リウマチ性関節炎の治療動向

Abstract

Overview

Introduction

Rheumatoid arthritis is a debilitating and life-long disease that is estimated to affect approximately 5 million people in the seven major markets. The launch of anti-TNF products over six years ago and more recent novel target biologic therapies have added significantly to the treatment options, but have resulted in a crowded market for moderate to severe patients.

Scope

• Disease overview including epidemiology, physician estimated diagnosis rates and severity split, including mild to severe and early active disease
• Breakdown of treatment trends in the following markets: US, Japan, France, Germany, Italy, Spain and the UK
• PCPs and rheumatologists surveyed to capture the treatment of the ranging severities with traditional NSAIDs, COX-2s, traditional and biologic DMARDs
• Comparative brand assessment on the key attributes of Enbrel, Remicade, Humira, Orencia, Rituxan/MabThera, Kineret and methotrexate

Highlights

Inclusion of relevant early active RA patients in clinical studies will assist timely approval in this indication, increasing the patient base for any RA product. Definition of 'early' RA requires a balance between the physician ideal of less than 12 months, giving the best patient response, and capturing a substantial proportion of the market.

Physicians estimate nine months from disease onset to diagnosis. 25% of RA patients are estimated to be severe, and take an average of four months before the first DMARD is prescribed, being methotrexate in 60% of physicians. It can be 18-23 months before a severe patient is likely to use a biologic.

Anti-TNF therapy is expected to continue to dominate the first-line biologic use. Humira is perceived to be the most effective in terms of disease modification, indicating a very positive future status for this brand, but Remicade and Kineret could lose the brand battle if perception on certain attributes doesn't improve.

Reasons to Purchase

• Use estimated treatment class patient numbers to forecast product use across the seven major markets
• Exploit physician perceptions of key brands on clinical and market attributes, to differentiate products in the crowded rheumatoid arthritis market
• Understand differential treatment in niche populations such as severe and early active rheumatoid arthritis

