Stakeholder Insight: Asthma - Over-prescribing is common in intermittent and mild forms of asthma

Introduction

Asthma is managed using a step-wise approach, with bronchodilators to relieve symptoms of airflow limitation and controller medications to target underlying inflammation. Datamonitor's research shows that almost all patients (even those with mild intermittent asthma) receive some type of controller medication as their baseline treatment, which is in line with international management guidelines.

Scope

*Patient segmentation with regards to disease severity, asthma phenotypes, co-morbidities and exacerbations

*Treatment choice split by line of therapy and disease severity

*Performance of asthma therapies in terms of factors such as efficacy, onset and duration of action, side effect profile, delivery method and cost

*Physician awareness and perception of drugs in development

Highlights

Recently, the classification of asthma has shifted to the concept of disease control in order to acknowledge the variability of the disease. Datamonitor research showed that around half of the physicians have taken on this new asthma classification, which may illustrate the transition away from the traditional severity classification.

The ICS class as a whole scored rather low on speed of onset, which may indicate an unmet need in this class. The traditional products Flixotide/Flovent (fluticasone) and Pulmicort (budesonide) scored consistently higher than the novel products Asmanex (mometasone) and Alvesco (ciclesonide).

Of the combination products in development, physicians were most aware of GSK's Beyond Advair, probably due to the fact that GSK already has had Advair/Seretide on the market. The other four ICS/LABA combinations were less well-known since they all come from companies without a current combination product on the market.

Reasons to Purchase

*Target physicians more effectively through an understanding of prescribing behavior and its influences.

*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.

