Role of LABACS

Provides a simple and effective for
COPD and Asthma Management

GOLD Guideline

GOLD 2017 Report: Chapters

1. Definition and Overview

2. Diagnosis and Initial Assessment

3. Evidence Supporting Prevention
& Maintenance Therapy

4. Management of Stable COPD

5. Management of Exacerbations

6. COPD and Comorbidities

© 2017 Global Initiative for Chronic Obstructive Lung Disease

a common preventable and treatable disease. is characterized by persistent airflow limitation that is usually progressive and associated with an enhanced chronic inflammatory response in the airways and the lung to noxious particles or gases. Global Strategy for Diagnosis. n Exacerbations and comorbidities contribute to the overall severity in individual patients. Management and Prevention of COPD Definition of COPD n COPD. © 2016 Global Initiative for Chronic Obstructive Lung Disease .

Management and Prevention of COPD Diagnosis and Assessment: Key Points  A clinical diagnosis of COPD should be considered in any patient who has dyspnea. the presence of a post-bronchodilator FEV1/FVC < 0. chronic cough or sputum production.  Spirometry is required to make the diagnosis. Global Strategy for Diagnosis. © 2015 Global Initiative for Chronic Obstructive Lung Disease . and a history of exposure to risk factors for the disease.70 confirms the presence of persistent airflow limitation and thus of COPD.

Global Strategy for Diagnosis. Management and Prevention of COPD Diagnosis of COPD EXPOSURE TO RISK SYMPTOMS FACTORS shortness of breath tobacco chronic cough occupation sputum indoor/outdoor pollution è SPIROMETRY: Required to establish diagnosis © 2015 Global Initiative for Chronic Obstructive Lung Disease .

Management and Prevention of COPD Manage Exacerbations : Definition An exacerbation of COPD is: “an acute event characterized by a worsening of the patient’s respiratory symptoms that is beyond normal day- to-day variations and leads to a change in medication. Global Strategy for Diagnosis.” © 2015 Global Initiative for Chronic Obstructive Lung Disease .

Global Strategy for Diagnosis. Management and Prevention of COPD Manage Exacerbations: Key Points  The most common causes of COPD exacerbations are viral upper respiratory tract infections and infection of the tracheobronchial tree.  The goal of treatment is to minimize the impact of the current exacerbation and to prevent the development of subsequent exacerbations. © 2015 Global Initiative for Chronic Obstructive Lung Disease .  Diagnosis relies exclusively on the clinical presentation of the patient complaining of an acute change of symptoms that is beyond normal day-to- day variation.

75 0 1 2 3 4 Years Donaldson et al Thorax.57(10):847-52 . FEV1 decline over 4 years and exacerbation frequency 0. 2002 .85 OF EXACERBATIONS 0.90 Infrequent exacerbators FEV1 (l) 25% of FEV1 DECLINE ATTRIBUTED TO EFFECT 0.80 0.95 Frequent exacerbators 0.

Am J Respir Crit Care Med 1998.157:1418–1422.0005 SGRQ score 60 P = 0. .002 40 20 0 Total Symptoms Activities Impacts SGRQ = St. et al. George’s Respiratory Questionnaire Seemungal TA.001 P < 0. Frequent exacerbations impair health status in COPD Exacerbation frequency Worse 0–2/year 100 3–8/year P =0.0005 80 P < 0.

et al.0001 0.069 0.8 Survival probability P < 0. Thorax 2005.0002 0.2 0 0 10 20 30 40 50 60 Time (months) Soler-Cataluna JJ.60:925–931.0 0 exacerbations 1–2 exacerbations ≥ 3 exacerbations 0.4 P = 0. . Increased frequency of exacerbations increases the risk of mortality in COPD 1.6 P < 0.

prior year (n=1813) 75% COPD Hospitalization. ECLIPSE – Survival curves related to prior hospitalization history 100% 100% 95% 95% Percent Survival 90% 90% 85% 85% 80% 80% No COPD Hospitalization. prior year (n=325) 75% 0 6 12 18 24 30 36 Months Observed Anzueto et al ATS (abstract 5374) 2011 .

