COPD what s new

1. COPD � what�s new? Jay Suntharalingam Consultant Respiratory Physician

2. What�s new in COPD? Large RCTs (eg TORCH & UPLIFT) NICE update 2010 National Clinical Strategy New licensed drugs diagnosis latest guidance on inhaler therapy

3. COPD � the scale of the problem common � 900,000 diagnosed with COPD 70% of people with COPD in the UK are undiagnosed COPD patients often diagnosed late UK mortality compares unfavourably with Europe

4. COPD � natural history This diagram shows that lung damage is likely to have happened before airflow obstruction is detectable by spirometry (the red line). Before this point there are the well population and those who are at risk, some of whom may already have early lung damage. For the well population we need to focus on raising awareness of the early signs and symptoms of COPD, and link with other disease areas such as lung cancer and coronary heart disease, which are common co-morbidites. For those at risk, we need to raise awareness of the risk factors, for example smoking and occupational and environmental hazards. Links also need to be made with employers and clarify their roles around identifying people who may be at risk of COPD and enabling them to reduce their risk factors. This diagram shows that lung damage is likely to have happened before airflow obstruction is detectable by spirometry (the red line). Before this point there are the well population and those who are at risk, some of whom may already have early lung damage. For the well population we need to focus on raising awareness of the early signs and symptoms of COPD, and link with other disease areas such as lung cancer and coronary heart disease, which are common co-morbidites. For those at risk, we need to raise awareness of the risk factors, for example smoking and occupational and environmental hazards. Links also need to be made with employers and clarify their roles around identifying people who may be at risk of COPD and enabling them to reduce their risk factors.

5. Prevention and awareness This diagram shows that lung damage is likely to have happened before airflow obstruction is detectable by spirometry (the red line). Before this point there are the well population and those who are at risk, some of whom may already have early lung damage. For the well population we need to focus on raising awareness of the early signs and symptoms of COPD, and link with other disease areas such as lung cancer and coronary heart disease, which are common co-morbidites. For those at risk, we need to raise awareness of the risk factors, for example smoking and occupational and environmental hazards. Links also need to be made with employers and clarify their roles around identifying people who may be at risk of COPD and enabling them to reduce their risk factors. This diagram shows that lung damage is likely to have happened before airflow obstruction is detectable by spirometry (the red line). Before this point there are the well population and those who are at risk, some of whom may already have early lung damage. For the well population we need to focus on raising awareness of the early signs and symptoms of COPD, and link with other disease areas such as lung cancer and coronary heart disease, which are common co-morbidites. For those at risk, we need to raise awareness of the risk factors, for example smoking and occupational and environmental hazards. Links also need to be made with employers and clarify their roles around identifying people who may be at risk of COPD and enabling them to reduce their risk factors.

6. Screening, detection anddiagnosis For those with mild COPD the emphasis will be on: Improving diagnostic accuracy Identifying how best to find cases of COPD, which could be through targeted case finding, for example smokers over 40, or through more widespread population screening.For those with mild COPD the emphasis will be on: Improving diagnostic accuracy Identifying how best to find cases of COPD, which could be through targeted case finding, for example smokers over 40, or through more widespread population screening.

7. Case 1 64 year old man no prior respiratory history ex smoker - 30 pack year history 12 months of worsening exertional dyspnoea associated cough

8. Case 1

9. Case 2 51 year old man ex smoker - 15 pack year history 6 months of worsening exertional dyspnoea �screening� spirometry at local supermarket

10. Case 2

11. Case 2

12. Misdiagnoses of COPD are common A study of registered �COPD� patients in Devon found that repeat assessment showed COPD 68.5% COPD with asthma 4.3% Asthma 6.7% Restrictive disorder 4.0% Cardiac 0.3% Normal 16.2%

13. Screening, detection anddiagnosis For those with mild COPD the emphasis will be on: Improving diagnostic accuracy Identifying how best to find cases of COPD, which could be through targeted case finding, for example smokers over 40, or through more widespread population screening.For those with mild COPD the emphasis will be on: Improving diagnostic accuracy Identifying how best to find cases of COPD, which could be through targeted case finding, for example smokers over 40, or through more widespread population screening.