Table of Contents

• About the CNS, Arthritis and Pain pharmaceutical analysis team
• CHAPTER 1 EXECUTIVE SUMMARY
  • Scope of the analysis
  • Datamonitor insight into the rheumatoid arthritis market
• CHAPTER 2 INTRODUCTION AND SCOPE
  • What is rheumatoid arthritis (RA)?
  • How is it treated?
  • Coverage of the Stakeholder Insight Survey
    • Country level "treatment trees"
    • Supporting data sets
• CHAPTER 3 COUNTRY TREATMENT TREES
  • US
  • Japan
  • France
  • Germany
  • Italy
  • Spain
  • UK
• CHAPTER 4 EPIDEMIOLOGY AND PATIENT SEGMENTATION
  • Definition of the disease
  • Epidemiology of rheumatoid arthritis
  • Key patient segmentations
    • Disease severity shows an even split among mild and moderate disease, with fewer severe patients
    • Early active RA should be defined as less than one-year duration for maximum patient benefit
  • Co-morbidities, complications and risk factors
    • Hypertension, elevated cholesterol and, to a lesser extent, heart attacks are common in RA patients
    • Osteoporosis is also common, but likely to be due to long-term steroid use
    • Depression is two to three times greater in RA patients than in the general population
    • Other co-morbidities include additional autoimmune diseases and stomach ulcers
• CHAPTER 5 DIAGNOSIS AND TREATMENT OPTIONS
  • Presentation and diagnosis lower than in previous Datamonitor surveys
  • Treatment types
    • Pharmacological and non-pharmacological therapy is often used in combination for moderate and severe patients
    • Use of combination drug therapy also increases with severity
    • NSAIDs, analgesics and traditional DMARDs are the most commonly prescribed drug classes
  • Treatment options
  • Treatment guidelines
  • Referral patterns
    • Direct consultation, or referral, for rheumatologists?
    • The next referral move
• CHAPTER 6 PRESCRIBING TRENDS
  • NSAID prescribing trends
    • The most commonly-used NSAID molecule is diclofenac
    • Use of NSAIDs and COX-2s since the withdrawal of Vioxx
    • High, and possibly inappropriate, co-prescription of a gastro-protective agent with NSAIDs
    • Use of NSAIDs before and in combination with DMARDs
  • Traditional DMARD prescribing trends
    • Methotrexate most commonly used as first-line therapy
    • Infection and inadequate response are the main reasons for switching
• CHAPTER 7 BRAND ASSESSMENT
  • Factors influencing physician decision making
    • Disease modification and side-effects are the most important factors to prescribing physicians
      • Disease modification
      • Side effects
      • Speed of action and pain relief
      • Formulary or reimbursement status
      • Dosing frequency and delivery method
      • Ability to combine
      • Ability to treat co-morbidities
      • Compliance
  • Biologic DMARD brand assessment
    • Biologic DMARD overview shows Enbrel leads in terms of total brand sales for all indications
    • Interpreting a brand map
      • As the gold standard traditional DMARD, methotrexate is used to benchmark the biologic treatments
      • The three available anti-TNFs are perceived to be similar
  • Brand comparison shows Humira and Enbrel lead the group
    • Enbrel (etanercept)
    • Remicade (infliximab)
    • Humira (adalimumab)
    • Kineret (anakinra)
    • Orencia (abatacept)
      • Rituxan/MabThera (rituximab)
• CHAPTER 8 IMPROVING TREATMENT OUTCOMES
  • Treatment outcomes
    • Outcome measure definitions
      • American College of Rheumatology 20, 50 and 70
      • Disease activity scale
      • Visual analogue scale
      • Erythrocyte sedimentation rate
      • C-reactive protein
      • Global Assessment
      • Health assessment questionnaire
      • Medical outcome short form 36 (SF-36) health survey
  • Physician patient conversation is the most commonly used outcome measure in the clinic
  • Expected outcome measures before and after anti-TNF treatment don't always correlate with published data
    • Expectation versus published results
  • Compliance rates improve with disease severity
    • Unmet needs
      • Efficacy and side-effects are key, but other challenges should also be addressed by the pharmaceutical industry
• APPENDIX A
  • Bibliography
    • Other sources and websites
• APPENDIX B
  • Physician research methodology
    • Physician sample breakdown
    • US
    • Japan
    • France
    • Germany
    • Italy
    • Spain
    • UK
  • Contributing experts
• APPENDIX C
  • The survey questionnaire
    • Section 1: Epidemiology
    • Section 2: Treatment classes and disease severity
    • Section 3: Prescribing factors
    • Section 4: Prescribing patterns
    • Section 5: Treatment outcomes
    • Disclaimer
  • List of Tables
    • Table 1: RA patient population, 2006
    • Table 2: Point prevalence of RA, by age and sex, per 100 patients in Norfolk UK study, 2002
    • Table 3: Estimated RA population based on population aged >60: CAGR for each country, 2005-2030
    • Table 4: RA disease severity as a percentage of total diagnosed RA population, by country
    • Table 5: Physician-estimated proportion of patients defined has having early active RA, by country
    • Table 6: Proportion of patients defined has having early active RA, by physician specialty
    • Table 7: Percentage of RA patients with each co-morbidity, by country
