Cost-utility analysis of Interferon Beta-1b in the treatment of different types of Multiple Sclerosis

Background Economic evaluation of treatments in multiple sclerosis (MS) presents a challenge. The disease affects a number of different body functions and leads to severe disability over time, without however a strong effect on mortality. At onset, the majority of patients will have relapsing-remitting disease (RRMS) and will then convert to secondary-progressive disease (SPMS) overtime. However, the course of the disease is unpredictable, and the conversion to SPMS can take place at different times since onset and at different levels of disability for different patients. Relapses appear to occur with the same frequency at all levels of disability, but will diminish over time. The effectiveness of treatments can be measured in different ways such as disease activity, the number and the severity of relapses or the progression of functional disability, regardless of the type of MS. However, improvements in outcome achieved over a short term may have an effect on the disease in the longer term, and effectiveness data from clinical trials must therefore be extrapolated to the longer term, using modelling techniques. This requires good epidemiological data on the natural course of the disease, where disease progression is expressed with the same measures as in the clinical trials. Also to perform economic evaluations, a global outcome measure is required to capture the impact of treatments on the disease and the most frequently used such measure is quality-adjusted life years (QALYs). However, for QALYs to be used in cost-effectiveness analysis of MS, they must be related to a measure of the disease and disease progression. The Expanded Disability Status Scale (EDSS) provides a good measure of the disease and has been widely used in epidemiological studies and clinical trials, in all types of MS. Lastly, detailed economic data that can be related to the different levels of disability (EDSS) are required. Objective We have earlier proposed a basic framework for cost-effectiveness modelling in MS, and the original model has been updated, as new data have become available. The current study proposes a further development of the modelling technique and estimates the cost-effectiveness of treatment with interferon b-1b (IFNB-1b) in a defined patient population with active disease, both RRMS and SPMS, from a societal perspective in Sweden. Methods The framework of the earlier Markov model is used, where states are defined according to EDSS. Transition probabilities for the first years in the model are calculated from clinical trial data, and for the extrapolation from a large epidemiological database on the natural history of MS. In view of the fact that the number of relapses at given levels of disability did not differ between patients with RRMS or SPMS in any of the three datasets used in this analysis, and that conversion from RRMS to SPMS did not occur at well defined levels of disability, we combined data from two large clinical trials in RRMS and SPMS. Patients were selected on whether or not they had active disease at enrolment, defined as an increase in the EDSS by at least 1 point (0.5 points for scores between EDSS 6 and 7) or at least 2 relapses in the preceding 2 years. This allows simulating treatment start at any stage and for any type of the disease and estimating long-term consequences within the same model. The combination of the two types of MS is further supported by the fact that it has been shown in 3 observational studies that costs and quality of life at given EDSS levels are not different for patients with different types of the disease. Transition probabilities between the Markov states are estimated for both the clinical trial and the natural history cohorts using an ordered probit model. Transitions thus depend on several factors, including what state a patient is in, whether or not she/he has a relapse, age, age at onset of the disease, time since onset of the disease, age at treatment start. The base case simulations use mean costs and mean utilities in each state from a large observational study in Sweden. However, the model allows calculating acceptability curves, i.e. the probability with which the cost effectiveness ratio of a treatment scenario is below given levels of willingness-to-pay for a QALY, using the entire distribution of costs and utilities at each EDSS level. Costs and benefits are discounted with 3%. Results The base case assumes treatment with IFNB-1b during 36 months, with no further effect when treatment is stopped, and includes both patients with active RRMS and SPMS. Sensitivity analysis is presented for treatment during 54 months. The annual cost of IFNB-1b treatment was 102 587 SEK plus 1600 SEK for special monitoring, and was adjusted for compliance in the clinical trial. In the base-case treatment adds 13 000 to costs over 10 years, and the cost per QALY gained is 71 400 SEK. When the time horizon is increased to 15-25 years, treatment dominates no treatment (higher utility and lower cost). With treatment during 54 months, the cost per QALY is 353 800 SEK, all costs included. When treatment is started early, the cost-effectiveness ratio is higher, e.g. 643 100 SEK in state 2, as patients in these states progress only very slowly. In the net benefit approach, there is a 80% probability that the treatment initiated in states 3 or 4 (EDSS 4.0-5.5) is cost-effective, if the willingness to pay for a QALY is 400 000 to 600 000 SEK. At that level of willingness to pay, the probability in state 2 is 45%. Conclusions With this new model, which combines active RRMS and SPMS, the effect of early treatment on the long-term outcome can be estimated for the first time using patient-level clinical data for RRMS and SPMS, as well as natural history data. The combination of the two types of MS into one model is supported by the finding that, at given levels of EDSS, there was no difference in the number of annual relapses in the three clinical datasets used, nor in the mean cost and mean utilities in the observational study. The model is more flexible than previous models, as it includes individual patient demographics and the entire distribution of costs and utilities in the different states. It thus represents a valuable tool to estimate the cost-effectiveness of treating different patient groups with IFNB-1b.MS; Cost-effectiveness

