Market Report Source

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

Report 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 150