one 0 20 40 60 80 100 4% exacerbation. Exacerbation history: powerful predictor of exacerbations 1 exacerbation in year 1 ≥ 1 exacerbation in year 2 Year 1 Year 2 Year 3 23% 6% Exacerbations in the following year 2% 0 20 40 60 80 100 6% 3% Patients with no exacerbation 2% Patients with 1 exacerbation 0 20 40 60 80 100 Patients with ≥2 exacerbations 2% 0 20 40 60 80 100 2% 1% Percent 0 20 40 60 80 100 5% 3% 1% 0 20 40 60 80 100 3% 2% 2% 0 20 40 60 80 100 2% 0 20 40 60 80 100 0 20 40 60 80 100 2% 3% Percent Percent 0 20 40 60 80 100 2% 1% 1% N=1679 patients who 0 20 40 60 80 100 completed the 3-year study 2% 2% 3% The percentages at right denote the proportions of 0 20 40 60 80 100 1% all patients with no exacerbations. or two or more exacerbations Percent 12% Hurst JR et al. N Engl J Med 2010.363:1128-1138 0 20 40 60 80 100 .

ECLIPSE .COPD hospitalizations by GOLD Stage GOLD II GOLD III GOLD IV 60% 50% 40% 30% 20% 10% 0% Year 1 Year 2 Year 3 Overall Anzueto et al ATS (abstract 5374) 2011 .

370:786-796.. and Donaldson GC and Wedzicha JA. Frequent exacerbations drive disease progression PATIENTS WITH FREQUENT EXACERBATIONS Lower quality of life Increased mortality Increased Increased risk of recurrent exacerbations inflammation Faster disease Increased likelihood progression of hospitalisation Adapted from Wedzicha JA and Seemungal TA.61:164-168. Lancet 2007. . Thorax 2006.

One or more hospitalizations for COPD exacerbations should be considered high risk.) Patient Characteristic Spirometric Exacerbations CAT mMRC Classification per year Low Risk A GOLD 1-2 ≤1 < 10 0-1 Less Symptoms Low Risk B GOLD 1-2 ≤1 > 10 >2 More Symptoms High Risk C GOLD 3-4 >2 < 10 0-1 Less Symptoms High Risk >2 D GOLD 3-4 >2 > 10 More Symptoms © 2015 Global Initiative for Chronic Obstructive Lung Disease . choose the highest risk according to GOLD grade or exacerbation history. Global Strategy for Diagnosis. Management and Prevention of COPD Combined Assessment of COPD When assessing risk.

Global Strategy for Diagnosis. Management and Prevention of COPD. 2015: Chapters n Definition and Overview n Diagnosis and Assessment n Therapeutic Options n Manage Stable COPD n Manage Exacerbations n Manage Comorbidities Updated 2015 n Asthma COPD Overlap Syndrome (ACOS) © 2015 Global Initiative for Chronic Obstructive Lung Disease .

nasal spray. Management and Prevention of COPD Therapeutic Options: Smoking Cessation  Counseling delivered by physicians and other health professionals significantly increases quit rates over self- initiated strategies. and nortriptyline reliably increases long- term smoking abstinence rates and are significantly more effective than placebo. bupropion. inhaler. transdermal patch. Even a brief (3-minute) period of counseling to urge a smoker to quit results in smoking quit rates of 5-10%. © 2015 Global Initiative for Chronic Obstructive Lung Disease .  Nicotine replacement therapy (nicotine gum. Global Strategy for Diagnosis. sublingual tablet. or lozenge) as well as pharmacotherapy with varenicline.

Brief Strategies to Help the Patient Willing to Quit Smoking • ASK Systematically identify all tobacco users at every visit • ADVISE Strongly urge all tobacco users to quit • ASSESS Determine willingness to make a quit attempt • ASSIST Aid the patient in quitting • ARRANGE Schedule follow-up contact. © 2015 Global Initiative for Chronic Obstructive Lung Disease .