ABOUT DATAMONITOR HEALTHCARE 2
About the Infectious Disease and Respiratory (ID&R) pharmaceutical analysis team 2
CHAPTER 1 EXECUTIVE SUMMARY 3
Scope of the analysis 3
Datamonitor insight into the asthma market 5
Contributing experts 6
Related reports 7
Upcoming related reports 7
CHAPTER 2 COUNTRY TREATMENT TREES 9
Introduction to treatment trees 9
US 10
5EU 12
Japan 14
France 16
Germany 18
Italy 20
Spain 22
UK 24
CHAPTER 3 PATIENT SEGMENTATION AND EPIDEMIOLOGY 26
Disease definition: the importance of inflammation 27
Asthma is caused by a combination of exogenous and genetic factors 27
Exogenous factors 28
Genetic factors 30
The role of airway inflammation, airway hyper-responsiveness and airway remodeling 31
Co-morbidities 35
Allergic rhinitis is the most common co-morbidity of asthma 35
Asthma and COPD can co-exist but true interaction between these diseases is unclear 36
Obesity may become even more important in the future of asthma 38
Disease classification - asthma control 39
Disease classification - asthma phenotypes 43
Allergic asthma is by far the most common phenotype 46
Asthma can be irreversible with chronic airflow obstruction 47
Awareness of nocturnal asthma as a phenotype may be low 48
Is exercise-induced asthma a separate phenotype? 49
Patients with steroid-resistant asthma have highest unmet needs 50
Why are phenotypes (not) used? 51
Asthma prevalence 53
Difference between physician's impression and publicized data is related to asthma definition 56
Asthma prevalence seems to be stabilizing 56
US 58
Japan 61
Europe 63
France 64
Germany 65
Italy 66
Spain 68
UK 69
CHAPTER 4 DIAGNOSIS AND DIAGNOSTIC TESTS 71
Presentation of asthma - symptoms 72
Diagnosis of asthma 72
Spirometry and PEF measurements are still underused 73
Allergen skin tests mostly used for initial diagnosis 75
Airway responsiveness challenges are mainly useful for difficult-to-diagnose patients 76
Upcoming diagnostic tests: sputum eosinophil count and fraction exhaled nitric oxide (FENO) 77
CHAPTER 5 TREATMENT OPTIONS AND TRENDS 79
Treatment options 80
Bronchodilators (relievers) 80
Beta2-agonists 80
Anticholinergics 81
Combination beta2-agonist/anticholinergic 82
Methyl xanthines 82
Anti-inflammatories (controllers) 83
Inhaled corticosteroids 83
Systemic corticosteroids 84
Non-steroidal anti-inflammatory drugs (NSAIDs) 84
ICS/LABA combinations 85
Biologicals 86
Inhaler device options 87
The ideal inhaler device 89
Treatment guidelines 91
The Global Initiative for Asthma (GINA) guidelines are most important international guidelines 92
The National Heart, Lung, and Blood Institute (NHLBI) guidelines follow GINA's focus on control 95
American Thoracic Society (ATS) and the European Respiratory Society (ERS) do not have specific asthma guidelines 97
National guidelines can supersede international guidelines 98
Most guidelines are now evidence-based 98
Treatment trends 101
Almost all patients receive some type of controller medication 102
Mild asthma is over-treated with long-term reliever medication 102
ICS/LABA combinations even used in mildest forms of asthma 103
Inhaled corticosteroids are less used as severity progresses 105
Long-acting bronchodilators mainly used in conjunction with an ICS 106
Antileukotriene drugs are especially popular in Japan 108
Short-acting bronchodilators is the most often used drug class in most severities 109
Theophylline is still prominent in Japanese treatment regimen 110
Omalizumab is reserved for the most severe asthma patients 111
CHAPTER 6 KEY PRESCRIBING INFLUENCES AND BRAND ASSESSMENT 114
Factors influencing physician decision making 115
Symptomatic improvement 116
Duration of action 119
Side-effect profile 121
Speed of onset 122
Recommended in treatment guidelines 124
Cost 125
Once-daily dosing 126
Flexible dosing 126
Device/mode of administration 127
Patient age 128
Physician perception of key products 129
Total scores per drug per country 131
Interpreting a brand map 133
The ICS/LABA combination class 135
The ICS/LABA combination products 136
The inhaled corticosteroid class 141
The inhaled corticosteroid products 142
The long-acting bronchodilator class 147
The long-acting bronchodilator products 148
The antileukotriene class 151
The antileukotriene products 152
Short-acting bronchodilators 153
Biologics - Xolair (omalizumab) 154
CHAPTER 7 TREATMENT OUTCOMES AND NEW PRODUCT DEVELOPMENT 157
Treatment outcomes 158
Unmet needs 160
Increase access to safe and effective immunotherapy 161
Improve therapeutic response by phenotyping 162
Reduce cost of medication 163
Reduce over-treatment of asthma 164
Develop ICS without side effects 165
Other unmet needs 166
New product development 167
Awareness of pipeline products 167
Combination products 167
LABAs and LAMAs 168
Novel mechanisms of action 169
Future use of pipeline products 170
Novel ICS/LABA combinations 171
Novel LABA/LAMA combinations 176
Novel LAMAs 177
Novel LABAs 179
Novel mechanisms of action 181
BIBLIOGRAPHY 185
Journal papers 185
Websites 204
Datamonitor reports 205
APPENDIX A 206
Physician research methodology 206
Physician sample breakdown 206
US 206
Japan 207
France 207
Germany 208
Italy 208
Spain 209
UK 209
Contributing experts 210
APPENDIX B 211
The survey questionnaire 211
Section 1 - Patient Segmentation 211
Section 2 - Diagnosis 215
Section 3 - Treatment 215
Section 4 - Treatment Outcomes 217
Section 5 - Product Profiles 218
Section 6 - Products in Development 223
APPENDIX C 226
About Datamonitor 226
About Datamonitor Healthcare 226
About the Infectious Disease and Respiratory (ID&R) analysis team 227
Disclaimer 228
List of Tables
Table 1: Percentage of physicians using each asthma classification system for each of the seven major markets, 2008 42
Table 2: Prevalence of adult asthma, by severity and country in the seven major markets, 2008 55
Table 3: Prevalence of asthma per country, according to Datamonitor's research among physicians and published literature, 2008 56
