2008 in the different HCRs was: North 68%, Stockholm 75%, South East 43%, South 44%, Uppsala 74%, West 43%. The Sweden average was 59%., Conclusion: The differences in usage of trastuzumab may be explained by variable interpretations of the clinical data and applications in clinical practice, budget issues and differences in coordination, experience and training.

Objectives: The objective of this study was to estimate the cost-effectiveness of infliximab use in patients with rheumatoid arthritis (RA) in Swedish clinical practice, based on patient-level data from the Stockholm TNF-alpha follow-up registry (STURE)., Methods: Real-world patient-level data on infliximab use from the STURE registry were implemented in a Markov cohort model, in which health states of functional status were classified according to the Health Assessment Questionnaire Disability Index (HAQ-five categories) and twenty-eight joint count Disease Activity Score (DAS28). The transition probabilities between HAQ and DAS28 states during treatment, as well as discontinuation rates were modeled based on data from the registry for patients using infliximab as their first-line biological treatment. The transition probabilities in the comparator arm, that is, disease progression without biologic treatment, as well as mortality rates, costs, and utilities were based on published literature. The analysis had a societal cost perspective., Results: Infliximab was associated with an incremental gain in quality-adjusted life-years of 1.02 and an incremental cost of 23,264 euros per patient compared with progression without biologic treatment, producing an incremental cost-effectiveness ratio (ICER) of 22,830 euros (SEK211,136 or US$31,230). Sensitivity analyses of input parameters and model assumptions produced ICERs in the range from 18,000 euros to 47,000 euros., Conclusions: Results from base-case and sensitivity analyses fell well below established benchmarks for cost-effectiveness in Sweden. The results, therefore, indicated that infliximab treatment for RA has provided good societal value for money in Swedish clinical practice, compared with a scenario of no biological treatment.

Objectives: The aim of this study was to estimate the cost-effectiveness of rituximab in patients not responding adequately to the first tumor necrosis factor (TNF) inhibitor using a model constructed to predict resource consumption and health outcomes in a population-based registry of biological treatments in Southern Sweden (SSATG)., Methods: The model was developed as a discrete event simulation model, using SSATG data for the years 1999-2007. The data set included 1,903 patients with complete data on treatments (up to three treatment lines), functional capacity (HAQ), disease activity (DAS28), and utility (EQ-5D). Resource consumption was based on a regular population-based survey of patients in Southern Sweden. Rituximab was incorporated as second line treatment, using effectiveness data for the active group (N = 311) in a clinical trial comparing rituximab to placebo (REFLEX). It is thus compared to the mix of second line biologics used in SSATG. The analysis starts after failure of the first TNF inhibitor. Results are reported as costs (2008 euro) per quality-adjusted life-year (QALY; both discounted 3 percent), for the societal perspective in Sweden., Results: Total costs in the rituximab strategy are estimated at 401,100 euro compared with 403,000 euro in the TNF-inhibitor arm. Total QALYs are 5.98 and 5.78, respectively. The findings were found to be robust in extensive sensitivity analysis., Conclusions: In our model, a strategy where rituximab is used as second line treatment after failure of the first TNF inhibitor provides a small saving (essentially due to the lower price of rituximab) and a QALY gain (due to better effect than the mix of second line TNF inhibitors).

Objective: To estimate the cost-effectiveness of a new treatment (natalizumab) for multiple sclerosis (MS) compared with current standard therapy with disease-modifying drugs (DMDs) in Sweden., Methods: A Markov model was constructed to illustrate disease progression based on functional disability (the Expanded Disability Status Scale (EDSS)). The effectiveness of natalizumab was based on a 2-year clinical trial in 942 patients (AFFIRM). The effectiveness of current DMDs was estimated from a matched sample of 512 patients in the Stockholm MS registry. Patients withdrawing from treatment were assumed to follow the disease course of 824 patients with relapsing-remitting disease at onset in the Ontario natural history cohort. Costs and utilities are based on a recent observational study in 1339 patients. All data sets were available at the patient level. Main results are presented from the societal perspective, over a 20-year time frame, in 2005 Euros (euro1 = 9.25 SEK)., Results: In the base case, treatment with natalizumab was less expensive and more effective than treatment with current DMDs. When only healthcare costs were considered, the cost per quality-adjusted life year gained with natalizumab was euro38 145. Results are sensitive only to the time horizon of the analysis and assumptions about effectiveness of natalizumab beyond the trial., Conclusions: This cost-effectiveness analysis used registry data, cohort and observational studies to extrapolate the efficacy findings of natalizumab from the AFFIRM clinical trial to measure effectiveness in clinical practice. The analysis results suggest that for the population considered, natalizumab provides an additional health benefit at a similar cost to current DMDs from a societal perspective.