Global Strategy for Diagnosis. Management and Prevention of COPD Therapeutic Options: COPD Medications Beta2-agonists Short-acting beta2-agonists Long-acting beta2-agonists Anticholinergics Short-acting anticholinergics Long-acting anticholinergics Combination short-acting beta2-agonists + anticholinergic in one inhaler Combination long-acting beta2-agonist + anticholinergic in one inhaler Methylxanthines Inhaled corticosteroids Combination long-acting beta2-agonists + corticosteroids in one inhaler Systemic corticosteroids Phosphodiesterase-4 inhibitors © 2015 Global Initiative for Chronic Obstructive Lung Disease .

Pharmacologic Therapy © 2017 Global Initiative for Chronic Obstructive Lung Disease .

Pharmacologic Therapy © 2017 Global Initiative for Chronic Obstructive Lung Disease .

theophylline or combination therapy.  Bronchodilators are prescribed on an as-needed or on a regular basis to prevent or reduce symptoms. Global Strategy for Diagnosis.  The principal bronchodilator treatments are beta2- agonists. © 2015 Global Initiative for Chronic Obstructive Lung Disease . anticholinergics.  The choice of treatment depends on the availability of medications and each patient’s individual response in terms of symptom relief and side effects.. Management and Prevention of COPD Therapeutic Options: Bronchodilators  Bronchodilator medications are central to the symptomatic management of COPD.

Management and Prevention of COPD Therapeutic Options: Bronchodilators  Long-acting inhaled bronchodilators are convenient and more effective for symptom relief than short-acting bronchodilators.  Long-acting inhaled bronchodilators reduce exacerbations and related hospitalizations and improve symptoms and health status. © 2015 Global Initiative for Chronic Obstructive Lung Disease . Global Strategy for Diagnosis.  Combining bronchodilators of different pharmacological classes may improve efficacy and decrease the risk of side effects compared to increasing the dose of a single bronchodilator.

Management and Prevention of COPD Therapeutic Options: Inhaled Corticosteroids  Regular treatment with inhaled corticosteroids improves symptoms. © 2015 Global Initiative for Chronic Obstructive Lung Disease .  Inhaled corticosteroid therapy is associated with an increased risk of pneumonia.  Withdrawal from treatment with inhaled corticosteroids may lead to exacerbations in some patients. lung function and quality of life and reduces frequency of exacerbations for COPD patients with an FEV1 < 60% predicted. Global Strategy for Diagnosis.

 Combination therapy is associated with an increased risk of pneumonia. Management and Prevention of COPD Therapeutic Options: Combination Therapy  An inhaled corticosteroid combined with a long-acting beta2-agonist is more effective than the individual components in improving lung function and health status and reducing exacerbations in moderate to very severe COPD.  Addition of a long-acting beta2-agonist/inhaled glucorticosteroid combination to an anticholinergic (tiotropium) appears to provide additional benefits. Global Strategy for Diagnosis. © 2015 Global Initiative for Chronic Obstructive Lung Disease .

Global Strategy for Diagnosis. Management and Prevention of COPD Therapeutic Options: Systemic Corticosteroids  Chronic treatment with systemic corticosteroids should be avoided because of an unfavorable benefit-to- risk ratio. © 2015 Global Initiative for Chronic Obstructive Lung Disease .

Global Strategy for Diagnosis.  Low dose theophylline reduces exacerbations but does not improve post-bronchodilator lung function. Management and Prevention of COPD Therapeutic Options: Theophylline  Theophylline is less effective and less well tolerated than inhaled long-acting bronchodilators and is not recommended if those drugs are available and affordable.  There is evidence for a modest bronchodilator effect and some symptomatic benefit compared with placebo in stable COPD. Addition of theophylline to salmeterol produces a greater increase in FEV1 and breathlessness than salmeterol alone. © 2015 Global Initiative for Chronic Obstructive Lung Disease .

