The Burden of Rheumatoid Arthritis (RA) and Patient Access to Treatment by prof. Bengt Jönsson, DR. Gisela Kobelt and PROF. Josef Smolen summary of key findings
Table of contents Introduction Introduction 3 What is Rheumatoid Arthritis? 4 How can RA be treated? 5 Burden and cost of RA 6 Uptake of RA drugs 8 Patient access to RA treatment 10 Cost-effectiveness of RA treatment 12 Conclusion 13 About the Authors 14 Rheumatoid Arthritis (RA) is one of the most common autoimmune diseases and a leading cause of chronic pain affecting over 3 million people in Europe alone. This disease has a large medical and economic impact, affecting people as they reach the peak of their careers, forcing them out of work and costing European economies dearly through lost productivity, resulting in lower incomes and higher public expenditures for disability benefits. Despite this, the disease still has a relatively low public profile. In light of the important advances in the management of RA in recent years, an inter-disciplinary research team of health economists and rheumatologists led by Prof. Bengt Jönsson (Stockholm School of Economics), Dr. Gisela Kobelt (University of Lund) and Prof. Josef Smolen (Medical University, Vienna) conducted a comprehensive study of the burden and cost of RA in Europe, North America, Australia and South Africa and examined the level of patient access to new RA therapies. The report seeks to: Establish and compare the impact of RA on patients quality of life; Describe medical advances in the treatment of RA; Analyse differences in patient access to new RA drugs among Member States; Examine the causes of differences in patient access to new RA drugs; Determine the long-term costeffectiveness of new RA drugs in relation to the overall cost of the disease. The full report was published in January 2008 as a supplement to The European Journal of Health Economics (Springer Verlag). The following document provides a summary of the report s key findings. With the report s findings, the authors hope to contribute to an informed and constructive debate on how the burden and cost of RA can be reduced and to foster concrete policy actions by national and European authorities to tackle this public health issue. Acknowledgement: The report was supported by an unrestricted grant from F. Hoffmann La-Roche Ltd. 2 3
What is Rheumatoid Arthritis? How can RA be treated? Rheumatoid arthritis (RA) is a chronic, inflammatory autoimmune disease that causes the immune system to attack the joints, leading to bone and cartilage destruction. It is a disabling and painful inflammatory condition which can lead to substantial loss of mobility due to joint destruction, often ending in the patient being wheel-chair bound or even bedridden. If left untreated, RA causes irreversible joint damage within three years of disease onset and up to 50% of RA patients are no longer able to work 10 years after onset. There have been important innovations in the treatment of RA over the past 10 years, particularly with the development of new disease-modifying biologic drugs. This new generation of drugs targets the pro-inflammatory cells overproduced in RA patients. Older anti-rheumatic drugs, many of which date back to the 1940s/50s, can slow down the inevitable progression of the disease but in most patients are unable to stop progression altogether. The majority of patients treated with these drugs in clinical trials show less than 50% improvement in signs and symptoms. the productivity and continued labour force participation of RA patients. One key barrier to early diagnosis is the time it takes until RA patients are seen by a rheumatologist. Once diagnosis has occurred, it is important to quickly find the appropriate treatment, i.e. the treatment that is most effective for the individual patient. It appears that making rapid decisions (i.e. within 3-6 months) on whether to continue a particular treatment or change to a new treatment improves patients chances of receiving the most effective treatment. Figure 1: X-Ray of a hand affected by RA As a result of recent medical advances, a state of remission, the reversal of disability and halt in the progression of joint damage have become realistic treatment goals in RA. One in five patients experiences remission today, and even better results are expected with the arrival of new therapies. Diagnosing and effectively treating RA in its early stages has been shown to confer important advantages. It can help delay or even halt progression of joint damage, thereby reducing physical disability. This, in turn, has important effects with respect to New biologic drugs can reduce disease progression and can even lead to an improvement of inflammation-induced disability Diagnosing and effectively treating RA early leads to improvements in patients quality of life Assessing treatment response and changing treatment early may be a viable therapeutic strategy for the future 4 5