14. Chronic care For those people with a diagnosis of COPD, we will recommend that everyone has A comprehensive care plan A self-management plan Up to date disease registers, stratified by severity, that can be used to proactively manage patients, so that those with mild disease are reviewed at least annually, moderate six monthly and severe quarterly.For those people with a diagnosis of COPD, we will recommend that everyone has A comprehensive care plan A self-management plan Up to date disease registers, stratified by severity, that can be used to proactively manage patients, so that those with mild disease are reviewed at least annually, moderate six monthly and severe quarterly.

15. Medicines, devices and interventions There are various treatments and devices that are appropriate at different stages of the disease. For example, at the mild stages the recommendations will focus on advice on healthy lifestyles, educating patients about their condition, helping them remain in work, and providing stop smoking support. For those at the moderate stage, access to pulmonary rehab will be improved. At the severe stage, this will be built upon with more specialist interventions that may become appropriate, for example assessing for arterial hypoxaemia. At every stage of the disease there will be: Regular review of psychological needs Referral for nutritional input where appropriate Regular assessment for appropriateness of surgical Interventions Regular assessment for aids and devices to improve activities of daily living Specialist assessment for need to oxygen therapy There are various treatments and devices that are appropriate at different stages of the disease. For example, at the mild stages the recommendations will focus on advice on healthy lifestyles, educating patients about their condition, helping them remain in work, and providing stop smoking support. For those at the moderate stage, access to pulmonary rehab will be improved. At the severe stage, this will be built upon with more specialist interventions that may become appropriate, for example assessing for arterial hypoxaemia. At every stage of the disease there will be: Regular review of psychological needs Referral for nutritional input where appropriate Regular assessment for appropriateness of surgical Interventions Regular assessment for aids and devices to improve activities of daily living Specialist assessment for need to oxygen therapy

17. This provides a summary of the recommended treatment at each stage of COPD. This provides a summary of the recommended treatment at each stage of COPD.

18. COPD � NICE 2004

19. NICE - a holistic approach

20. NICE - a holistic approach

21. Breathlessness and exercise limitation (NICE 2004) use short acting bronchodilator try combined therapy with short acting �2-agonist and short acting anticholinergic try a long acting bronchodilator try combined LABA and ICS consider theophylline add on therapy pulmonary rehabilitation surgery BTS guidelines used to say look at reversibility testing and then be guided by that � rubbish Consider trying all these in turn, looking at symptoms, quality of life and lung function � any improvement in any one of these after a four week period justifies continuing with the drug BTS guidelines used to say look at reversibility testing and then be guided by that � rubbish Consider trying all these in turn, looking at symptoms, quality of life and lung function � any improvement in any one of these after a four week period justifies continuing with the drug

22. Frequent exacerbations

23. Frequent exacerbations (NICE 2004) pneumococcal and annual influenza vaccines optimise bronchodilator therapy with one or more long-acting bronchodilators add inhaled corticosteroids if FEV1<50% and 2 or more exacerbations in 12 months