The use of antibiotics. © 2015 Global Initiative for Chronic Obstructive Lung Disease . Pneumococcal polysaccharide vaccine is recommended for COPD patients 65 years and older and for COPD patients younger than age 65 with an FEV1 < 40% predicted. other than for treating infectious exacerbations of COPD and other bacterial infections. Global Strategy for Diagnosis. Management and Prevention of COPD Therapeutic Options: Other Pharmacologic Treatments Influenza vaccines can reduce serious illness. is currently not indicated.

overall benefits are very small. The use of endothelium-modulating agents for the treatment of pulmonary hypertension associated with COPD is not recommended. Global Strategy for Diagnosis. Vasodilators: Nitric oxide is contraindicated in stable COPD. Antitussives: Not recommended. © 2015 Global Initiative for Chronic Obstructive Lung Disease . Management and Prevention of COPD Therapeutic Options: Other Pharmacologic Treatments Alpha-1 antitrypsin augmentation therapy: not recommended for patients with COPD that is unrelated to the genetic deficiency. Mucolytics: Patients with viscous sputum may benefit from mucolytics.

the more effective the results. Management and Prevention of COPD Therapeutic Options: Rehabilitation  All COPD patients benefit from exercise training programs with improvements in exercise tolerance and symptoms of dyspnea and fatigue.  If exercise training is maintained at home. the longer the program continues. the patient's health status remains above pre- rehabilitation levels. © 2015 Global Initiative for Chronic Obstructive Lung Disease .  Although an effective pulmonary rehabilitation program is 6 weeks. Global Strategy for Diagnosis.

Ventilatory Support: Combination of noninvasive ventilation (NIV) with long-term oxygen therapy may be of some use in a selected subset of patients. © 2015 Global Initiative for Chronic Obstructive Lung Disease . Global Strategy for Diagnosis. particularly in those with pronounced daytime hypercapnia. resting hypoxemia. Management and Prevention of COPD Therapeutic Options: Other Treatments Oxygen Therapy: The long-term administration of oxygen (> 15 hours per day) to patients with chronic respiratory failure has been shown to increase survival in patients with severe.

© 2015 Global Initiative for Chronic Obstructive Lung Disease . lung transplantation has been shown to improve quality of life and functional capacity. In appropriately selected patients with very severe COPD. Management and Prevention of COPD Therapeutic Options: Surgical Treatments Lung volume reduction surgery (LVRS) is more efficacious than medical therapy among patients with upper-lobe predominant emphysema and low exercise capacity. LVRS is costly relative to health-care programs not including surgery. Global Strategy for Diagnosis.

Global Strategy for Diagnosis, Management and
Prevention of COPD, 2015: Chapters

n Definition and Overview
n Diagnosis and Assessment
n Therapeutic Options
n Manage Stable COPD
n Manage Exacerbations
n Manage Comorbidities
Updated 2015 n Asthma COPD Overlap
Syndrome (ACOS)
© 2015 Global Initiative for Chronic Obstructive Lung Disease

Global Strategy for Diagnosis, Management and Prevention of COPD

Manage Stable COPD: Goals of Therapy

 Relieve symptoms
 Improve exercise tolerance Reduce
symptoms
 Improve health status

 Prevent disease progression
Reduce
 Prevent and treat exacerbations risk
 Reduce mortality
© 2015 Global Initiative for Chronic Obstructive Lung Disease

Global Strategy for Diagnosis, Management and Prevention of COPD
Manage Stable COPD: All COPD Patients

 Avoidance of risk factors
- smoking cessation
- reduction of indoor pollution
- reduction of occupational exposure
 Influenza vaccination
© 2015 Global Initiative for Chronic Obstructive Lung Disease

C. D Physical activity Pneumococcal treatment) vaccination Pulmonary rehabilitation © 2015 Global Initiative for Chronic Obstructive Lung Disease . Global Strategy for Diagnosis. Management and Prevention of COPD Manage Stable COPD: Non-pharmacologic Patient Essential Recommended Depending on local Group guidelines Smoking cessation (can Flu vaccination A include pharmacologic Physical activity Pneumococcal treatment) vaccination Smoking cessation (can Flu vaccination include pharmacologic B.

