炎症性大腸炎

Abstract

Overview

Introduction

Inflammatory bowel disease (IBD) is a chronic inflammatory condition that affects the gastrointestinal tract causing a number of distressing symptoms such as bleeding, diarrhea and abdominal pain. IBD includes key subsets Crohn' s disease and ulcerative colitis, both of which can significantly impact on the quality of life of an individual.

Scope

• Analysis of the inflammatory bowel disease market based on a survey of 180 gastroenterologists supported by key opinion leader interviews
• Overview of epidemiology and patient segmentation in IBD
• Influences on gastroenterologists' prescribing behavior and their perception of current brands such as Remicade, Humira, Pentasa, Asacol and Lialda
• Assessment of outcomes of treatment with Remicade focusing on treatment failure and reasons for failure

Highlights

Clinical guidelines recommend a step-up treatment approach. However, Datamonitor' s survey suggests that currently 20% of patients with severe IBD currently receive an early aggressive treatment approach. There is an ongoing debate among Gastroenterologists and Datamonitor believe this approach will become more commonplace in the future.

Remicade remains the first choice biologic therapy in 80% of biologic-naïve patients. However, Humira has distinct advantages over Remicade that will lead to strong. Humira is positioned as a treatment for Remicade-failure patients, but Datamonitor' s survey suggests currently only 30% of these patients go on to receive Humira.

Shire' s Lialda (mesalazine), recently launched as a once-daily drug, is perceived by gastroenterologists to perform well on patient compliance. In a drug class where there is little differentiation between brands over efficacy and safety, Lialda will provide a clinical advantage thanks to its improved dosing regimen.

Reasons to Purchase

• Target prescribers more effectively, through an understanding of prescribing behavior and influencing factors
• Validate new product forecasting based on diagnosis and treatment rates, and the likely rate of uptake for new products
• Benchmark brand awareness and perceptions surrounding product positioning in order to formulate competitive lifecycle management strategies

