Contents:

CHAPTER 1 EXECUTIVE SUMMARY 3 Scope of the analysis 3 Insight into the RA market 5 Legislation overhauling the Medicare program has created, for the first time, a prescription drug benefit to complement existing coverage of medical services. The addition of this prescription drug benefit to Medicare in the 10 year, $400bn overhaul of the US federal health insurance program for those 65 and older will have significant effects on the RA market and treatment practices, in particular in the biologics sector. The advantage Remicade currently enjoys over its rivals as an infusion product reimbursed under Medicare is set to narrow, transforming the dynamics of the biologic DMARDs sector. 6 Disputes over licensing deals have affected both marketed and pipeline RA products, with serious consequences for both licensors and licensees. Celltech and CAT have had licenses for RA products terminated or disputed, affecting these relatively small biotech players’ stability. The need for big pharma to supplement pipelines through in licensing makes it important that larger companies refrain from alienating the biotech sector, so as to avoid jeopardizing future opportunities to conclude much needed licensing agreements with potential biotech partners. 9 The demographics of population and disease, and the realities of the political environment, appear to favor RA as a disease in which patient advocacy groups should possess a powerful lobbying voice. However, the polarization of political issues provides an explanation for why it is not always easy for RA advocacy groups to leverage their demographic advantages in lobbying for resources for RA patients. 11 Key metrics 13 CHAPTER 2 INTRODUCTION AND SCOPE 22 Coverage of the Stakeholder Insight: Rheumatoid Arthritis survey 22 Country treatment trees 23 Supporting data sets 23 Key stakeholder organizations 24 CHAPTER 3 COUNTRY TREATMENT TREES 25 US 27 Japan 31 France 35 Germany 39 Italy 43 Spain 47 UK 51 CHAPTER 4 EPIDEMIOLOGY AND PATIENT SEGMENTATION 55 Disease definition 55 Epidemiology of RA 55 Comorbidities 58 CHAPTER 5 DIAGNOSIS AND TREATMENT OPTIONS 61 Diagnosis and referral 61 Diagnosis 61 Referral 62 Treatment rates 64 Influences on diagnosis and treatment rates 67 Treatment guidelines 69 CHAPTER 6 PRESCRIBING TRENDS AND INFLUENCING FACTORS 72 Prescribing trends 72 Global trends 72 Mild RA 74 Moderate RA 75 Severe RA 75 Traditional NSAIDs and COX-II inhibitors 76 COX-II inhibitors and Japan 78 Traditional and biologic DMARDs 80 Biologic DMARDs and Japan 81 Oral and injectable steroids 82 Changes in therapy 85 Traditional DMARDs versus traditional NSAIDs 85 Drug combinations 87 NSAIDs plus traditional DMARDs 89 NSAIDs plus biologic DMARDs 90 NSAIDs plus traditional DMARDs plus biologic DMARDs 91 Traditional DMARDs plus biologic DMARDs 92 Factors influencing physician decision making 93 Factors influencing physician decision making: traditional DMARDs 96 Methotrexate 98 Plaquenil 99 Sulfasalazine 99 Arava 100 Gold 102 Penicillamine 102 Factors influencing physician decision making: biologic DMARDs 103 Remicade 104 Enbrel 105 Kineret 106 Humira 107 Biologic DMARDs compared 108 Traditional and biologic DMARDs: influences and issues 111 DMARD initiation 111 DMARD switching 112 DMARD combination therapy 114 Methotrexate response 115 Biologic DMARD initiation 116 Biologic DMARD switching and termination 117 Enbrel and methotrexate 119 Biologic DMARD side effects 121 Biologic DMARD safety 122 Biologic DMARD pricing 123 CHAPTER 7 IMPROVING TREATMENT OUTCOMES 125 Treatment outcomes 125 Compliance 126 Unmet needs 129 New product development 133 CHAPTER 8 OTHER STAKEHOLDER INFLUENCES 136 Improving diagnosis and treatment: the roles of stakeholders 136 PCP education 136 Consumer education 138 Patient advocacy groups: influence, impact, perspectives 138 CHAPTER 9 OPINION LEADER AND STAKEHOLDER TRANSCRIPTS 140 Opinion leader interviews: methodology 140 Opinion leader interviews: biographies 140 Professor Allan Gibofsky 140 Professor David Isenberg 141 Professor Philip Mease 141 Professor Gerald Weissmann 141 Opinion leader interviews: questions 143 Opinion leader interviews: answers 144 APPENDIX A 167 Bibliography 167 Physician research methodology 169 Physician sample breakdown 169 US 169 Japan 169 France 170 Germany 170 Italy 171 Spain 171 UK 172 APPENDIX B 173 Physician survey questionnaire 173 Section 1: Epidemiology 173 Section 2: Prescribing patterns and disease severity 177 Section 3: Treatment patterns and disease severity 180 Section 4: Prescribing factors 187 Section 5: Treatment outcomes 189