Management and Prevention of COPD Manage Stable COPD: Pharmacologic Therapy RECOMMENDED FIRST CHOICE C D Exacerbations per year GOLD 4 ICS + LABA ICS + LABA 2 or more or and/or or LAMA LAMA > 1 leading GOLD 3 to hospital admission A B GOLD 2 1 (not leading SAMA prn LABA to hospital or or admission) GOLD 1 SABA prn LAMA 0 CAT < 10 CAT > 10 mMRC 0-1 mMRC > 2 © 2015 Global Initiative for Chronic Obstructive Lung Disease . Global Strategy for Diagnosis.

Management and Prevention of COPD Manage Stable COPD: Pharmacologic Therapy ALTERNATIVE CHOICE C D LAMA and LABA ICS + LABA and LAMA Exacerbations per year GOLD 4 or or 2 or more ICS + LABA and PDE4-inh LAMA and PDE4-inh or or or LAMA and LABA > 1 leading GOLD 3 LABA and PDE4-inh or to hospital LAMA and PDE4-inh. Global Strategy for Diagnosis. admission A B GOLD 2 LAMA 1 (not leading or LAMA and LABA to hospital LABA admission) GOLD 1 or SABA and SAMA 0 CAT < 10 CAT > 10 mMRC 0-1 mMRC > 2 © 2014 Global Initiative for Chronic Obstructive Lung Disease .

Global Strategy for Diagnosis. Management and Prevention of COPD Manage Stable COPD: Pharmacologic Therapy OTHER POSSIBLE TREATMENTS C D SABA and/or SAMA Carbocysteine Exacerbations per year GOLD 4 2 or more N-acetylcysteine or Theophylline SABA and/or SAMA > 1 leading GOLD 3 to hospital Theophylline admission A B GOLD 2 1 (not leading SABA and/or SAMA to hospital Theophylline admission) GOLD 1 Theophylline 0 CAT < 10 CAT > 10 mMRC 0-1 mMRC > 2 © 2015 Global Initiative for Chronic Obstructive Lung Disease .

WHICH COPD PATIENTS BENEFIT FROM ICS TREATMENT? .

The Eosinophil Story .

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LABA alone SYMBICORT 104 Formoterol 102 Budesonide 100 Mean FEV1 (% of baseline) Placebo 98 96 94 92 90 88 86 84 82 80 –0. formoterol. Eur Respir J 2003. P < 0. et al. P = 0. placebo and budesonide. Bud/Form: Efficacy in COPD Treatment produces maintained improvement in lung function vs. placebo Calverley PM.22:912–919.001 SYMBICORTvs.002 SYMBICORTvs.001 formoterol vs. .5 0 1 2 3 4 5 6 7 8 9 10 11 12 Time from randomisation (months) P < 0.

005 P= 0. et al.17 P=0. .30 -0.012 –0.047 –0.12 P= 0.Bud/Form significantly improves symptoms within 1 week vs.25 -0.20 -0.20 -0.35 Mean change in symptom score vs.05 0 Night-time Shortness Cough Chest awakening of breath tightness  Patients had more rapid symptom relief with Symbicort due to the addition of ICS Szafranski W.15 –0.21:74–81. SYMBICORT placebo after 1 week of treatment –0. Eur Respir J 2003.10 –0.13 Formoterol P=0. LABA alone –0.038 –0.

formoterol Calverley PM. P = 0. placebo.05 vs. et al.015 Symbicort vs. . Bud/Form reduces the rate of exacerbations requiring medical intervention vs. * formoterol –30 Symbicort Budesonide Formoterol  Treating 100 patients with COPD (GOLD stage III–IV) with Symbicort instead of formoterol alone may prevent 47 exacerbations in 1 year *P < 0. Eur Respir J 2003.1 –10 2 –12% –15 1 –20 –25 –24% 0 Symbicort vs.22:912–919. LABA alone 5 +3% Rate of exacerbations/patient/year 0 3 Number needed to treat –5 2.