24. What�s changed since 2004? Combivent inhaler withdrawn Large RCTs published � TORCH and UPLIFT

25. TORCH TOwards a Revolution in COPD Health Looking to the future for COPD patients

26. TORCH: main objectives Primary objective The effect of SeretideTM 500 AccuhalerTM vs control on all-cause mortality over 3 years in patients with moderate-to-severe COPD Secondary objectives The effect of SeretideTM 500 AccuhalerTM on the rate of moderate and severe exacerbations over 3 years The effect of SeretideTM 500 AccuhalerTM on health status (SGRQ) over 3 years Post-bronchodilator FEV1 Notes: The primary endpoint of the TORCH trial1 was the effect of Seretide � 500 Accuhaler � combination versus control on all-cause mortality over 3 years in patients with moderate-to-severe COPD. All-cause mortality was chosen as the primary endpoint because it is important to ensure that treatment is not reducing mortality from one cause, while increasing mortality from another. This makes all-cause mortality a more robust endpoint than looking for one single cause of death. COPD is a multicomponent disease and patients die from causes other than COPD, including lung cancer, heart disease and stroke.2 Additionally, all-cause mortality is not dependent on coding practice, which can differ between countries, and it can be very difficult to reliably differentiate between death due to COPD specifically and that where COPD was a contributing factor. Patients who withdrew prematurely from the study were also followed-up with regular contact for 3 years from the date of randomisation in order to determine survival status. Secondary endpoints of the TORCH trial were: COPD morbidity as measured by the rate of exacerbations Health-related quality of life (HRQoL) as measured by the St. George�s Respiratory Questionnaire (SGRQ) at 24-weekly intervals. References 1. Vestbo J, TORCH Study Group. The TORCH (TOwards a Revolution in COPD Health) survival study protocol. Eur Respir J 2004;24:206�10. 2. Sin DD, Anthonisen NR, Soriano JB, Agusti AG. Mortality in COPD: role of comorbidities. Eur Respir J 2006; accepted.Notes: The primary endpoint of the TORCH trial1 was the effect of Seretide � 500 Accuhaler � combination versus control on all-cause mortality over 3 years in patients with moderate-to-severe COPD. All-cause mortality was chosen as the primary endpoint because it is important to ensure that treatment is not reducing mortality from one cause, while increasing mortality from another. This makes all-cause mortality a more robust endpoint than looking for one single cause of death. COPD is a multicomponent disease and patients die from causes other than COPD, including lung cancer, heart disease and stroke.2 Additionally, all-cause mortality is not dependent on coding practice, which can differ between countries, and it can be very difficult to reliably differentiate between death due to COPD specifically and that where COPD was a contributing factor. Patients who withdrew prematurely from the study were also followed-up with regular contact for 3 years from the date of randomisation in order to determine survival status. Secondary endpoints of the TORCH trial were: COPD morbidity as measured by the rate of exacerbations Health-related quality of life (HRQoL) as measured by the St. George�s Respiratory Questionnaire (SGRQ) at 24-weekly intervals. References 1. Vestbo J, TORCH Study Group. The TORCH (TOwards a Revolution in COPD Health) survival study protocol. Eur Respir J 2004;24:206�10. 2. Sin DD, Anthonisen NR, Soriano JB, Agusti AG. Mortality in COPD: role of comorbidities. Eur Respir J 2006; accepted.