Table of Contents

• ABOUT DATAMONITOR HEALTHCARE
  • About the Immunology and Inflammation pharmaceutical analysis team
• CHAPTER 1 EXECUTIVE SUMMARY
  • Scope of the analysis
  • Datamonitor insight into the inflammatory bowel disease market
  • Contributing experts
  • Previous and related reports
• CHAPTER 2 INTRODUCTION AND SCOPE
  • Coverage of the Stakeholder Insight Survey
    • Epidemiology and patient segmentation
    • Diagnosis
    • Treatment options and guidelines
    • Treatment trends
    • Key prescribing influences
    • Brand assessment
• CHAPTER 3 COUNTRY TREATMENT TREES
  • Introduction to treatment trees
    • US
    • Japan
    • France
    • Germany
    • Italy
    • Spain
    • UK
• CHAPTER 4 EPIDEMIOLOGY AND PATIENT SEGMENTATION
  • Disease definition
    • Classification of inflammatory bowel disease
      • Crohn' s disease
      • Ulcerative colitis
      • Montreal classification of Crohn' s disease and ulcerative colitis
    • Etiology
      • Genes associated with inflammatory bowel disease influence phenotype
      • Smoking
      • Appendectomy
      • Oral contraceptives
      • Infection with a pathogenic organism
      • Abnormal immune response to gut flora
    • Pathogenesis
      • Crohn' s disease and ulcerative colitis are mediated by Th1 and Th2 lymphocytes, respectively
  • Disease incidence and prevalence
    • Crohn' s disease
    • Ulcerative colitis
    • US
    • Europe
      • France
      • Germany
      • Italy
      • Spain
      • UK
    • Japan
    • Patient segmentation according to disease severity
      • Severity is measured using different disease activity scales
      • Majority of Crohn' s disease and ulcerative colitis patients suffer mild to moderate disease
• CHAPTER 5 DIAGNOSIS OF INFLAMMATORY BOWEL DISEASE
  • Diagnosis
    • Diagnosis of inflammatory bowel disease combines many avenues of investigation
      • Initial investigation begins with laboratory tests
      • Endoscopy is the most direct way of diagnosing inflammatory bowel disease
      • Radiology is a crucial adjunct to endoscopy
      • Serological markers are not yet used for clinical diagnosis
    • A high diagnosis rate is observed in inflammatory bowel disease
      • Just over 70% of Crohn' s disease patients are diagnosed
      • Physicians report a higher diagnosis rate for ulcerative colitis than Crohn' s disease
    • Complications arising in Crohn' s disease and ulcerative colitis
      • Abscesses, strictures and fistulae are the most commonly physician-reported complications in Crohn' s disease patients
      • Over 25% of Crohn' s disease patients suffer from nutritional deficiencies
      • Bleeding is reported by almost all gastroenterologists in patients with ulcerative colitis
      • Almost half of ulcerative colitis patients experience bleeding complications
    • Association of IBD with immune disorders and co-morbidities
      • Anemia and anxiety and depression are the most commonly associated co-morbidities in inflammatory bowel disease
      • Patients with inflammatory bowel disease also suffer from irritable bowel disease
      • Immune-mediated diseases occur at greater frequency among patients with inflammatory bowel disease
• CHAPTER 6 TREATMENT OPTIONS AND GUIDELINES
  • Treatment options
    • Non-pharmacological treatment of inflammatory bowel disease
      • Diet
      • Probiotics
    • Pharmacological treatment
      • Antibiotics
      • Anti-diarrheals and anti-spasmodics
      • Topical and oral aminosalicylates
      • Corticosteroids
      • Traditional immunosuppressants
      • Targeted biologics
    • Pharmacological versus non-pharmacological
      • Majority of patients with inflammatory bowel disease are treated pharmacologically
      • There are some patients who do not receive any therapy for inflammatory bowel disease
  • Treatment guidelines
    • Several treatment guidelines exist for the treatment of inflammatory bowel disease
      • Guidelines published by the British Society of Gastroenterology
      • NICE guidelines on the use of infliximab for Crohn' s disease
      • NICE is appraising the use of infliximab for ulcerative colitis
      • American College of Gastroenterology guidelines for Crohn' s disease
      • American College of Gastroenterology guidelines for ulcerative colitis
      • The European Crohn' s and Colitis Organisation has published consensus guidelines for Crohn' s disease
• CHAPTER 7 TREATMENT TRENDS
  • Changes in therapy
    • Disease severity influences treatment
      • Despite lack of evidence to support efficacy, Crohn' s disease and ulcerative colitis patients receive antibiotics at all levels of severity
      • Anti-spasmodics and anti-diarrheals are used as accompanying therapies for all severities of Crohn' s disease and ulcerative colitis
      • Up to 60% of Crohn' s disease and ulcerative colitis patients receive oral aminosalicylates
      • Topical aminosalicylates are used more for ulcerative colitis than Crohn' s disease
