Property of Presenter COPD. BARRY MAKE, MD Co-Director, COPD Program. Director, Pulmonary Rehabilitation National Jewish Health, Denver, CO

Transcription

1 COPD BARRY MAKE, MD Co-Director, COPD Program. Director, Pulmonary Rehabilitation National Jewish Health, Denver, CO

2 Question #1 Which photo do you like? 1. COPD patient carrying oxygen on his bicycle 2. Lilly pond at 9,000 feet elevation 3. Lions, tigers and BEARS

3 Disclosure Information Advisory board, consultant, multi-center trial, research funding or speaker in the last year for topics related to COPD: National Heart, Lung, and Blood Institute AstraZeneca Boehringer-Ingelheim CSL Bering Forest GlaxoSmithKline Novartis Spiration Sunovion Theravance January, 2015

4 Objectives Discuss a recent article on reducing therapy for COPD exacerbations the Wisdom trial Understand the importance of COPD exacerbations Know what therapies reduce COPD exacerbations

5 Session Methodology DISCUSSION Participation by all who are interested Audience response system Focus on a recent publication in New England Journal of Medicine Your feedback is encouraged

6 Question #2 Did you complete the assignment: Read New Engl J of Med WISDOM Trial? 1. No 2. Yes 3. Other

7 Question #3 What percentage of your patients with COPD are on triple therapy? - long-acting antimuscarinic antagonist (tiotropium, aclidinium, etc), - long-acting beta-agonist / inhaled steroid (salmeterol / fluticasone, formoterol / budesonide, etc) 1. 10% 24% 2. 25% - 50% 3. 51% - 74% 4. 75% - 100%

8 Question #4 Why are MOST of YOUR COPD patients on triple therapy? 1. AECOPD are financially costly 2. AECOPD reduce lung function 3. Therapies can reduce AECOPD 4. Self-management programs always reduce AECOPD 5. All (1 4) are correct

9 Question #5 COPD exacerbation importance: Which are NOT correct? 1. AECOPD are financially costly 2. AECOPD reduce lung function 3. Therapies can reduce AECOPD 4. Self-management programs always reduce AECOPD 5. All (1 4) are correct

10 Goals of COPD Management Relieve symptoms (SOB) Improve exercise tolerance Improve health status Prevent disease progression Prevent and treat exacerbations Reduce mortality Reduce symptoms Reduce risk Global Initiative for Chronic Obstructive Lung Disease. Global strategy of the diagnosis, management, and prevention of COPD

11 Long-acting Bronchodilator Effects Relieve symptoms (SOB) Improve exercise tolerance Improve health status Prevent disease progression Prevent and treat exacerbations Reduce mortality Reduce symptoms Reduce risk Global Initiative for Chronic Obstructive Lung Disease. Global strategy of the diagnosis, management, and prevention of COPD

12 Question #6 Do these medications reduce COPD exacerbations? Long-acting muscarinic antagonists Inhaled steroid / long-acting beta agonist combination 1. YES 2. NO 3. NOT SURE

13 Understanding Potential Long-Term Impacts on Function with Tiotropium (UPLIFT)

14 Tiotropium Reduces Exacerbations Probability of exacerbation (%) Tiotropium Placebo Months 14% reduction in exacerbation when added to usual therapy HR=0.86 (0.81, 0.91) P<0.001 (log-rank test) HR = Hazard ratio (95% confidence intervals) Tashkin DP, et al. N Engl J Med. 2008;359:

15 UPLIFT: AECOPD In Moderate COPD Decramer M, et al. Lancet, 2009; 374,

16 Hazard ratio, 0.83 (95% CI, ) P <0.001 by log-rank test

17 Bronchodilators: Potential Mechanisms for Preventing Exacerbations Lung deflation - assists lung emptying Improved respiratory muscle function Less dyspnea More tolerant of increased symptoms Less static and dynamic hyperinflation Improvement in hyperinflation correlates better with improvements in exacerbation frequency than does FEV 1

18 Bronchodilators: Potential Mechanisms for Preventing Exacerbations Lung deflation - assists lung emptying Decreased lung inflammation Hyperinflation is pro-inflammatory Anti-viral effects Improved clearance of respiratory secretions

19 Long-Acting β 2 -Agonist + Corticosteroid: COPD Exacerbation Frequency (TORCH) Number / Patient / Year ** ** 0.97 PLACEBO SALM 50 FP 500 SALM / FP 50/500 * N = 6,113 3-year study *P<0.001 vs placebo **P=0.003 vs placebo Calverley P, et al. Lancet. 2003;361:

20 Fluticasone Propionate/Salmeterol 250/50 and Moderate to Severe COPD Exacerbations (One-Year Data) Exacerbation Rates (per year) % Reduction 1.53 * 1.06 SAL 50 FSC 250/50 * P < SAL 50: Salmeterol (50 mcg) FSC 250/50: Fluticasone (250 mcg) + salmeterol (50 mcg) Ferguson GT, et al. Respir Med. 2008;102:

21 AECOPD Prevention: Budesonide / formoterol vs Fluticasone / salmeterol Swedish retrospective registry review. 9,893 patients on LABA / ICS 28% flutic / sal 72% on bud / form Bud/form 29% less hospitalizations Larsson K. J Intern Med 2013; 273: 584