27. TORCH: study design Notes: TOwards a Revolution in COPD Health (TORCH) is a 3-year, international, multicentre, controlled, double-blind, randomised, parallel group trial1 The first patient was recruited in 2000, with results becoming available in 2006. Patients with moderate to severe COPD were recruited. The inclusion criteria for patients in TORCH were: age 40�80 years, an established clinical history of COPD, a smoking history of ?10 pack years, baseline forced expiratory volume in one second (FEV1) <60% predicted (pre-bronchodilator), <10% reversibility in predicted FEV1 and a FEV1/forced vital capacity (FVC) ratio ?70%. The study design included a 2-week run-in period, a 3-year treatment phase and a2-week follow-up phase. Patients were randomised to one of the following four treatment groups, all administered twice daily via the Accuhaler� dry powder inhaler device: Control Salmeterol 50 mcg � a long-acting �2-agonist Fluticasone propionate 500 mcg � an inhaled corticosteroid Seretide � 500 Accuhaler � All medications for conditions other than COPD were permitted during the study. The UK licence for Seretide is for patients with <50% FEV1. To comply with the licence it is necessary for the data to be re analysed for the <50% patient population. This equated to 74% of the patients2 TORCH was an intent-to-treat study. This means that if patients did not fully comply with their study medication, or did not take any, they are still counted in the original group to which they were allocated. For a trial to be truly randomised, you must ensure that all patients in the groups to which they were randomised are analysed, otherwise you may favour some groups over others in the results. Note: FP is not licensed as monotherapy in COPD Reference Vestbo J, TORCH Study Group. The TORCH (TOwards a Revolution in COPD Health) survival study protocol. Eur Respir J 2004;24:206�10. GSK Data on File SERTCODOF012 Notes: TOwards a Revolution in COPD Health (TORCH) is a 3-year, international, multicentre, controlled, double-blind, randomised, parallel group trial1 The first patient was recruited in 2000, with results becoming available in 2006. Patients with moderate to severe COPD were recruited. The inclusion criteria for patients in TORCH were: age 40�80 years, an established clinical history of COPD, a smoking history of ?10 pack years, baseline forced expiratory volume in one second (FEV1) <60% predicted (pre-bronchodilator), <10% reversibility in predicted FEV1 and a FEV1/forced vital capacity (FVC) ratio ?70%. The study design included a 2-week run-in period, a 3-year treatment phase and a2-week follow-up phase. Patients were randomised to one of the following four treatment groups, all administered twice daily via the Accuhaler� dry powder inhaler device: Control Salmeterol 50 mcg � a long-acting �2-agonist Fluticasone propionate 500 mcg � an inhaled corticosteroid Seretide � 500 Accuhaler � All medications for conditions other than COPD were permitted during the study. The UK licence for Seretide is for patients with <50% FEV1. To comply with the licence it is necessary for the data to be re analysed for the <50% patient population. This equated to 74% of the patients2 TORCH was an intent-to-treat study. This means that if patients did not fully comply with their study medication, or did not take any, they are still counted in the original group to which they were allocated. For a trial to be truly randomised, you must ensure that all patients in the groups to which they were randomised are analysed, otherwise you may favour some groups over others in the results. Note: FP is not licensed as monotherapy in COPD Reference Vestbo J, TORCH Study Group. The TORCH (TOwards a Revolution in COPD Health) survival study protocol. Eur Respir J 2004;24:206�10. GSK Data on File SERTCODOF012

28. TORCH: results SeretideTM 500 Accuhaler TM reduced the risk of all-cause mortality by 17.5% versus control. This was non-statistically significant (p=0.052) Notes: The survival status of 6111/6112 patients was established. One subject in the Seretide � 500 Accuhaler � arm with survival status unknown at 3 years was treated as censored at 2 years (113 weeks) (the last time point at which survival status was known). The difference in all-cause mortality between Seretide � 500 Accuhaler � and control was analysed by the log-rank test (stratified by smoking status) and presented as a Kaplan-Meier plot (note the plot shown above is Cumulative Incidence which is 100 - Kaplan Meier). The HR was also calculated. There was a 17.5% reduction in the risk of mortality at any time during the 3 years for Seretide � 500 Accuhaler � vs control which was not statistically significant The primary endpoint in TORCH was the reduction in all-cause mortality between Seretide � 500 Accuhaler � and control. References: Salmeterol and Fluticasone Propionate and Survival in Chronic Obstructive Pulmonary Disease Calverley P. M.A., Anderson J. A., Celli B., Ferguson G. T., Jenkins C., Jones P. W., Yates J. C., Vestbo J., the TORCH investigators N Engl J Med 2007; 356:775-789, February 22, 2007 Notes: The survival status of 6111/6112 patients was established. One subject in the Seretide � 500 Accuhaler � arm with survival status unknown at 3 years was treated as censored at 2 years (113 weeks) (the last time point at which survival status was known). The difference in all-cause mortality between Seretide � 500 Accuhaler � and control was analysed by the log-rank test (stratified by smoking status) and presented as a Kaplan-Meier plot (note the plot shown above is Cumulative Incidence which is 100 - Kaplan Meier). The HR was also calculated. There was a 17.5% reduction in the risk of mortality at any time during the 3 years for Seretide � 500 Accuhaler � vs control which was not statistically significant The primary endpoint in TORCH was the reduction in all-cause mortality between Seretide � 500 Accuhaler � and control. References: Salmeterol and Fluticasone Propionate and Survival in Chronic Obstructive Pulmonary Disease Calverley P. M.A., Anderson J. A., Celli B., Ferguson G. T., Jenkins C., Jones P. W., Yates J. C., Vestbo J., the TORCH investigators N Engl J Med 2007; 356:775-789, February 22, 2007