      • Use of corticosteroids increases with disease severity
      • Gradual increase in use of immunosuppressants according to Crohn' s disease severity
      • Immunosuppressants are largely reserved for moderate and severe ulcerative colitis patients
      • Use of biologics in Crohn' s disease occurs in moderate-to-severe disease, but to a limited extent in mild patients
      • Use of biologic increases significantly with severity of ulcerative colitis
    • Monotherapy versus combination therapy
      • Increasing disease severity promotes use of combination therapy
    • First-line therapy
      • Oral 5-ASAs are used first-line for Crohn' s disease
      • Corticosteroids are being prescribed at first-line for Crohn' s disease
      • A combination of oral and topical 5-ASAs is the preferred first-line treatment regimen for ulcerative colitis
      • Almost 45% of Crohn' s disease patients move to a second-line therapy
      • About a third of ulcerative colitis patients progress to treatment with second-line therapy
    • Second-line therapy
      • Immunosuppressants are the most commonly prescribed drug class by gastroenterologists at second-line for Crohn' s disease
      • Biologics are prescribed at second-line for Crohn' s disease
      • Corticosteroids are prescribed at second-line for ulcerative colitis
      • Immunosuppressants are also prescribed at second-line for ulcerative colitis
      • Almost a quarter of Crohn' s disease patients progress from second-line to third-line treatment
      • A fifth of ulcerative colitis patients progress from second-line to third-line treatment
    • Third-line therapy
      • Biologics alone, or in combination with immunosuppressants, are the most commonly prescribed therapies for Crohn' s disease at third-line
      • Like Crohn' s disease, biologics are prescribed most frequently by gastroenterologists for ulcerative colitis
  • Surgery
    • Surgery is more effective for ulcerative colitis than Crohn' s disease
    • Just under a third of Crohn' s disease patients will eventually require surgery
    • Almost half as many patients with ulcerative colitis will eventually require surgery than those with Crohn' s disease
    • Ulcerative colitis patients receive pharmacological therapy for longer than Crohn' s disease patients before requiring surgery
  • "Step-up" versus a "top-down" approach to the treatment of inflammatory bowel disease
    • Current algorithms promote use of a "step-up" approach, but a "top-down" approach is now being suggested
    • Is there scope for a "top-down" approach?
      • Clinical trial data provide evidence showing a "top-down" approach is more effective than "step-up"
      • A "top-down" approach may change the natural history of Crohn' s disease
      • There are a number of advantages and risks associated with a "top-down" treatment approach
      • The SONIC study will assess early use of azathioprine, infliximab or both in combination
    • Only 20% of severe Crohn' s disease patients receive a "top-down" treatment approach
    • The potential for side effects ranks as the leading reason for not using a "top-down" approach in Crohn' s disease
    • Similar percentage of ulcerative colitis and Crohn' s disease patients receive a "top-down" treatment approach
    • The potential for side effects is also the leading reason for not using a "top-down" approach in ulcerative colitis
    • Gastroenterologists also reported that a lack of evidence and experience prevents use of a "top-down" approach
• CHAPTER 8 PRESCRIBING INFLUENCES
  • Factors influencing physician decision making
    • Symptomatic improvement and healing of the mucosa are the most important factors influencing physician prescribing
    • Efficacy
      • Symptomatic improvement
      • Efficacy in promoting mucosal healing
      • Speed of onset of remission
    • Safety
      • Side-effect profile
    • Dosing
      • Convenient dosing and convenient administration frequency
    • Cost
      • Availability (formulary/reimbursement status)
    • Physician factors
      • Familiarity with product
    • Patient factors
      • Patient compliance
    • Other
      • Prevention of colon cancer
• CHAPTER 9 BRAND ASSESSMENT
  • Brand map
    • How to interpret a brand map
  • 5-ASAs: Lialda may offer advantages in a class where there is little differentiation
    • Pentasa (mesalazine)
      • Pentasa is an oral, controlled-release formulation that delivers mesalazine from the duodenum to the rectum
      • New dose of Pentasa reduces the number of pills taken per day
      • Gastroenterologists rated Pentasa well on familiarity and availability
    • Lialda/Mezavant (mesalazine)
      • Lialda is an oral sustained-release, multimatrix formulation of mesalamine
      • Lialda is marketed as a once-daily treatment for ulcerative colitis
      • Lialda has been compared with Asacol in a Phase III clinical trial