p<0.0 62% 0 15 30 45 60 75 90 Days since randomisation CLIMB study Cox-proportional hazards: rate ratio 0. 0.2 0. Am J Respir Crit Care Med 2009.25. 180: 741–750. Official Journal of the American Thoracic Society.3 0.Bud/Form as a combine therapy Rate of severe exacerbations reduced by 62% with budesonide/formoterol plus tiotropium compared with tiotropium alone Budesonide/formoterol + tiotropium 0.001) Figure reproduced from Welte T et al.57.38 (95% CI 0. .1 0. © American Thoracic Society.4 Placebo + tiotropium Exacerbations/patient 0.

001 0.001 p<0.001 0.150 0.001 0.130 Breathlessness Chest Cough Night-time tightness awakenings CLIMB study p values. 180: 741–750. .140 0.145 p<0.155 0.135 0. comparison between budesonide/formoterol plus tiotropium versus placebo plus tiotropium Welte T et al.160 p<0.165 Mean difference in symptom score p<0. Am J Respir Crit Care Med 2009.Budesonide/formoterol plus tiotropium reduced COPD symptom scores compared with tiotropium alone 0.

001 vs.22:912–919. Eur Respir 22: 912-919 J 2003. LABA alone –42% –45 * *P < 0. placebo. P = 0. Calverley EuretRespir J 2003. . PM. budesonide.007 SYMBICORT vs. formoterol Calverley PM.009 SYMBICORT vs.5% –25 reduction in rate of –30 oral steroid use –35 –40 vs.5% –14% –20 –30. placebo (%) –10 –15 –13% 30. P = 0. al. et al. Bud/Form reduces the need for oral steroids Symbicort Budesonide Formoterol 0 –5 Hazard ratio for time to first oral steroid course vs.

Bud/Form improves health status within 4 weeks –9 –8 SYMBICORT-treated patients –7 ∆ Health status –6 –5 Clinically –4 meaningful improvement –3 –2 –1 0 Symptoms Activity Impact Total  Symbicort leads to clinically relevant improvements in SGRQ scores vs baseline within just 4 weeks of treatment in patients with moderate-to-severe COPD SGRQ = St George’s Respiratory Questionnaire Bourbeau J. .26(Suppl 49):296s. et al. Eur Respir J 2005.

LABA. Confidential slide set . short-acting β2 agonists Yearly rate of events calculated using Poisson regression AZ data on file These data are communicated for scientific purpose only. Prescriptions of COPD related medications ICS. inhaled corticosteroids. SABA. long-acting β2 agonists.

fluticasone/salmeterol AZ data on file These data are communicated for scientific purpose only. FLU/SAL.0001. Confidential slide set . CI. BUD/FORM.4 NNT = 16 Adjusted yearly rates of healthcare utilisation events were compared using Poisson regression analysis. confidence intervals. budesonide/formoterol. **P<0. *P=0. COPD Exacerbations Events per 100 patient/years for exacerbations in propensity matched COPD patients treated with BUD/FORM (n=2734) or FLU/SAL (n=2734) NNT = 3.0003 for difference.

001 for all. confidence intervals. fluticasone/salmeterol AZ data on file These data are communicated for scientific purpose only. Pneumonia-related events Pneumonia events in propensity matched COPD patients BUD/FORM (n=2734) or FLU/SAL (n=2734) Adjusted yearly pneumonia event rates compared using Poisson regression analysis. budesonide/formoterol. BUD/FORM. FLU/SAL. P<0. Confidential slide set . CI.

GINA 2016 Updated These data are communicated for scientific purpose only. Confidential slide set .