29. TORCH - survival data

30. TORCH: results SeretideTM 500 Accuhaler TM reduced the risk of all-cause mortality by 17.5% versus control. This was non-statistically significant (p=0.052) SeretideTM 500 Accuhaler TM improved and maintained health status versus control over 3 years (p<0.001) Notes: The survival status of 6111/6112 patients was established. One subject in the Seretide � 500 Accuhaler � arm with survival status unknown at 3 years was treated as censored at 2 years (113 weeks) (the last time point at which survival status was known). The difference in all-cause mortality between Seretide � 500 Accuhaler � and control was analysed by the log-rank test (stratified by smoking status) and presented as a Kaplan-Meier plot (note the plot shown above is Cumulative Incidence which is 100 - Kaplan Meier). The HR was also calculated. There was a 17.5% reduction in the risk of mortality at any time during the 3 years for Seretide � 500 Accuhaler � vs control which was not statistically significant The primary endpoint in TORCH was the reduction in all-cause mortality between Seretide � 500 Accuhaler � and control. References: Salmeterol and Fluticasone Propionate and Survival in Chronic Obstructive Pulmonary Disease Calverley P. M.A., Anderson J. A., Celli B., Ferguson G. T., Jenkins C., Jones P. W., Yates J. C., Vestbo J., the TORCH investigators N Engl J Med 2007; 356:775-789, February 22, 2007 Notes: The survival status of 6111/6112 patients was established. One subject in the Seretide � 500 Accuhaler � arm with survival status unknown at 3 years was treated as censored at 2 years (113 weeks) (the last time point at which survival status was known). The difference in all-cause mortality between Seretide � 500 Accuhaler � and control was analysed by the log-rank test (stratified by smoking status) and presented as a Kaplan-Meier plot (note the plot shown above is Cumulative Incidence which is 100 - Kaplan Meier). The HR was also calculated. There was a 17.5% reduction in the risk of mortality at any time during the 3 years for Seretide � 500 Accuhaler � vs control which was not statistically significant The primary endpoint in TORCH was the reduction in all-cause mortality between Seretide � 500 Accuhaler � and control. References: Salmeterol and Fluticasone Propionate and Survival in Chronic Obstructive Pulmonary Disease Calverley P. M.A., Anderson J. A., Celli B., Ferguson G. T., Jenkins C., Jones P. W., Yates J. C., Vestbo J., the TORCH investigators N Engl J Med 2007; 356:775-789, February 22, 2007