Burden and cost of RA There are approximately 6.7 million RA patients in the 36 countries studied in the report, of which approximately 3 million are in Europe. The disease is usually more common and severe in Northern and Central Europe than in South European countries. RA has a large impact on patients quality of life. Within chronic diseases, RA has one of the worst utility (quality of life) scores, similar to that of Multiple Sclerosis. RA is also associated with increased mortality, mostly due to the cardiovascular consequences of chronic inflammation. Deaths from RA are highest in Denmark, Finland, Norway, and Sweden. This may be explained by the higher prevalence of the disease and an older population in Northern countries. RA is a costly disease. The total annual economic impact of RA is estimated at E42 billion in Western Europe and E3.4 billion in Eastern Europe (2006 figures). The mean annual cost of RA per patient is estimated at E13,500 but can rise as high as E40,000 per year (in France) by the later stages of the disease. The report provides a clear cost structure for RA. As shown in Figure 2, 65% of costs linked to RA treatment occur outside the health care sector, in the form of indirect costs and informal care costs, while RA drugs, despite a tenfold increase in cost over the last ten years, still account for only 14% of the disease s overall cost. The new RA drugs must therefore be considered in relation to their positive health impact and the potential savings from reductions in the long term cost of caring for an RA patient. Lost production due to decreased work capacity is the biggest cost driver of RA. Up to 50% of RA patients are forced to leave the workforce within ten years of disease onset, requiring disability pensions and extra care. As shown in Figure 3, only 15% of RA patients in France below 60 years of age (the official retirement age) with severe functional disability (HAQ>2) remain in the workforce. 60 % 50 % RA costs Europe approximately 45.4 billion a year Up to 50% of RA patients have to leave the workforce and obtain a disability pension within 10 years after disease onset Costs outside the health care sector such as lost production, informal care, and nonmedical costs represent nearly two thirds (65%) of all RArelated costs 60 % 50 % % < 60 years % Working 40 % 40 % 19% 21% 30 % 30 % Medical costs 20 % 20 % 14% Drug Non-medical costs Indirect costs Informal care costs 10 % 0 % < 0.5 0.5 < 1.0 1.0 < 1.5 1.5 < 2.0 2.0 < 2.5 >=2.5 10 % 0 % 32% 14% Disease Severity (HAQ) Figure 2: Overview of RA-related costs Figure 3: Workforce participation of RA patients in France 6 Source: Kobelt, G., Richard, B., Peeters, P., Sany, J.: Costs and quality of life of patients with RA in France. ACR 2006, Bone Joint Spine 75(7),(2008). 7
Uptake of RA drugs There are considerable differences in the uptake of new RA drugs between the countries included in the study. As shown by Figure 4, the uptake of biologic RA drugs (in this case, TNF inhibitors) is about three times higher in the US than in Western Europe and Canada. 1 There is very limited use of biologic drugs in Eastern and Central European countries. The Czech Republic has the highest uptake in Eastern Europe (E10) 2 but this is still only a quarter of the Western European average. The lower income and healthcare expenditures in these countries are a probable explanation for this. There are also large disparities in uptake within Western Europe. Norway and Sweden have the highest uptake, 1 To calculate the uptake of diseasemodifying biologic drugs in the different markets, the authors started by analysing overall sales data for Tumor Necrosis Factor (TNF) inhibitors (at manufacturers prices) to get a broad picture. They then complimented and verified these results with other data from independent sources for greater accuracy. Around 70% of total sales are attributed to RA. 2 E10 represents Central and Eastern European countries, which all have a low GDP per capital and thus low health care expenditures per capita compared with E13. ahead of a number of smaller countries such as Belgium, Denmark, Finland, the Netherlands, and Switzerland. Among the large EU Member States, France, Spain and the UK are approximately at the E13 3 average while Germany s and Italy s uptake is below average. Drug prices do not seem to be the major cause of differences in the uptake of biologic RA drugs. For instance, both Germany and Italy have below average uptake of new RA therapies despite the fact that Germany has one of the highest and Italy one of the lowest prices. 3 E13 is a construct from the old EU15 countries. No data or incomplete data were available for Portugal, Ireland, Greece and Luxembourg so that these countries were excluded and replaced by Norway and Switzerland. This group represents countries with a high GDP per capita and hence high health care expenditures. 400,000 350,000 300,000 250,000 200,000 150,000 100,000 50,000 0 2000 Q1 2000 Q2 Canada E13 EU10 United States of America 2000 Q3 2000 Q4 2001 Q1 2001 Q2 2001 Q3 2001 Q4 2002 Q1 2002 Q2 2002 Q3 2002 Q4 2003 Q1 2003 Q2 2003 Q3 2003 Q4 Year Quarter Figure 4: United States, Canada, E13 and E10: Sales of TNF inhibitors per 100,000 population There are large differences in patient access to biologic RA drugs between Member States The EU is lagging behind the US in the uptake of biologic RA drugs There is very limited use of biologic RA drugs in Eastern and Central European countries Differences in drug prices do not seem to be the major cause of differences in the uptake of biologic RA drugs 2004 Q1 2004 Q2 2004 Q3 2004 Q4 2005 Q1 2005 Q2 2005 Q3 2005 Q4 2006 Q1 2006 Q2 2006 Q3 2006 Q4 8 9