    • Table 8: Diagnosed RA patients, physician-estimated, by country
    • Table 9: Number of months from symptom onset to presentation to physician
    • Table 10: Percent of patients receiving pharmacological versus non-pharmacological treatment, by country
    • Table 11: Pharmacological versus non-pharmacological treatment, by physician specialty and percentage of diagnosed patients
    • Table 12: Percentage of patients on each number of drugs, by severity and by country
    • Table 13: Percentage of patients receiving each drug class, by severity
    • Table 14: Number of physicians using each set of guidelines, by physician specialty
    • Table 15: Percentage of mild, moderate and severe RA patients referred on to another physician, by specialty
    • Table 16: Percentage of physicians referring to each specialty, by country
    • Table 17: Percentage of patients receiving each NSAID molecule, by severity
    • Table 18: Action taken on traditional NSAID prescribing, percentage of physicians, by country,
    • Table 19: Action taken on COX-2 prescribing, percentage of physicians, by country
    • Table 20: Average length of time RA patients are given only an analgesic/ anti-inflammatory before being prescribed a DMARD, in months, by severity and country
    • Table 21: Percentage of RA patients taking analgesic or anti-inflammatory treatment in addition to a DMARD, by severity and country
    • Table 22: Percentage of patients on traditional DMARDs receiving key molecules, by country and severity
    • Table 23: Number and percentage of physicians able to rate each brand
    • Table 24: Comparative erosion and joint space narrowing (JSN) scores after 12 months, found in prescribing information, by brand
    • Table 25: Efficacy comparison among key brands
    • Table 26: Key biologic brand characteristics
    • Table 27: Methotrexate's attribute scores, by country
    • Table 28: Enbrel's attribute scores, by country
    • Table 29: Remicade's attribute scores, by country
    • Table 30: Humira attribute scores, by country
    • Table 31: Kineret attribute scores, by country
    • Table 32: Orencia's attribute scores, by country
    • Table 33: Rituxan/MabThera's attribute scores, by country
    • Table 34: Healthy ESR values
    • Table 35: Commonly used outcome measures, by country
    • Table 36: Average expected outcome measures before and after anti-TNF therapy
    • Table 37: Published anti-TNF impacts on key outcome measures
    • Table 38: Average VAS before and after anti-TNF therapy
    • Table 39: Rheumatologist estimates of 28 tender and swollen joint counts before and after anti-TNF therapy
    • Table 40: Compliance estimates by disease severity
    • Table 41: Importance of challenges facing the RA market, by country
    • Table 42: US physician sample breakdown, 2006
    • Table 43: Japan physician sample breakdown, 2006
    • Table 44: France physician sample breakdown, 2006
    • Table 45: Germany physician sample breakdown, 2006
    • Table 46: Italy physician sample breakdown, 2006
    • Table 47: Spain physician sample breakdown, 2006
    • Table 48: UK physician sample breakdown, 2006
  • List of Figures
    • Figure 1: Overview of the coverage of Stakeholder Insight: Rheumatoid Arthritis survey, 2006
    • Figure 2: US RA patient population, split by physician-estimated diagnoses, disease severity, drug-treated population and drug-class usage
    • Figure 3: Key NSAID, traditional DMARD and biologic DMARD molecules used in the US, by disease severity
    • Figure 4: US treatment algorithm from onset of symptoms to percentage reaching desired outcome, for NSAIDs and first- to fifth-line DMARDs, by disease severity
    • Figure 5: Japan RA patient population, split by estimated diagnoses, disease severity, drug-treated population and drug-class usage
    • Figure 6: Key NSAID, traditional DMARD and biologic DMARD molecules used in Japan, by disease severity
    • Figure 7: Japanese treatment algorithm from onset of symptoms to percentage reaching desired outcome, for NSAIDs and first- to fifth-line DMARDs, by disease severity
    • Figure 8: France RA patient population, split by physician-estimated diagnoses, disease severity, drug-treated population and drug-class usage
    • Figure 9: Key NSAID, traditional DMARD and biologic DMARD molecules used in France, by disease severity
    • Figure 10: France treatment algorithm from onset of symptoms to percentage reaching desired outcome, for NSAIDs and first- to fifth-line DMARDs, by disease severity
    • Figure 11: Germany RA patient population, split by physician-estimated diagnoses, disease severity, drug-treated population and drug-class usage
    • Figure 12: Key NSAID, traditional DMARD and biologic DMARD molecules used in Germany, by disease severity
    • Figure 13: Germany treatment algorithm from onset of symptoms to percentage reaching desired outcome, for NSAIDs and first- to fifth-line DMARDs, by disease severity
    • Figure 14: Italy RA patient population, split by physician-estimated diagnoses, disease severity, drug-treated population and drug-class usage
    • Figure 15: Key NSAID, traditional DMARD and biologic DMARD molecules used in Italy, by disease severity
    • Figure 16: Italy treatment algorithm from onset of symptoms to percentage reaching desired outcome, for NSAIDs and first- to fifth-line DMARDs, by disease severity