31. TORCH: results - health status

32. TORCH: results SeretideTM 500 Accuhaler TM reduced the risk of all-cause mortality by 17.5% versus control. This was non-statistically significant (p=0.052) SeretideTM 500 Accuhaler TM improved and maintained health status versus control over 3 years (p<0.001) SeretideTM 500 Accuhaler TM improved and maintained lung function versus control over 3 years (p<0.001) Notes: The survival status of 6111/6112 patients was established. One subject in the Seretide � 500 Accuhaler � arm with survival status unknown at 3 years was treated as censored at 2 years (113 weeks) (the last time point at which survival status was known). The difference in all-cause mortality between Seretide � 500 Accuhaler � and control was analysed by the log-rank test (stratified by smoking status) and presented as a Kaplan-Meier plot (note the plot shown above is Cumulative Incidence which is 100 - Kaplan Meier). The HR was also calculated. There was a 17.5% reduction in the risk of mortality at any time during the 3 years for Seretide � 500 Accuhaler � vs control which was not statistically significant The primary endpoint in TORCH was the reduction in all-cause mortality between Seretide � 500 Accuhaler � and control. References: Salmeterol and Fluticasone Propionate and Survival in Chronic Obstructive Pulmonary Disease Calverley P. M.A., Anderson J. A., Celli B., Ferguson G. T., Jenkins C., Jones P. W., Yates J. C., Vestbo J., the TORCH investigators N Engl J Med 2007; 356:775-789, February 22, 2007 Notes: The survival status of 6111/6112 patients was established. One subject in the Seretide � 500 Accuhaler � arm with survival status unknown at 3 years was treated as censored at 2 years (113 weeks) (the last time point at which survival status was known). The difference in all-cause mortality between Seretide � 500 Accuhaler � and control was analysed by the log-rank test (stratified by smoking status) and presented as a Kaplan-Meier plot (note the plot shown above is Cumulative Incidence which is 100 - Kaplan Meier). The HR was also calculated. There was a 17.5% reduction in the risk of mortality at any time during the 3 years for Seretide � 500 Accuhaler � vs control which was not statistically significant The primary endpoint in TORCH was the reduction in all-cause mortality between Seretide � 500 Accuhaler � and control. References: Salmeterol and Fluticasone Propionate and Survival in Chronic Obstructive Pulmonary Disease Calverley P. M.A., Anderson J. A., Celli B., Ferguson G. T., Jenkins C., Jones P. W., Yates J. C., Vestbo J., the TORCH investigators N Engl J Med 2007; 356:775-789, February 22, 2007

33. TORCH: results - FEV1

34. TORCH: results SeretideTM 500 Accuhaler TM reduced the risk of all-cause mortality by 17.5% versus control. This was non-statistically significant (p=0.052) SeretideTM 500 Accuhaler TM improved and maintained health status versus control over 3 years (p<0.001) SeretideTM 500 Accuhaler TM improved and maintained lung function versus control over 3 years (p<0.001) SeretideTM 500 Accuhaler TM reduced exacerbations requiring oral corticosteroids by 43% vs control over 3 years (p<0.001) Notes: The survival status of 6111/6112 patients was established. One subject in the Seretide � 500 Accuhaler � arm with survival status unknown at 3 years was treated as censored at 2 years (113 weeks) (the last time point at which survival status was known). The difference in all-cause mortality between Seretide � 500 Accuhaler � and control was analysed by the log-rank test (stratified by smoking status) and presented as a Kaplan-Meier plot (note the plot shown above is Cumulative Incidence which is 100 - Kaplan Meier). The HR was also calculated. There was a 17.5% reduction in the risk of mortality at any time during the 3 years for Seretide � 500 Accuhaler � vs control which was not statistically significant The primary endpoint in TORCH was the reduction in all-cause mortality between Seretide � 500 Accuhaler � and control. References: Salmeterol and Fluticasone Propionate and Survival in Chronic Obstructive Pulmonary Disease Calverley P. M.A., Anderson J. A., Celli B., Ferguson G. T., Jenkins C., Jones P. W., Yates J. C., Vestbo J., the TORCH investigators N Engl J Med 2007; 356:775-789, February 22, 2007 Notes: The survival status of 6111/6112 patients was established. One subject in the Seretide � 500 Accuhaler � arm with survival status unknown at 3 years was treated as censored at 2 years (113 weeks) (the last time point at which survival status was known). The difference in all-cause mortality between Seretide � 500 Accuhaler � and control was analysed by the log-rank test (stratified by smoking status) and presented as a Kaplan-Meier plot (note the plot shown above is Cumulative Incidence which is 100 - Kaplan Meier). The HR was also calculated. There was a 17.5% reduction in the risk of mortality at any time during the 3 years for Seretide � 500 Accuhaler � vs control which was not statistically significant The primary endpoint in TORCH was the reduction in all-cause mortality between Seretide � 500 Accuhaler � and control. References: Salmeterol and Fluticasone Propionate and Survival in Chronic Obstructive Pulmonary Disease Calverley P. M.A., Anderson J. A., Celli B., Ferguson G. T., Jenkins C., Jones P. W., Yates J. C., Vestbo J., the TORCH investigators N Engl J Med 2007; 356:775-789, February 22, 2007