      • Gastroenterologists scored Lialda well on side-effect profile
      • Lialda is perceived by gastroenterologists to perform well on patient compliance, convenient dose and convenient administration frequency
    • Asacol (mesalazine)
      • Asacol is a delayed-release formulation of mesalazine, which is marketed by Proctor & Gamble
      • Asacol well perceived on familiarity with product and availability
    • Salofalk (mesalazine)
      • Salofalk is a Eudragit-L-coated pellet formulation of mesalazine
      • Salofalk and Pentasa are equally effective in achieving remission in mild to moderate ulcerative colitis patients
      • Salofalk did not perform well on patient compliance and convenient administration frequency
    • Claversal (mesalazine)
      • Like Salofalk, Claversal is a micropellet formulation of mesalazine
    • Fivasa (mesalazine)
      • In France, Asacol is marketed as Fivasa by Norgine Pharma
    • Salazopyrin (sulfasalazine)
      • Gastroenterologists did not rate Salazopyrin well on side-effect profile
  • Biologics: brand comparison shows that Remicade remains the leader, but Humira is perceived well by physicians
    • Remicade (infliximab)
      • Gastroenterologists rate Remicade well on familiarity with product and symptomatic improvement
      • Mucosal healing is associated most with Remicade than the other biologics
      • Remicade is not associated with a convenient dose and convenient administration frequency
      • More than three-quarters of severe patients with inflammatory bowel disease receive Remicade as their first biologic therapy
      • 40% of patients who receive Remicade as their first biologic will terminate therapy
      • Most patients terminate Remicade therapy within the first year
      • An inadequate response is the most common reason for terminating Remicade therapy within the first year
      • Inadequate response remains the most common reason for terminating Remicade therapy after 1 year
      • Over a third of patients who fail Remicade therapy will move on to treatment with Humira
      • Surgery is the next step for many patients who fail Remicade therapy
      • Almost a quarter of Remicade-refractory patients progress to therapy with corticosteroids
      • Despite no evidence of efficacy in Crohn' s disease, a small percentage of Remicade-refractory patients go on to receive Enbrel (etanercept)
    • Humira (adalimumab)
      • Humira is a self-administered, fully human anti-TNF monoclonal antibody
      • Clinical trials for Humira demonstrate efficacy in biologic-naïve patients and infliximab-refractory patients with Crohn' s disease
      • Gastroenterologists scored Humira better than Remicade on a number of attributes
    • Cimzia (certolizumab pegol)
      • Cimzia is a pegylated, humanized anti-TNF therapy
      • PRECISE 1 and PRECISE 2 trials demonstrated the safety and efficacy of Cimzia, but the therapy was rejected by the FDA
      • Cimzia was rejected for Crohn' s disease in the EU in November 2007
      • Cimzia was perceived by gastroenterologists to perform well on convenient dose and administration frequency
    • Tysabri (natalizumab)
      • Tysabri prevents leukocytes migrating into the gut in Crohn' s disease
      • The EMEA' s CHMP returned a final negative opinion for Tysabri in Crohn' s disease in November 2007
      • The ENACT and ENCORE trials demonstrated the efficacy of Tysabri in Crohn' s disease
      • Tysabri was not rated well on symptomatic improvement or side-effect profile
• BIBLIOGRAPHY
  • Journal papers
  • Websites
  • Other
• APPENDIX A
  • Physician research methodology
    • Physician sample breakdown
    • US
    • Japan
    • France
    • Germany
    • Italy
    • Spain
    • UK
  • Contributing experts
• APPENDIX B
  • The survey questionnaire
    • 1. Patient Segmentation
    • 2. Prescribing factors
    • 3. Treatment classes and severity
    • 4. Treatment of severe disease
• APPENDIX C
  • About Datamonitor
    • About Datamonitor Healthcare
    • About the Immunology and Inflammation analysis team
    • Disclaimer
  • List of Tables
    • Table 1: Montreal sub-classification for Crohn' s disease, 2005
    • Table 2: Montreal classification for ulcerative colitis covering extent and anatomy, 2005
    • Table 3: Epidemiological studies into incidence and prevalence of Crohn' s disease and ulcerative colitis, 1978─2007
    • Table 4: Prevalence and incidence of Crohn' s disease in the seven major markets by country, 2007
    • Table 5: Prevalence and incidence of ulcerative colitis in the seven major markets by country, 2007
    • Table 6: Age- and sex-specific and adjusted prevalence of ulcerative colitis in Olmsted County, Minnesota, January 2001
    • Table 7: Age- and sex-specific and adjusted prevalence of Crohn' s disease in Olmsted County, Minnesota, January 2001
    • Table 8: Incidence and prevalence of Crohn' s disease and ulcerative colitis in the UK, 1995