Background: Trastuzumab is a monoclonal antibody that together with chemotherapy significantly improves time to progression and overall survival for metastatic breast cancer patients with tumours overexpressing HER2. The aim of this study was to analyse the cost-effectiveness of HER2 testing and trastuzumab in combination with chemotherapy compared with chemotherapy alone from a societal perspective in a Swedish setting., Material and Methods: We used a Markov state transition model to simulate HER2 testing and subsequent treatment in a hypothetical cohort of 65 year old metastatic breast cancer patients. Outcomes included life-time costs, quality adjusted life years (QALY), and cost per QALY gained. Five different testing and treatment strategies were evaluated., Results: We estimated the cost per QALY gained to be about 485,000 SEK for the strategy of IHC testing for all patients, with FISH confirmation of 2+ and 3+, and trastuzumab and chemotherapy treatment for FISH positive patients. For the strategy of FISH testing for all patients, with trastuzumab and chemotherapy for FISH positive patients, we estimated the cost per QALY gained to about 561,000 SEK. The remaining testing and treatment strategies were dominated. Results were sensitive to changes in utilities, the risk of breast cancer related death, and test characteristics., Conclusion: Our analysis indicate that FISH testing for all patients with trastuzumab and chemotherapy treatment for FISH positive patients is a cost-effective treatment option from a societal perspective.

Introduction: Rituximab has significantly improved the prognosis for patients with both indolent and aggressive non-Hodgkin's lymphoma. An economic evaluation was carried out to assess the cost-effectiveness in Sweden of rituximab as maintenance therapy for patients with follicular lymphoma in remission after second line therapy., Materials and Methods: The incremental cost and effectiveness of rituximab maintenance therapy versus observation were evaluated in a health-state transition model. Primary effect measures were quality-adjusted life-years (QALY) and life-years gained (LYG). Model state transitions were calculated based on progression-free and overall survival data from the EORTC20981 trial. The analysis was made from the perspective of the healthcare provider, including direct medical costs presented in euro, 2007 value. Effects and costs were discounted at a 3% annual rate. The stability of the base case results were tested in one-way and probabilistic sensitivity analyses., Results: The evaluation assessed rituximab maintenance therapy to be associated with an incremental cost per QALY gained of euro 12,600 and an incremental cost per LYG of euro 11,200. The average discounted life expectancy for patients on rituximab maintenance was 1.0 year longer than for patients on observation (5.96 vs. 4.94 years). Rituximab maintenance was associated with an additional 0.9 QALY, and total costs per patient were euro 11,500 higher in the treatment arm, compared to observation., Discussion: The results indicate that rituximab maintenance treatment after successful induction therapy for patients with relapsed/refractory follicular lymphoma in Sweden is cost-effective compared to observation.