35. TORCH: results - exacerbations

36. COPD - morbidity

37. UPLIFT

38. UPLIFT Primary objective: Assess whether tiotropium 18�g once daily is associated with a decrease in the rate of decline of FEV1 over time in patients with COPD Secondary objectives: quality of life mortality (respiratory and all-cause) exacerbations hospitalisations

39. Study Design Key points INSPIRE compared SFC and TIO over 2 years A 2- week treatment optimisation phase was included INSPIRE was a 2-year, multicentre, multinational, double-blind, double-dummy randomised, parallel group study comparing Seretide with tiotropium. 1,323 patients were randomised into the trial, 658 on Seretide and 665 on tiotropium. All patients entered a treatment optimisation phase to optimise their condition. Patients discontinued their current medication and were given 30mg oral corticosteroid once daily plus salmeterol 50mg twice daily for two weeks. At the end of this period patients were randomised to either Seretide (salmeterol/fluticasone propionate SFC) 50/500mg b.d. or tiotropium 18mg o.d. for 2 years.1 Research suggests that an optimisation phase may have benefits for studies compared with withdrawing maintenance therapy during run-in. In particular, it may improve detection of clinically important changes in health status, and reduce the proportion of withdrawals during the run-in. There is a precedent for this study design. Calverley has previously optimised patients with prednisolone and formoterol before randomisation to treatment2. 1. Seemungal TA, Stockley Rm Calverley PM, Hagan G, Wedzicha JA. Investigating New Standards for Prophylaxis in Reduction of Exacerbations � The INSPIRE study methodology. J. COPD 2007; 4 (3): 173 - 184 2. Calverley P, Boonsawat W, Cseke Z, et al. Maintenance therapy with budesonide and formoterol in chronic obstructive pulmonary disease. Eur Respir J 2003; 22:912-919 Key points INSPIRE compared SFC and TIO over 2 years A 2- week treatment optimisation phase was included INSPIRE was a 2-year, multicentre, multinational, double-blind, double-dummy randomised, parallel group study comparing Seretide with tiotropium. 1,323 patients were randomised into the trial, 658 on Seretide and 665 on tiotropium. All patients entered a treatment optimisation phase to optimise their condition. Patients discontinued their current medication and were given 30mg oral corticosteroid once daily plus salmeterol 50mg twice daily for two weeks. At the end of this period patients were randomised to either Seretide (salmeterol/fluticasone propionate SFC) 50/500mg b.d. or tiotropium 18mg o.d. for 2 years.1 Research suggests that an optimisation phase may have benefits for studies compared with withdrawing maintenance therapy during run-in. In particular, it may improve detection of clinically important changes in health status, and reduce the proportion of withdrawals during the run-in. There is a precedent for this study design. Calverley has previously optimised patients with prednisolone and formoterol before randomisation to treatment2. 1. Seemungal TA, Stockley Rm Calverley PM, Hagan G, Wedzicha JA. Investigating New Standards for Prophylaxis in Reduction of Exacerbations � The INSPIRE study methodology. J. COPD 2007; 4 (3): 173 - 184 2. Calverley P, Boonsawat W, Cseke Z, et al. Maintenance therapy with budesonide and formoterol in chronic obstructive pulmonary disease. Eur Respir J 2003; 22:912-919