Patient access to RA treatment Czech Republic Slovakia Belgium Italy Slovenia France Hungary Greece Spain Portugal Netherlands Finland Sweden Switzerland Norway Ireland US UK Germany 0 100 200 300 400 500 600 Figure 5: Average time delay between marketing authorization and market access (hospital and retail combined). Note: Germany, United Kingdom and United States are at 0 as products are in principle reimbursed at launch without specific negotiations or decisions. Adapted from: Patients W.A.I.T. Indicator (2007), Phase Report, IMS Management Consulting Economic factors play an important role in determining access to biologic RA drugs. Countries with low GDP and health care expenditures per capita tend to have a lower uptake. However, health care budgets or the cost of the drugs are not the only determinants governing patients access to the most effective treatment. The access to a rheumatologist, and hence early diagnosis and treatment, differ substantially across the EU. It is estimated that there is one rheumatologist per 25,000 people in France and 1/50,000 in the US, but only 1/150,000 in the UK and 1/200,000 in Germany. This directly affects patients ability to receive rapid treatment changes according to their response to different drugs, further hampering their quick access to effective treatment. The authorisation process for new drugs and governments attitude to reimbursement are key factors determining patient access. The US, UK and Germany have the fastest time from scientific market authorisation to market access of new drugs of all the countries included in the study, while the Czech Republic is the slowest (the process lasts for more than a year). Patients in Germany and the UK can therefore access the newest treatment significantly faster than those in the Czech Republic and other countries with lengthy price and reimbursement negotiations. Drug approval procedures and reimbursement decisions are not the only hurdles however. Health Technology Assessments (HTAs), including cost-effectiveness evaluations are gaining increasing importance for the allocation of healthcare resources, and have a strong influence on the uptake of RA treatments. Government reimbursement policies are often determined by influential HTAs. The UK and Denmark, whose HTA agencies use a strict healthcare cost perspective, have lower uptake of biologics than Norway, Sweden and the Netherlands where HTA has a stronger focus on the societal perspective. This seems to indicate that countries with a comprehensive assessment of the value and costeffectiveness of biologic drugs for different patient groups allow a more extensive use of (and thus better access to) them. Economic factors are an important, but not the only factor in determining patient access to new drugs Drug approval processes and reimbursement decisions based on Health Technology Assessments (HTAs) are two factors affecting patient access to up-to-date treatments for RA There are also other barriers to early diagnosis and access to treatment such as limited access to specialists A comprehensive approach to economic evaluation and HTA appears often to lead to better access to new drugs 10 11
Cost-effectiveness of RA treatment Conclusion Diagnosing and effectively treating RA in its early stages brings important advantages, and can lead to a delay in disease progression and irreversible joint destruction. Disease progression is associated with deteriorating quality of life and increasing costs, both direct and indirect: in particular, costs outside the formal health care services (productivity losses due to sick leave or invalidity, costs for professional help at home, as well as help and care from family members). Thus, the early clinical success of drugs can be expected to improve patients quality of life during all stages of the disease, but can also prevent patients from having to take time off work or leave the workforce early and ultimately delay or even prevent the late (and most expensive) phases of the disease. Cost-effectiveness studies of these therapies must therefore be carried out from the perspective of society as a whole, where all costs including productivity losses are accounted for in the long term. The full effect of the biological drugs cannot yet be observed directly, and economic models have to be used to estimate the long-term treatment cost versus potential cost savings and quality of life gains. As