Table 4: Country totals for 12-month prevalence of asthma in both phases, average change per year and SE of the change by age, 2006 58
Table 5: Comparative analysis of the definition of the levels of evidence used in the asthma guidelines considered 100
Table 6: Primary endpoints of some of the ICS drugs used in asthma treatment 118
Table 7: Number and percentage of physicians able to rate each asthma drug, 2008 130
Table 8: Total scores (out of 100) of each asthma drug for each of the individual seven major markets 132
Table 9: Price differences between ICS/LABA* combination products in countries where Foster was available, 2007 138
Table 10: Price differences between ICS products in countries where all four products were available in 2007 145
Table 11: Mean percentage of asthma patients experiencing each number of exacerbations per year, by disease severity, across the seven major markets, 2008 159
Table 12: US physician sample breakdown, 2008 206
Table 13: Japan physician sample breakdown, 2008 207
Table 14: France physician sample breakdown, 2008 207
Table 15: Germany physician sample breakdown, 2008 208
Table 16: Italy physician sample breakdown, 2008 208
Table 17: Spain physician sample breakdown, 2008 209
Table 18: UK physician sample breakdown, 2008 209
Table 19: Percentage of all your current (diagnosed) asthma patients with each of the disease severities 212
Table 20: Classification that you primarily use to characterize your asthma patients 212
Table 21: Percentage of all your asthma patients presenting with each of the types of asthma 213
Table 22: Co-morbidities that your asthma patients present with and at which percentage 214
Table 23: Percentage of your asthma patients suffering from each number of exacerbations per year 214
Table 24: Percentage of all your current asthma patients receiving each of the following tests in order to facilitate diagnosis and track their status 215
Table 25: Percentage of all your current asthma patients receiving each of the following drug therapies as baseline therapy 216
Table 26: Relative importance of the factors when prescribing each of the drug classes for asthma 217
Table 27: Challenges in the management of asthma 218
Table 28: Rate of the performance or predicted performance of each of the ICS and ICS/LABA combinations 219
Table 29: Rate of the performance or predicted performance of each of the oral antileukotrienes and biologic 220
Table 30: Rate of the performance or predicted performance of each of the long-acting bronchodilators 221
Table 31: Points allocated to the importance of characteristics of a device 222
Table 32: Preference of device type per each drug class 222
Table 33: Awareness of pipeline products and how they would be prescribed 224
List of Figures
Figure 1: Diagrammatic overview of the coverage of the Stakeholder Insight: Asthma survey, 2008 4
Figure 2: US treatment tree (ICS/LABA combination and steroids), 2008 10
Figure 3: US treatment tree (others), 2008 11
Figure 4: 5EU treatment tree (ICS/LABA combination and steroids), 200 12
Figure 5: 5EU treatment tree (others), 2008 13
Figure 6: Japan treatment tree (ICS/LABA combination and steroids), 2008 14
Figure 7: Japan treatment tree (others), 2008 15
Figure 8: France treatment tree (ICS/LABA combination and steroids), 2008 16
Figure 9: France treatment tree (others), 2008 17
Figure 10: Germany treatment tree (ICS/LABA combination and steroids), 2008 18
Figure 11: Germany treatment tree (others), 2008 19
Figure 12: Italy treatment tree (ICS/LABA combination and steroids), 2008 20
Figure 13: Italy treatment tree (others), 2008 21
Figure 14: Spain treatment tree (ICS/LABA combination and steroids), 2008 22
Figure 15: Spain treatment tree (others), 2008 23
Figure 16: UK treatment tree (ICS/LABA combination and steroids), 2008 24
Figure 17: UK treatment tree (others), 2008 25
Figure 18: Effect of the interaction between various types of exposures and various genetic backgrounds through pathways involving atopy, airway inflammation, airway hyperresponsiveness (AHR) or other, unknown factors 34
Figure 19: Mean percentage of patients with each co-morbidity across the seven major markets, 2008 35
Figure 20: Levels of asthma control 40
Figure 21: Mean percentage of asthma patients with each asthma phenotype across the seven major markets, 2008 45
Figure 22: Familiarity with asthma phenotypes among physicians and their use in clinical practice, 2008 52
Figure 23: Severity of asthma as reported by physicians in the US (n=36) in the 2004 and 2008 Datamonitor surveys 60
Figure 24: Severity of asthma as reported by physicians in Japan (n=24) in the 2004 and 2008 Datamonitor surveys 62
Figure 25: Severity of asthma as reported by physicians in France (n=24) in the 2004 and 2008 Datamonitor surveys 64
Figure 26: Severity of asthma as reported by physicians in Germany (n=24) in the 2004 and 2008 Datamonitor surveys 65
Figure 27: Severity of asthma as reported by physicians in Italy (n=24) in the 2004 and 2008 Datamonitor surveys 67
Figure 28: Severity of asthma as reported by physicians in Spain (n=24) in the 2004 and 2008 Datamonitor surveys 68
Figure 29: Severity of asthma as reported by physicians in the UK (n=24) in the 2004 and 2008 Datamonitor surveys 70
Figure 30: Utilization per test for initial asthma diagnosis and to track a patient's disease status (n=180), 2008 75
Figure 31: Advantages and disadvantages of the main three types of portable inhaler devices 88
Figure 32: Relative importance of each inhaler device characteristic for treating asthma patients (n=180), 2008 89
Figure 33: Factors influencing inhaler choice 90
Figure 34: Percentage of physicians following each guideline, 2004 93
Figure 35: GINA asthma management approach based on control, 2007 guidelines 95
Figure 36: NHLBI asthma management approach, 2007 guidelines 97