Costs and Quality of Life in Multiple Sclerosis. A Cross-Sectional Observational Study in Germany

We performed a cross-sectional, “bottom-up” observational study of resource consumption and quality of life of patients with multiple sclerosis (MS) in Germany. Six centers participated in the study. Patients were asked to complete a questionnaire, and a total of 737 patients returned the questionnaire (the answer rate being 66%). The questionnaire provided information on all resource consumption, medical and non-medical, work absence and informal care related to their MS. Simultaneously, medical charts were also abstracted for a sub sample of 202 patients. For this sub sample, disease scores (Expanded Disability Status Scale, EDSS) were available from the study centers. For the remainder, disease scores were assigned using a matrix of disease (mobility) descriptions and EDSS scores. Mean total cost per patient and year was 65,400 DM, adjusted for usage of interferons, which was higher in this sample than the current average usage in Germany. When this cost is extrapolated to an estimated patient population of 120,000, total costs to society are estimated at 7.85 billion DM. Direct costs represented 57.5%, informal care accounted for 12.1% and indirect costs amounted to 42.5%. An estimated 24,800 DM per patient or 38% of total costs are paid for by public payers. Intangible costs were estimated 16,650 DM per patient and year. The mean age of the cohort was 42 years (disease onset 33), the mean utility measured with EQ-5D was 0.552 (0.919 to –0.429), and the mean EDSS score 4.4 (1.0 to 9.5). All costs (direct, informal care, indirect) increased with increasing EDSS scores, while utilities decreased.Keywords: multiple sclerosis; cost-of-illness; quality of life; EDSS; utility

Costs and Quality of Life in Multiple Sclerosis. A Cross-Sectional Observational Study in the UK

Abstract: We performed a cross-sectional, "bottom-up" observational study of resource consumption and quality of life of patients with multiple sclerosis (MS) in the United Kingdom. Three centers participated in the study. Patients received a questionnaire either by mail or during a clinic visit, and a total of 619 patients returned the questionnaire (the answer rate being around 70%). Patients provided information on all resource consumption, medical and non-medical, work absence and informal care related to their MS. Disease scores (Expanded Disability Status Scale, EDSS) were available for a majority of patients from the study centers, and were assigned using a matrix of disease (mobility) descriptions and EDSS scores. Mean total cost per patient and year was 16’717 £. When this cost is extrapolated to an estimated patient population in the UK of 80’000, total costs to society are estimated at 1.34 billion £. Direct costs represented 28%, informal care accounted for 26% and indirect costs amounted to 46%. Of the direct costs, an estimated £ per patient or % of total costs are paid for by the NHS. Intangible costs were estimated at 5000 £ per patient and year. The mean age of the cohort was 44 years (disease onset 34), the mean utility measured with EQ-5D was 0.487 (0.919 to –0.594), and the mean EDSS score 5.1 (1.0 to 9.5). All costs (direct, informal care, indirect) increased with increasing EDSS scores, while utilities decreased.multiple sclerosis; cost-of-illness; quality of life; EDSS; utility

Annual direct medical cost of active systemic lupus erythematosus in five European countries.

OBJECTIVES: To evaluate the annual direct medical cost of managing adult systemic lupus erythematosus (SLE) patients with active autoantibody positive disease in Europe. METHODS: A 2-year, retrospective, multicentre, observational study was conducted in five countries (France, Germany, Italy, Spain and the UK). Data included patients' characteristics, disease activity and severity, flare assessments and health resource use (eg, laboratory tests, medications, specialist visits and hospitalisations). Costs were assessed from the public payers' perspective. Cost predictors were estimated by multivariate regression models. RESULTS: Thirty-one centres enrolled 427 consecutive eligible patients stratified equally by disease severity. At baseline, mean (SD) age was 44.5 (13.8) years, 90.5% were women and mean (SD) SLE duration was 10.7 (8.0) years. The SELENA-SLEDAI (11.2 vs 5.3) and SLICC/ACR index (1.0 vs 0.7) scores were higher in severe patients. Over the study period, patients experienced on average 1.02 (0.71) flares/year. The mean annual direct medical cost was higher in severe compared to non-severe patients ( 4748 vs 2650, p<0.001). Medication costs were 2518 in severe versus 1251 in non-severe patients (p<0.001). Medications represented 53% and 47% of the total cost for severe and non-severe patients, respectively, primarily due to immunosuppressants and biologics. Flares, especially severe flares, were identified as the major cost predictor, with each flare increasing the annual total cost by about 1002 (p<0.001). CONCLUSIONS: The annual direct medical cost of SLE patients in Europe is related to disease severity and flares. Medical treatments were the main cost drivers. Severe flares and major organ involvement were identified as important cost predictors