Confidential slide set .These data are communicated for scientific purpose only.

the CONTROLLER treatment preferred Step 3 treatment is CHOICE e. #For patients prescribed Low dose mepolizumab* Low dose ICS BDP/formoterol or BUD/ ICS/LABA** formoterol maintenance and reliever therapy Other Consider low Leukotriene receptor antagonists (LTRA) Med/high dose ICS Add tiotropium* Add low controller dose ICS Low dose theophylline* Low dose ICS+LTRA High dose ICS dose OCS  Tiotropium by mist inhaler is + LTRA options (or + theoph*) (or + theoph*) an add-on treatment for patients ≥12 years with a As-needed short-acting beta2-agonist (SABA) As-needed SABA or history of exacerbations RELIEVER low dose ICS/formoterol# GINA 2016.pharmacotherapy UPDATED! Diagnosis Symptom control & risk factors (including lung function) Inhaler technique & adherence Patient preference Symptoms Exacerbations Side-effects Asthma medications Patient satisfaction Non-pharmacological strategies Lung function Treat modifiable risk factors STEP 5 STEP 4 STEP 3 Refer for *Not for children <12 years PREFERRED STEP 1 STEP 2 add-on **For children 6-11 years. Med/high tiotropium.* medium dose ICS ICS/LABA omalizumab. Stepwise management . Box 3-5 (2/8) (upper part) These data are communicated for scientific purpose only. Confidential slide set .g.

the preferred Step 3 treatment is medium dose ICS #For patients prescribed BDP/formoterol or BUD/ formoterol maintenance and reliever therapy  Tiotropium by mist inhaler is an add-on treatment for patients ≥12 years with a history of exacerbations GINA 2016. Box 3-5. Med/high tiotropium. Step 1 – as-needed inhaled short-acting beta2-agonist (SABA) STEP 5 STEP 4 STEP 3 Refer for PREFERRED STEP 1 STEP 2 add-on CONTROLLER treatment CHOICE e.* omalizumab. Step 1 (4/8) These data are communicated for scientific purpose only. Confidential slide set . ICS/LABA mepolizumab* Low dose Low dose ICS ICS/LABA** Other Add tiotropium* Add low Consider low Leukotriene receptor antagonists (LTRA) Med/high dose ICS controller High dose ICS dose OCS dose ICS Low dose theophylline* Low dose ICS+LTRA options + LTRA (or + theoph*) (or + theoph*) As-needed short-acting beta2-agonist (SABA) As-needed SABA or RELIEVER low dose ICS/formoterol# *Not for children <12 years **For children 6-11 years.g.

Step 2 – low-dose controller + as-needed inhaled SABA STEP 5 STEP 4 STEP 3 Refer for STEP 1 STEP 2 add-on treatment e. the preferred Step 3 treatment is medium dose ICS #For patients prescribed BDP/formoterol or BUD/ formoterol maintenance and reliever therapy  Tiotropium by mist inhaler is an add-on treatment for patients ≥12 years with a history of exacerbations GINA 2016. Box 3-5. Confidential slide set . Med/high tiotropium.* omalizumab. Step 2 (5/8) These data are communicated for scientific purpose only. ICS/LABA mepolizumab* Low dose Low dose ICS ICS/LABA** Other Consider low Med/high dose ICS Add tiotropium* Add low Leukotriene receptor antagonists (LTRA) controller dose ICS Low dose ICS+LTRA High dose ICS dose OCS Low dose theophylline* options (or + theoph*) + LTRA (or + theoph*) RELIEVER As-needed short-acting beta2-agonist (SABA) As-needed SABA or low dose ICS/formoterol# *Not for children <12 years **For children 6-11 years.g.