40. Baseline and on-treatment medications

41. Study Design Key points INSPIRE compared SFC and TIO over 2 years A 2- week treatment optimisation phase was included INSPIRE was a 2-year, multicentre, multinational, double-blind, double-dummy randomised, parallel group study comparing Seretide with tiotropium. 1,323 patients were randomised into the trial, 658 on Seretide and 665 on tiotropium. All patients entered a treatment optimisation phase to optimise their condition. Patients discontinued their current medication and were given 30mg oral corticosteroid once daily plus salmeterol 50mg twice daily for two weeks. At the end of this period patients were randomised to either Seretide (salmeterol/fluticasone propionate SFC) 50/500mg b.d. or tiotropium 18mg o.d. for 2 years.1 Research suggests that an optimisation phase may have benefits for studies compared with withdrawing maintenance therapy during run-in. In particular, it may improve detection of clinically important changes in health status, and reduce the proportion of withdrawals during the run-in. There is a precedent for this study design. Calverley has previously optimised patients with prednisolone and formoterol before randomisation to treatment2. 1. Seemungal TA, Stockley Rm Calverley PM, Hagan G, Wedzicha JA. Investigating New Standards for Prophylaxis in Reduction of Exacerbations � The INSPIRE study methodology. J. COPD 2007; 4 (3): 173 - 184 2. Calverley P, Boonsawat W, Cseke Z, et al. Maintenance therapy with budesonide and formoterol in chronic obstructive pulmonary disease. Eur Respir J 2003; 22:912-919 Key points INSPIRE compared SFC and TIO over 2 years A 2- week treatment optimisation phase was included INSPIRE was a 2-year, multicentre, multinational, double-blind, double-dummy randomised, parallel group study comparing Seretide with tiotropium. 1,323 patients were randomised into the trial, 658 on Seretide and 665 on tiotropium. All patients entered a treatment optimisation phase to optimise their condition. Patients discontinued their current medication and were given 30mg oral corticosteroid once daily plus salmeterol 50mg twice daily for two weeks. At the end of this period patients were randomised to either Seretide (salmeterol/fluticasone propionate SFC) 50/500mg b.d. or tiotropium 18mg o.d. for 2 years.1 Research suggests that an optimisation phase may have benefits for studies compared with withdrawing maintenance therapy during run-in. In particular, it may improve detection of clinically important changes in health status, and reduce the proportion of withdrawals during the run-in. There is a precedent for this study design. Calverley has previously optimised patients with prednisolone and formoterol before randomisation to treatment2. 1. Seemungal TA, Stockley Rm Calverley PM, Hagan G, Wedzicha JA. Investigating New Standards for Prophylaxis in Reduction of Exacerbations � The INSPIRE study methodology. J. COPD 2007; 4 (3): 173 - 184 2. Calverley P, Boonsawat W, Cseke Z, et al. Maintenance therapy with budesonide and formoterol in chronic obstructive pulmonary disease. Eur Respir J 2003; 22:912-919

42. No difference in rate of decline of FEV1

43. Risk of COPD exacerbations vs. control

44. Sustained improvements in HRQoL over 4 years vs. control

45. Major trials in COPD TORCH UPLIFT

46. NICE algorithm 2010

47. Choosing inhaler therapy

48. Take home points

49. Take home points An accurate and early diagnosis of COPD is crucial

50. Take home points An accurate and early diagnosis of COPD is crucial Greater emphasis on health promotion and disease prevention

51. Take home points An accurate and early diagnosis of COPD is crucial Greater emphasis on health promotion and disease prevention Inhaler therapy guidelines have been updated

52. 2nd Annual Respiratory Study Day Bailbrook House Wednesday 15th June 2011

53. Topics COPD update Interstitial lung disease Infection and the lung Asbestos related lung disease Respiratory Medicine in the Elderly Thoracic surgery Asthma update Workshops � lung cancer, spirometry, cases and respiratory nurse interventions

54. Any questions?