A review of the value of innovation in inhalers for COPD and asthma

Background: Appropriate use of inhaled therapies for asthma and chronic obstructive pulmonary disease (COPD) is critical to ensuring good patient outcomes, efficient use of healthcare resources and limiting the effects of high-morbidity. The appropriate choice of inhaler and active therapy, incorporating patient preferences, can help improve treatment adherence and long-term outcomes. Despite this, many current inhalers are non-intuitive to use, and require extensive training. Methods: In this review, an expert panel considers the evidence for the use of inhaler devices in management of COPD and asthma. The panel also evaluates the value of innovation in inhaler technologies, which optimise the use of existing molecules from a clinical, economic and societal perspective. Conclusions: The panel conclusion is that there remains a substantial unmet need in inhaler technology and that innovation in inhaler devices can provide real-world health benefits to patients. Furthermore, we recommend that these innovations should be supported by healthcare systems through appropriate pricing and reimbursement mechanisms. Keywords: Asthma; Chronic obstructive pulmonary disease; innovation; patient preference; adherence; patient compliance; metered dose inhaler; dry powder inhaler; medication errors; valu

New insights into the burden and costs of multiple sclerosis in Europe

Background: The current focus in multiple sclerosis (MS) is on early diagnosis and drug intervention, with a view to modifying disease progression. Consequently, healthcare costs have shifted from inpatient care and rehabilitation to outpatient care. Objectives: This European burden of illness study provides data that can be combined with other evidence to assess whether management approaches provide value to society. Methods: A cross-sectional study was conducted in 16 countries. Patients reported on their disease, healthrelated quality of life (HRQoL) and resource consumption. Descriptive analyses were performed by disease severity. Costs are reported from a societal perspective in 2015€ PPP (adjusted for purchasing power parity). Results: The 16,808 participants had a mean age of 51.5 years, and 52% had relapsing–remitting multiple sclerosis (RRMS). Work capacity declined from 82% to 8%, and utility declined from normal population values to less than zero with advancing disease. Mean costs were 22,800€ PPP in mild, 37,100€ PPP in moderate and 57,500€ PPP in severe disease; healthcare accounted for 68%, 47% and 26%, respectively. Fatigue and cognitive difficulties were reported by 95% and 71% of participants, respectively; both had a significant independent effect on utility. Conclusion: Costs and utility were highly correlated with disease severity, but resource consumption was heavily influenced by healthcare systems organisation and availability of services

Health economic issues in rheumatoid arthritis

The objectives of treatment in rheumatoid arthritis (RA) are to reduce temporary symptoms due to inflammatory activity and, more importantly, to preserve function. The introduction of potent disease-modifying anti-rheumatic drugs (DMARDs) in recent years has increased the opportunities for effective treatment. However, these treatments come at a substantially higher cost than traditional DMARDs and therefore compete with other essential interventions for limited resources. They have triggered a debate on whether they represent an efficient use of resources, which patients should be treated, when, and for how long. Cost-effectiveness analysis attempts to estimate the trade-offs involved in these decisions and to provide information that can help in making them. However, in chronic progressive diseases, health gains and any potential associated economic benefits are often most evident in the long term. As a consequence, the impact of new treatments has to be estimated using models that can project available knowledge, such as results from clinical trials or short-term follow-up studies in clinical practice, into the future. These models also allow scenarios to be explored that provide the best value for money, for example by defining subgroups for which treatment is most effective, or criteria that define when treatment should be stopped. Economic evaluation in RA has a long tradition, with the first study performed about 20 years ago. However, with the recent drug introductions, the field has witnessed an explosion of economic studies. Modelling techniques have become more sophisticated to overcome concerns about their validity. At the same time, they may appear less transparent, making it difficult for non-specialists to understand the details. This article, rather than reviewing all published models and comparing them, attempts to illustrate the inputs required for such studies, and the influence that different approaches and datasets can have on the results

Health economic evaluation: why? When? How?

Advances in research and better understanding of the pathophysiology of diseases have resulted in an increase in the number of available health interventions that compete for finite public resources. Explicit choices must therefore be made about funding

Treating to target with etanercept in rheumatoid arthritis: cost-effectiveness of dose reductions when remission is achieved.

Current management of rheumatoid arthritis (RA) focuses on inducing remission as early as possible to avoid lasting joint damage, and maintenance of remission has become important. A 12-month clinical trial in 834 patients with moderate RA investigated whether etanercept 50 mg/wk could be reduced to half dose or discontinued in patients who achieved low disease activity after 36 weeks