Figure 37: The prescription of different drug classes for the treatment of asthma on average in the seven major markets, 2008 101
Figure 38: Overview of the prescription of controller medications across the seven major markets, per asthma severity, 2008 102
Figure 39: Overview of the prescription of reliever medications across the seven major markets, per asthma severity, 2008 103
Figure 40: Overview of the prescription of ICS/LABA combinations across asthma severities, per country, 2008 104
Figure 41: Overview of the prescription of ICS across asthma severities, per country, 2008 106
Figure 42: Overview of the prescription of long-acting bronchodilators across asthma severities, per country, 2008 107
Figure 43: Overview of the prescription of antileukotrienes across asthma severities, per country, 2008 108
Figure 44: Overview of the prescription of short-acting bronchodilators across asthma severities, per country, 2008 110
Figure 45: Overview of the prescription of theophylline across asthma severities, per country, 2008 111
Figure 46: Overview of the prescription of omalizumab across asthma severities, per country, 2008 113
Figure 47: Number of points allocated to each factor to indicate its relative importance when prescribing each class of asthma drugs, seven major markets, 2008 115
Figure 48: Number of points allocated to each factor (across asthma drug classes) to indicate its relative importance in each country or region, 2008 116
Figure 49: Proportion of 100 points distributed to reflect the importance of symptomatic improvement for each of the asthma drug classes, by country, 2008 117
Figure 50: Proportion of 100 points distributed to reflect the importance of duration of action for each of the asthma drug classes by country, 2008 119
Figure 51: The duration of action of formoterol and salmeterol 120
Figure 52: Proportion of 100 points distributed to reflect the importance of side-effect profiles for each of the asthma drug classes by country, 2008 121
Figure 53: Proportion of 100 points distributed to reflect the importance of speed of onset for each of the asthma drug classes by country, 2008 122
Figure 54: Efficacy of twice-daily 100µg fluticasone in adolescent and adult patients receiving bronchodilators alone 123
Figure 55: Proportion of 100 points distributed to reflect the importance of recommendations in guidelines for each of the asthma drug classes by country, 2008 124
Figure 56: Proportion of 100 points distributed to reflect the importance of costs for each of the asthma drug classes by country, 2008 125
Figure 57: Proportion of 100 points distributed to reflect the importance of once-daily dosing for each of the asthma drug classes by country, 2008 126
Figure 58: Proportion of 100 points distributed to reflect the importance of a flexible dosing for each of the asthma drug classes by country, 2008 127
Figure 59: Proportion of 100 points distributed to reflect the importance of the device/mode of administration for each of the asthma drug classes by country, 2008 128
Figure 60: Proportion of 100 points distributed to reflect the importance of patient age for each of the asthma drug classes by country, 2008 129
Figure 61: Brand map of the scoring attributes in relation to each other 134
Figure 62: Brand map of the scores of the individual products in relation to each other 135
Figure 63: Brand map highlighting the position of ICS/LABA combination products, 2008 136
Figure 64: Number of points allocated to each ICS/LABA combination product on all factors, seven major markets, 2008 137
Figure 65: Brand map highlighting the position of ICS products in the treatment of asthma, 2008 142
Figure 66: Number of points allocated to each ICS/LABA combination product on all factors, seven major markets, 2008 143
Figure 67: Brand map highlighting the position of long-acting bronchodilator products in the treatment of asthma, 2008 148
Figure 68: Number of points allocated to each long-acting bronchodilator product on all factors, seven major markets, 2008 149
Figure 69: Brand map highlighting the position of antileukotriene products in the treatment of asthma, 2008 151
Figure 70: Number of points allocated to each antileukotriene product on all factors, seven major markets, 2008 152
Figure 71: Brand map highlighting the position of biologic omalizumab in the treatment of asthma, 2008 155
Figure 72: Number of points allocated to Xolair on all factors, seven major markets, 2008 156
Figure 73: Rating of unmet needs in the management of asthma (n=180), 2008 161
Figure 74: The importance of increasing access to safe and effective immunotherapy, per country (n=180), 2008 162
Figure 75: The importance of improving therapeutic response by phenotyping, per country (n=180), 2008 163
Figure 76: The importance of reducing the cost of medication, per country (n=180), 2008 164
Figure 77: The importance of reducing over-treatment of asthma patients, per country (n=180), 2008 165
Figure 78: The importance of developing an ICS without side effects, per country (n=180), 2008 166
Figure 79: Level of awareness of novel ICS/LABA and LABA/LAMA combinations in each individual country, seven major markets, 2008 168
Figure 80: Level of awareness of novel LABAs and LAMAs in each individual country, seven major markets, 2008 169
Figure 81: Level of awareness of novel mechanisms in each individual country , seven major markets, 2008 170
Figure 82: Questions regarding pipeline asthma products, 2008 171
Figure 83: Future use of once-daily ICS/LABA combination pipeline products 173
Figure 84: Future use of me-too ICS/LABA combination pipeline products 175
Figure 85: Future use of LABA/LAMA combination pipeline products 177
Figure 86: Future use of LAMA pipeline products 179
Figure 87: Future use of LABA pipeline products 181
Figure 88: Future use of new mechanisms in asthma treatment, 2008 183
Figure 89: Severities of asthma 211