    • Figure 17: Spain RA patient population, split by physician-estimated diagnoses, disease severity, drug-treated population and drug-class usage
    • Figure 18: Key NSAID, traditional DMARD and biologic DMARD molecules used in Spain, by disease severity
    • Figure 19: Spain treatment algorithm from onset of symptoms to percentage reaching desired outcome, for NSAIDs and first- to fifth-line DMARDs, by disease severity
    • Figure 20: UK RA patient population, split by physician-estimated diagnoses, disease severity, drug-treated population and drug-class usage
    • Figure 21: Key NSAID, traditional DMARD and biologic DMARD molecules used in UK, by disease severity
    • Figure 22: UK treatment algorithm from onset of symptoms to percentage reaching desired outcome, for NSAIDs and first- to fifth-line DMARDs, by disease severity
    • Figure 23: Percentage of physicians with RA patients who have at least one co-morbidity
    • Figure 24: Prevalence of hypertension in US RA patients, 2004
    • Figure 25: Treatment algorithm for RA
    • Figure 26: Percentage of physicians using each set of guidelines, by country
    • Figure 27: Number of physicians using different guidelines, by specialty
    • Figure 28: Percentage of patients consulting a rheumatologist directly or via referral, by country
    • Figure 29: Percentage of mild, moderate and severe RA patients referred on to another physician, by specialty
    • Figure 30: Percentage of physicians that refer to each specialist type, split by PCPs and rheumatologists
    • Figure 31: US NSAID/COX-2 quarterly prescriptions (Rx), 2003-2005
    • Figure 32: Percentage of drug-treated RA patients receiving celecoxib and etoricoxib, by country
    • Figure 33: Trend in prescribing of NSAIDs and COX-2s after the withdrawal of Vioxx
    • Figure 34: Results of Jack Cush's US physician survey, November 2005
    • Figure 35: Decision tree for physicians treating arthritis patients developing GI complications with NSAIDs
    • Figure 36: Percentage of NSAID-treated patients also receiving a gastro-protective agent, by country and by physician specialty
    • Figure 37: Co-prescription of a PPI with an NSAID, comparing RA to all indications, % RX-Days, 2005
    • Figure 38: Percentage of RA patients using NSAIDs (including COX-2s), by physician specialty and by disease severity
    • Figure 39: Most commonly used traditional DMARD molecules, by disease severity
    • Figure 40: Number of months a patient will be continued on DMARD therapy before moving to the next line of therapy, by country and by physician specialty
    • Figure 41: Percentage of physicians using DMARD molecules at each line of therapy
    • Figure 42: Percentage of patients on biologics switching or terminating therapy, and key reasons
    • Figure 43: Average influence on prescribing decision: weightings assigned by surveyed physicians to key attributes for biologic and traditional DMARDs
    • Figure 44: Biologic and traditional DMARD attribute weightings assigned by physicians, by country
    • Figure 45: Comparative erosion and JSN scores, by brand
    • Figure 46: Physicians' scores of disease-modification efficacy, by brand
    • Figure 47: Importance of side effects to prescribing of biologic and traditional DMARDs, by country and by physician specialty
    • Figure 48: Physicians' scores of side effects, by brand
    • Figure 49: Comparative ACR 20, 50 and 70 scores for biologic therapies based on their prescribing information
    • Figure 50: Physicians' scores for therapeutic efficacy attributes, by brand
    • Figure 51: Importance of reimbursement/formulary status to prescribing of biologic and traditional DMARDs, by country and by physician specialty
    • Figure 52: Importance of dosing frequency and delivery method to prescribing of biologic and traditional DMARDs, by country and by physician specialty
    • Figure 53: Total biologics brand sales, seven major markets, $m
    • Figure 54: Comparison of total scores for all brands rated, by country and specialist
    • Figure 55: Total score for each brand across the seven major markets
    • Figure 56: Overview brand map of attributes versus brand perception
    • Figure 57: Physician perception of the anti-TNF inhibitors
    • Figure 58: Enbrel map, country preference to prescribing attributes
    • Figure 59: Remicade map, country preference to prescribing attributes
    • Figure 60: Humira attribute scores
    • Figure 61: Kineret attribute scores
    • Figure 62: Orencia attribute scores
    • Figure 63: Rituxan/MabThera attribute scores
    • Figure 64: Patient assessment form, American College of Rheumatology
    • Figure 65: Physician's global assessment
    • Figure 66: Commonly used outcome measures, by specialist
    • Figure 67: Comparison between survey results for expected improvement in disease activity measures after anti-TNF and prescribing information data
    • Figure 68: Average VAS before and after anti-TNF therapy
    • Figure 69: Swollen and tender joint count assessment
    • Figure 70: Compliance estimates by disease severity
    • Figure 71: Reasons why patients do not fill prescriptions or comply with drug regimes, 2002
    • Figure 72: Importance of challenges facing the RA market
    • Figure 73: IFPMA clinical trials portal