    • Table 9: Annual prevalence and incidence of Crohn' s disease and ulcerative colitis in Japan, 1991
    • Table 10: Number of respondents reporting Crohn' s disease patients with each complication, by country, 2007
    • Table 11: Number of respondents reporting ulcerative colitis patients with each complication, by country, 2007
    • Table 12: Number and percentage of gastroenterologists prescribing each therapy at first-line for Crohn' s disease, 2007
    • Table 13: Number and percentage of gastroenterologists prescribing each therapy at first-line for ulcerative colitis, 2007
    • Table 14: Number and percentage of gastroenterologists prescribing each therapy at second-line for Crohn' s disease, 2007
    • Table 15: Number and percentage of gastroenterologists prescribing each therapy at second-line for ulcerative colitis, 2007
    • Table 16: Number and percentage of gastroenterologists prescribing each therapy at third-line for Crohn' s disease
    • Table 17: Number and percentage of gastroenterologists prescribing each therapy at third-line for ulcerative colitis
    • Table 18: Mean ranking for each reason for not using a top-down approach in severe Crohn' s disease, 2007
    • Table 19: Mean ranking for each reason for not using a top-down approach in severe ulcerative colitis, 2007
    • Table 20: Number and percentage of physicians able to rate each brand of 5-ASA
    • Table 21: Number and percentage of physicians able to rate each brand of biologic
    • Table 22: Comparison of key studies for Remicade, Humira, Cimzia and Tysabri
    • Table 23: Side effects associated with sulfasalazine and 5-ASAs
    • Table 24: Dosing schedule for the 5-ASA brands
    • Table 25: Attributes scores for each of the 5-ASA brands
    • Table 26: Attributes scores for each of the biologic brands
    • Table 27: Remicade' s attribute scores by country
    • Table 28: Percentage of patients who terminate Remicade therapy in each time period, by country
    • Table 29: Percentage of inflammatory bowel disease patients terminating Remicade therapy within the first year because of each reason, by country
    • Table 30: Percentage of inflammatory bowel disease patients terminating Remicade therapy after the first year because of each reason, by country
    • Table 31: Percentage of inflammatory bowel disease patients who fail Remicade therapy that are switched to Humira (adalimumab), by country, 2007
    • Table 32: Percentage of Remicade-refractory patients who move on to therapy with Enbrel (etanercept), by country
    • Table 33: Cimzia' s attribute scores, by country
    • Table 34: US physician sample breakdown, 2007
    • Table 35: Japan physician sample breakdown, 2007
    • Table 36: France physician sample breakdown, 2007
    • Table 37: Germany physician sample breakdown, 2007
    • Table 38: Italy physician sample breakdown, 2007
    • Table 39: Spain physician sample breakdown, 2007
    • Table 40: UK physician sample breakdown, 2007
  • List of Figures
    • Figure 1: Crohn' s disease treatment tree split by disease severity in the US, 2007
    • Figure 2: Ulcerative colitis treatment tree split by disease severity in the US, 2007
    • Figure 3: Physician-preferred first-, second- and third-line treatment regimen for Crohn' s disease in the US, 2007
    • Figure 4: Physician-preferred first-, second- and third-line treatment regimen for ulcerative colitis in the US, 2007
    • Figure 5: Crohn' s disease treatment tree split by disease severity in Japan, 2007
    • Figure 6: Ulcerative colitis treatment tree split by disease severity in Japan, 2007
    • Figure 7: Physician-preferred first-, second- and third-line treatment regimen for Crohn' s disease in Japan, 2007
    • Figure 8: Physician-preferred first-, second- and third-line treatment regimen for ulcerative colitis in Japan, 2007
    • Figure 9: Crohn' s disease treatment tree split by disease severity in France, 2007
    • Figure 10: Ulcerative colitis treatment tree split by disease severity in France, 2007
    • Figure 11: Physician-preferred first-, second- and third-line treatment regimen for Crohn' s disease in France, 2007
    • Figure 12: Physician-preferred first-, second- and third-line treatment regimen for ulcerative colitis in France, 2007
    • Figure 13: Crohn' s disease treatment tree split by disease severity in Germany, 2007
    • Figure 14: Ulcerative colitis treatment tree split by disease severity in Germany, 2007
    • Figure 15: Physician-preferred first-, second- and third-line treatment regimen for Crohn' s disease in Germany, 2007
    • Figure 16: Physician-preferred first-, second- and third-line treatment regimen for ulcerative colitis in Germany, 2007
    • Figure 17: Crohn' s disease treatment tree split by disease severity in Italy, 2007
    • Figure 18: Ulcerative colitis treatment tree split by disease severity in Italy, 2007
    • Figure 19: Physician-preferred first-, second- and third-line treatment regimen for Crohn' s disease in Italy, 2007