Background: Severe allergic asthma patients may not be controlled even with guideline recommended care, including inhaled corticosteroids, long-acting beta-2 agonists, theophylline, oral steroids and anti-leukotrienes. They experience exacerbations requiring intensive healthcare use and which may be fatal. Omalizumab, a new monoclonal antibody for use in IgE-mediated allergic diseases, reduces exacerbations and daily symptoms in this patient population. The aim of this study is to estimate the cost effectiveness of adding omalizumab to optimized standard therapy (ST) in patients with severe persistent IgE-mediated (allergic) asthma., Methods: A Markov model comparing lifelong ST with a treatment period of omalizumab add-on therapy followed by ST, was developed based on efficacy data from the INNOVATE trial (28 weeks, N = 419) and Swedish life table and cost data. This model assumes that patients are at risk of having an exacerbation every 2 weeks and are at risk of dying from a clinically significant severe asthma exacerbation. Patients in a steady-state of having no exacerbations are defined to be in an 'optimized asthma control' state. Resource use data and utilities were obtained from INNOVATE and from a UK observational study. Costs from a societal perspective include estimates for drugs, routine care, exacerbations and costs in added years of life; benefits are expressed in QALYs. The response to omalizumab was evaluated after 16 weeks of trial, and non-responders stopped taking omalizumab for the remaining time., Results: Total lifetime discounted costs and QALYs on ST were 52,702 euros and 11.60. Omalizumab add-on therapy cost an additional 42,754 euros for 0.76 additional QALYs, resulting in an incremental cost-effectiveness ratio of 56,091 euros. A probabilistic sensitivity analysis indicates that the 95% CI around the ICER is [31,328 euros; 120,552 euros]. One-way analyses indicate that the results are sensitive to the exacerbation-related mortality rate, the time horizon and the discount rates., Conclusions: Based on the model and the assumptions used, our results suggest that omalizumab provides cost offsets, improves quality of life and may have an attractive ICER in treating the severe allergic asthma population.

Background: Societal decision makers increasingly emphasise their need for evidence based economic analyses to make reimbursement decisions., Objective: To analyse the cost utility of adalimumab, on both incremental cost and incremental quality adjusted life years (QALYs), versus traditional disease modifying antirheumatic drugs and the other tumour necrosis factor (TNF) antagonists suitable for submission to the Swedish LFN (Pharmaceutical Benefit Board)., Methods: Swedish unit costs and treatment guidelines from a lifetime perspective were implemented. A mathematical model, incorporating data from seven trials, simulated the experiences of 10 000 hypothetical patients with moderate to severe rheumatoid arthritis (RA). The primary outcome measure-QALYs-was derived from utility values calculated from a relationship between the Health Assessment Questionnaire (HAQ) Disability Index (DI) and Health Utility Index-III (HUI-3) from adalimumab trial results. The model followed the progression of HAQ-DI through a number of treatments in a sequence accounting for mortality, drug and monitoring costs, and other direct costs., Results: When using ACR50 as a response threshold for determining successful treatment, adalimumab plus methotrexate showed the greatest number of QALYs gained (2.3 from one study and 2.1 from the pooled results of two trials). The etanercept plus methotrexate strategy yielded QALY gains similar to the pooled adalimumab results. Except for the infliximab strategy, the costs results were between 35 000 and 42 000, a range normally considered cost effective in other European countries., Conclusion: Adalimumab appears to be cost effective for the treatment of moderate to severe RA. The results suggest that adalimumab is at least as cost effective as other TNF antagonists.

Objectives: To evaluate costs, benefits, and cost effectiveness of tumour necrosis factor inhibitor treatment over one year in routine clinical practice., Materials and Methods: At four rheumatology units in southern Sweden treatment of 160 consecutive patients with RA was started with either etanercept or infliximab. The economic analysis was based on 116 patients with complete data who received treatment for at least one year. Details on drug treatment, functional capacity, disease activity, and laboratory values were available during the entire treatment. Information on resource use and QoL was collected at baseline and throughout the first year. The cost effectiveness analysis was based on changes in outcome and costs compared with the year before treatment. Cost per quality adjusted life year (QALY) gained was calculated for the entire sample and for patients with different levels of functional disability., Results: During the first treatment year direct costs were reduced by 40%, but indirect costs did not change substantially. Patients' QoL improved on treatment-utility increased from an average of 0.28 to 0.65. Assuming that improvement occurred after three months' treatment, the cost per QALY gained is estimated as euro;43 500. If it occurs after six weeks, in parallel with clinical measures, the cost per QALY is euro;36 900. Sensitivity analysis, including all 160 patients, gave an estimated cost per QALY of euro;53 600. The cost per QALY increases for patient groups with less severe disease., Conclusion: For this patient group, cost effectiveness ratios are within the generally accepted threshold of euro;50 000, but need to be confirmed with larger samples.