Stakeholder Insight: Rheumatoid Arthritis - Biologics battle up the treatment algorithm

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