    • Figure 20: Physician-preferred first-, second- and third-line treatment regimen for ulcerative colitis in Italy, 2007
    • Figure 21: Crohn' s disease treatment tree split by disease severity in Spain, 2007
    • Figure 22: Ulcerative colitis treatment tree split by disease severity in Spain, 2007
    • Figure 23: Physician-preferred first-, second- and third-line treatment regimen for Crohn' s disease in Spain, 2007
    • Figure 24: Physician-preferred first-, second- and third-line treatment regimen for ulcerative colitis in Spain, 2007
    • Figure 25: Crohn' s disease treatment tree split by disease severity in the UK, 2007
    • Figure 26: Ulcerative colitis treatment tree split by disease severity in the UK, 2007
    • Figure 27: Physician-preferred first-, second- and third-line treatment regimen for Crohn' s disease in the UK, 2007
    • Figure 28: Physician-preferred first-, second- and third-line treatment regimen for ulcerative colitis in the UK, 2007
    • Figure 29: Age- and sex-adjusted incidence of Crohn' s disease and ulcerative colitis in Olmsted County, Minnesota, 1940-2000
    • Figure 30: Estimated annual prevalence and incidence rates of Crohn' s disease in Japan, 1986-1998
    • Figure 31: Diagnosed Crohn' s disease patients by severity in the seven major markets, 2007
    • Figure 32: Diagnosed ulcerative colitis patients by severity in the seven major markets, 2007
    • Figure 33: Diagnosis of inflammatory bowel disease
    • Figure 34: Crohn' s disease diagnosis rates, by country, 2007
    • Figure 35: Ulcerative colitis diagnosis rates, by country, 2007
    • Figure 36: Percentage of Crohn' s disease patients suffering from each complication, 2007
    • Figure 37: Percentage of ulcerative colitis patients suffering from each complication, 2007
    • Figure 38: Percentage of inflammatory bowel disease patients with various co-morbidities, 2007
    • Figure 39: Mean percentage of Crohn' s disease patients receiving each type of therapy by disease severity, 2007
    • Figure 40: Mean percentage of ulcerative colitis patients receiving each type of therapy by disease severity, 2007
    • Figure 41: Percentage of patients with Crohn' s disease not receiving treatment, split by disease severity, by country, 2007
    • Figure 42: Percentage of patients with ulcerative colitis not receiving treatment, split by disease severity, by country, 2007
    • Figure 43: American College of Gastroenterology: Management of Crohn' s disease in adults
    • Figure 44: Algorithm for the medical management of Crohn' s disease, 2003
    • Figure 45: American College of Gastroenterology: Ulcerative colitis practice guidelines in adults
    • Figure 46: Percentage of Crohn' s disease patients receiving antibiotics by disease severity in the seven major markets, 2007
    • Figure 47: Percentage of ulcerative colitis patients receiving antibiotics by disease severity in the seven major markets, 2007
    • Figure 48: Percentage of Crohn' s disease patients receiving anti-spasmodics by disease severity in the seven major markets, 2007
    • Figure 49: Percentage of ulcerative colitis patients receiving anti-spasmodics by disease severity in the seven major markets, 2007
    • Figure 50: Percentage of Crohn' s disease patients receiving anti-diarrheals by disease severity in the seven major markets, 2007
    • Figure 51: Percentage of ulcerative colitis patients receiving anti-diarrheals by disease severity in the seven major markets, 2007
    • Figure 52: Percentage of Crohn' s disease patients receiving oral 5-ASAs by disease severity in the seven major markets, 2007
    • Figure 53: Percentage of ulcerative colitis patients receiving oral 5-ASAs by disease severity in the seven major markets, 2007
    • Figure 54: Percentage of Crohn' s disease patients receiving topical 5-ASAs by disease severity in the seven major markets, 2007
    • Figure 55: Percentage of ulcerative colitis patients receiving topical 5-ASAs by disease severity in the seven major markets, 2007
    • Figure 56: Percentage of Crohn' s disease patients receiving corticosteroids by disease severity in the seven major markets, 2007
    • Figure 57: Percentage of ulcerative colitis patients receiving corticosteroids by disease severity in the seven major markets, 2007
    • Figure 58: Percentage of Crohn' s disease patients receiving traditional immunosuppressants by disease severity in the seven major markets, 2007
    • Figure 59: Percentage of ulcerative colitis patients receiving traditional immunosuppressants by disease severity in the seven major markets, 2007
    • Figure 60: Percentage of Crohn' s disease patients receiving biological therapy by disease severity in the seven major markets, 2007
    • Figure 61: Percentage of ulcerative colitis patients receiving biological therapy by disease severity in the seven major markets, 2007
    • Figure 62: Percentage of mild Crohn' s disease patients receiving monotherapy or combination therapy in the seven major markets, 2007