the disease progresses, patients quality of life deteriorates while direct and particularly indirect costs increase considerably The early clinical success of drugs can be expected to improve patients quality of life but also prevent them from having to leave the workforce early Cost-effectiveness studies of these therapies must be carried out from the perspective of society as a whole, looking at long-term effects and including productivity losses and all other costs As one of the most common autoimmune diseases, RA exerts a large medical and economic impact on both individual patients and society as a whole. With recent medical advances in the treatment of RA, there is fresh hope for people affected by the disease: medical data have shown that early treatment with biologic RA drugs reduces inflammation and can prevent or reduce the speed of joint damage and hence the progression of affected individuals to disability. However, these advances come at a price which makes it difficult for individual patients to pay for the treatment themselves. Third party payment, or reimbursement, is thus key to treatment access. However, third party payers also face a budget constraint and have to prioritise. This is most obvious when looking at the very limited use of biologics in those EU countries with the lowest incomes. The establishment of a common market with a common price for all countries has, at least in the short run, created an economic hurdle compared to a situation where manufacturers can use price discrimination to increase sales as well as access. This said, it is clear that the income level is only one factor. There are also significant variations between countries with similar incomes. The total annual economic impact of RA is estimated at 42 billion in Western Europe and 3.4 billion in Eastern Europe (2006 figures). Up to two-thirds (65%) of costs for RA patients such as productivity losses, patient out-of-pocket costs and informal care occur outside the health care sector. The prime cost driver of RA comes from patients having to leave the workforce early due to the disease: up to 50% of those living with RA are forced to give up work and apply for a disability pension within ten years of disease onset. The findings underline that health policy and resource allocation in RA must be based on a societal perspective and not just a health care perspective. In particular, the costs of biologic RA drugs must be viewed within the overall cost of the disease and the benefit of these drugs over the long term, that is, in relation to their positive health impact and the savings that could eventually result from this. Patient access to good care and treatment, including thorough follow-up and access to innovative drug therapies where indicated, are critical elements that will benefit all of society, reducing the burden and cost of RA. 12 13
About the Authors Prof. Bengt Jönsson Since 1991: Professor of Health Economics, Stockholm School of Economics Member of the Scientific Advisory Board, National Board of Health and Welfare, Sweden. Since 1991: Member of the Board, IHE, The Swedish Institute for Health Economics Associate Editor for Journal of Health Economics. Member of the Editorial Board, Pharmaco-Economics Member of the Editorial Board, Health Economics in Prevention Care, The European Journal of Health Economics. Consultant, UNIDO, 1983. Report on global scenarios for pharmaceutical sales 1990 and 2000. Author of over 200 publications in the fields of rheumatology and immunology. Dr. Gisela Kobelt Managing Director of European Health Economics France Since 2007: visiting Professor at the Department of Orthopedics/ Rheumatology at the University of Lund in Sweden 1998-2002: Stockholm School of Economics Until 1998: Vice-President of Corporate Health Economics, Pharmacia & Upjohn Corporate Management Center Stockholm/ London Until 1998: Creation of health economics departments at Sandoz (now Novartis) Education: Master s degree from the University of Strasbourg (France), MBA from the Institute for Management Development (IMD/IMEDE) in Lausanne (Switzerland), and a PhD in health economics from the Karolinska Institute in Stockholm (Sweden) Author of over 50 scientific publications in the field of health economics, with a particular focus on autoimmune diseases, and a number of disease-specific books Prof. Josef S. Smolen Professor of Internal Medicine and Chairman of the Department of Rheumatology at the Vienna General Hospital, Medical University of Vienna (Austria). Chairman of the Centre for Rheumatic Diseases in Hietzing Hospital, Vienna Former President of the European League Against Rheumatism (EULAR) Major research interests: pathogenesis of rheumatic diseases, particularly rheumatoid arthritis and systemic lupus erythematosus, and new therapeutic approaches to the treatment of rheumatic diseases Author of over 200 publications in the field of rheumatology and immunology Member of several editorial boards of international rheumatology publications 14 15