22 LABA / ICS And Exacerbations ICS / LABA reduces COPD exacerbations in 9 clinical trials in 9921 subjects Most with FEV1 < 50% predicted and history of prior exacerbation LABA exacerbation rate per patient per year Rate ratio 0.76 Evidence quality low Cochrane Review 2012

23 LABA / ICS And Pneumonia Increased pneumonia with inhaled steroids Odds ratio of pneumonia balance reduction in AECOPD against increase in pneumonia. Cochrane Review 2012

24 Question #7 Do adding inhaled medications reduce COPD exacerbations? LABA + LAMA LABA / ICS + LAMA 1. YES 2. NO 3. NOT SURE

25 Umechlidinium and Vilanterol Reduce AECOPD Celli B. CHEST 2014

26 Percent of Patients With Exacerbations (1-year follow-up) OPTIMAL: Exacerbations N= Tiotropium (n=156) No significant differences among groups 64.8 Tiotropium + Salmeterol (n=148) 60.0 Tiotropium + Salmeterol/ Fluticasone (n=145) Assumes all patients lost to follow-up did not have exacerbations (4 for tiotropium, 2 for tiotropium + salmeterol, 2 for tiotropium + salmeterol/fluticasone) Adapted from Aaron SD, et al. Ann Intern Med. 2007;146:

27 OPTIMAL* Tiotropium vs. ICS/LABA Tiotropium +Sal/FP or Tiotropium + Sal alone did not significantly reduce COPD exacerbations compared to Tiotropium alone Tiotropium + Sal/FP did improve hospitalization rates (0.53, ) *Aaron SD, et al. Ann Intern Med. 2007;146(8).

28 CHEST. 2012;141(1): The Impact of Tiotropium on Mortality and Exacerbations When Added to Inhaled Corticosteroids and Long-Acting β-agonist Therapy in COPD Retrospective cohort study of Scottish National Health Service database 1857 COPD patients received LAMA+ICS+LABA 996 COPD patients received ICS+LABA Mean follow-up 4.7 years Kaplan-Meier curve for hospital admission for respiratory disease. Adjusted hazard ratios calculated using Cox regression. P values calculated with the use of log-rank test.

29 CHEST. 2012;141(1): The Impact of Tiotropium on Mortality and Exacerbations When Added to Inhaled Corticosteroids and Long-Acting β-agonist Therapy in COPD Kaplan-Meier curve for all-cause mortality. Adjusted hazard ratios calculated using Cox regression. P values calculated with the use of log-rank test. ICS = inhaled corticosteroid; LABA = long-acting β-agonist; Tio = tiotropium.

30 Question #8 Do you think the WISDOM trial was worthy of publication in the NEJM (novelty, first of its kind, change practice)? 1. YES 2. NO 3. NOT SURE

31 Question #9 Do you think the WISDOM trial design was adequate to answer the question posed? 1. YES 2. NO 3. NOT SURE

32 WISDOM trial: Withdrawal of Inhaled Steroids During Optimized bronchodilator Management Magnussen H, et al. New Engl J Med; Sept 8, 2014

33 ICS Withdrawal: WISDOM Trial Subjects: 2,485 History of AECOPD in last 12 months FEV1 < 50% post-bronchodilator Age > 40. Pack-years >10. Primary outcome: Time to first AECOPD in 12 months Randomized to Continued triple therapy* or Step-wise ICS withdrawal over weeks * Triple therapy: tiotropium + salmeterol, fluticasone 500 ug twice daily

34 COPD Self-Management Programs Run-in on triple therapy, incl fluticasone 1000 ug/day for six months. Then gradual fluticasone withdrawal

35 Study Design Discussion? Population? Gradual tapering of ICS? One-year study: From start of ICS withdrawal? Differential follow-up periods? Generalizability to the real-world

36 ICS Withdrawal: WISDOM Trial ICS withdrawal did not change time to first COPD exacerbation Magnussen H, et al. New Engl J Med. 2014; 371:

37 ICS Withdrawal: WISDOM Trial Magnussen H, et al. New Engl J Med. 2014; 371:

38 ICS Withdrawal: WISDOM Trial ICS withdrawal reduced FEV1: 38 ml at 18 weeks 43 ml at 52 weeks Magnussen H, et al. New Engl J Med. 2014; 371:

39 Result Discussion? Was the chosen outcome reasonable? Are the results plausible? Gradual tapering of ICS? Generalizability to the real-world

40 Question #10 Will the WISDOM impact your clinical practice? 1. YES 2. NO 3. NOT SURE

41 Question #11 How commonly do you employ other treatments to reduce COPD exacerbations in your patients? 1. Frequently 2. Some of the time 3. Rarely 4. NOT SURE

42 Reduction of COPD Exacerbations Smoking cessation Influenza vaccination Pneumococcal vaccination Long-acting bronchodilators Inhaled steroids PDE4 inhibitor Azithromycin Pulmonary rehabilitation Collaborative self-management Long-term oxygen therapy Lung Volume Reduction Surgery

43 Disease Management Program - Failure Randomized controlled trial of comprehensive management compared to guideline-based care Goal: Reduce hospitalizations Program: 4 individual and 1 group session, action plan, proactive phone calls for case management Fan V. Annals Intern Med 2012; 156: 673

44 Objectives Discuss a recent article on reducing therapy for COPD exacerbations the Wisdom trial Understand the importance of COPD exacerbations Know what therapies reduce COPD exacerbations