    • Figure 63: Percentage of moderate Crohn' s disease patients receiving monotherapy or combination therapy in the seven major markets, 2007
    • Figure 64: Percentage of severe Crohn' s disease patients receiving monotherapy or combination therapy in the seven major markets, 2007
    • Figure 65: Percentage of mild ulcerative colitis patients receiving monotherapy or combination therapy in the seven major markets, 2007
    • Figure 66: Percentage of moderate ulcerative colitis patients receiving monotherapy or combination therapy in the seven major markets, 2007
    • Figure 67: Percentage of severe ulcerative colitis patients receiving monotherapy or combination therapy in the seven major markets, 2007
    • Figure 68: Percentage of Crohn' s disease patients progressing from first-line to second-line treatment regimen, by country, 2007
    • Figure 69: Percentage of ulcerative colitis patients progressing from first-line to second-line treatment regimen, by country
    • Figure 70: Percentage of Crohn' s disease patients progressing from second-line to third-line treatment regimen, by country
    • Figure 71: Percentage of ulcerative colitis patients progressing from second-line to third-line treatment regimen, by country
    • Figure 72: Percentage of Crohn' s disease patients that will eventually require surgery, by country
    • Figure 73: Percentage of ulcerative colitis patients that will eventually require surgery, by country
    • Figure 74: Number of years a Crohn' s disease or ulcerative colitis patient will receive pharmacological therapy before requiring surgery, by country
    • Figure 75: Step-up versus a top-down treatment approach
    • Figure 76: Results of the first "top-down" versus "step-up" randomized controlled trial presented at the DDW 2006
    • Figure 77: Potential advantages and risks of a "top-down" treatment approach
    • Figure 78: Percentage of Crohn' s disease and ulcerative colitis patients receiving a biologic in combination with an Immunosuppressant, by country, 2007
    • Figure 79: Percentage of severe Crohn' s disease patients who receive a step-up versus a top-down treatment approach, by country, 2007
    • Figure 80: Percentage of severe ulcerative colitis patients who receive a step-up versus a top-down treatment approach, by country, 2007
    • Figure 81: Reasons, and frequency of each reason, for not using a "top-down" treatment approach in Crohn' s disease, 2007
    • Figure 82: Reasons, and frequency of each reason, for not using a "top-down" treatment approach in ulcerative colitis, 2007
    • Figure 83: Average influence on prescribing decision: weightings assigned by gastroenterologists to key attributes for 5-ASAs and biologics, 2007
    • Figure 84: Weightings for attributes in 5-ASAs and targeted biologics assigned by physicians, by country, 2007
    • Figure 85: Importance of symptomatic improvement to prescribing of 5-ASAs and biologics, by country, 2007
    • Figure 86: Importance of efficacy in promoting mucosal healing to prescribing of 5-ASAs and biologics, by country, 2007
    • Figure 87: Physicians' scores for mucosal healing and symptomatic improvement for biologic brands, 2007
    • Figure 88: Importance of speed of onset of remission to prescribing of 5-ASAs and biologics by country, 2007
    • Figure 89: Dosing schedule for biologics in Crohn' s disease
    • Figure 90: Importance of availability to prescribing of 5-ASAs and biologics by country, 2007
    • Figure 91: Importance of familiarity with product to prescribing of 5-ASAs and biologics by country, 2007
    • Figure 92: Overview brand map of attributes versus brand perception for 5-ASAs and biologics
    • Figure 93: Brand map of the marketed 5-ASAs
    • Figure 94: Brand map of the marketed and pipeline targeted biologics
    • Figure 95: Pentasa' s attribute scores
    • Figure 96: Dosing of Lialda for ulcerative colitis
    • Figure 97: Attribute scores for Lialda/Mezavant
    • Figure 98: Attribute scores for Asacol
    • Figure 99: Physician perception of the targeted biologics
    • Figure 100: Attribute scores for Remicade
    • Figure 101: Gastroenterologists' scores for mucosal healing for the biologics
    • Figure 102: Mean percentage of inflammatory bowel disease patients receiving each drug as their first biologic, 2007
    • Figure 103: Percentage of patients with inflammatory bowel disease receiving Remicade as their first biologic who will terminate therapy, by country, 2007
    • Figure 104: Percentage of patients who terminate Remicade therapy In each time period
    • Figure 105: Percentage of inflammatory bowel disease patients terminating Remicade therapy within the first year because of each reason
    • Figure 106: Percentage of inflammatory bowel disease patients who fail Remicade therapy that are switched to each of the following therapy options, 2007
    • Figure 107: Humira' s attribute scores