ICS/LABA mepolizumab* Low dose Low dose ICS ICS/LABA** Other Consider low Leukotriene receptor antagonists (LTRA) Med/high dose ICS Add tiotropium* Add low controller Low dose ICS+LTRA High dose ICS dose OCS dose ICS Low dose theophylline* options (or + theoph*) + LTRA (or + theoph*) As-needed short-acting beta2-agonist (SABA) As-needed SABA or low dose ICS/formoterol# RELIEVER *Not for children <12 years **For children 6-11 years. CONTROLLER Med/high tiotropium. Step 3 (6/8) These data are communicated for scientific purpose only. Step 3 – one or two controllers + as-needed inhaled reliever STEP 5 STEP 4 STEP 3 Refer for STEP 1 STEP 2 add-on treatment PREFERRED e.Initiative © Global Confidential slide set for Asthma .g. Box 3-5.* CHOICE omalizumab. the preferred Step 3 treatment is medium dose ICS #For patients prescribed BDP/formoterol or BUD/ formoterol maintenance and reliever therapy  Tiotropium by mist inhaler is an add-on treatment for patients ≥12 years with a history of exacerbations GINA 2016.

and well tolerated  Acceptance of inhaled steroid  Only one inhaler:  simplified therapy  user friendly  patients’ adherence Acceptance of long-term treatment . effective. Fixed combinations of inhaled steroids plus long-acting ß2-agonists  Logical.

Chest 2006. Bud / Form SMART: 6 double-blind studies in > 14 000 patients STEAM1† 6 months: Bud / Form SMART vs. 2x budesonide Proof of concept + SABA. 368:744–753 5. n = 697 STEP2 12 months: Bud / Form SMART vs. formoterol or SABA. 4 x ICS or Bud / Form + SABA. Respir Med 2007. 101:2437–2446 . Curr Med Res Opin 2004. time to first severe 4. 20:1403–1418 †STEAM not included in pooled analysis as primary 3. n = 2309 2001 2002 2003 2004 2005 2006 2007 Years of clinical trial 1. Int J Clin Pract 2007. Lancet 2006. Kuna et al. Bousquet et al. Rabe et al. 171:129–136 endpoint was morning PEF. Am J Respir Crit Care Med 2005. Scicchitano et al. n = 3394 COMPASS5 Superior to higher 6 months: Bud / Form SMART vs. Salm / FP + SABA. 61:725–73. Bud / Form or fixed-dose Salm / FP + SABA. Rabe et al. n = 2760 Value of reliever SMILE4 component 12 months: Bud / Form + Bud / Form. n = 3335 ICS/LABA AHEAD6 6 months: Bud / Form SMART vs. 129:246–256 2. O’Byrne et al. n = 1890 STAY3 12 months: Bud / Form SMART vs. 2x budesonide Bud / Form SMART clinical trial + SABA. exacerbation was primary endpoint in other 5 studies 6.

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Severe exacerbations requiring intervention in 6 double-blind studies (n = 14 351) BUD + SABA Salm-FP + SABA Exacerbations Bud-Form + SABA Bud-Form SMART [/100 patients/yr] Bud-Form + formoterol *ICS dose of comparator 250* (BDP equivalents) 40 1000* 500* 500* 1000* 1000* 1000* 2000* 500* 30 20 10 0 STEAM STEP AHEAD STAY COMPASS SMILE .

Scicchitano R. 4. Scicchitano et al. et al. Patients treated with SMART use no reliever on most days 1. OVERALL ASTHMA CONTROL: Achieving Current Clinical Control 100 Budesonide + SABA Budesonide/Formoterol + SABA 90 Salmeterol/Fluticasone + SABA Percent of days with reliever use Budesonide/Formoterol SMART 80 70 60 50% of days 50 40 Budesonide 400 µg/d Fluticasone 1000 µg/d Budesonide 800 µg/d Budesonide 800 µg/d Budesonide 640 µg/d Budesonide 160 µg/d Fluticasone 500 µg/d 30 BUD 792 µg/d BUD 483 µg/d 20 10 0 Rabe et al. 3. Bousquet J. et al. Kuna et al. O’Byrne et al. 5. et al. Kuna P. 2. O’Byrne PM. Respir Med 2007 . Chest 2006. Bousquet et al. Int J Clin Pract 2007. et al. Curr Med Res Opin 2004. Am J Respir Crit Care Med 2005. Rabe KF. et al.

001 vs all controls. OVERALL ASTHMA CONTROL: Reducing Future Risk 45 Bud/Form using the SMART approach ≥2 x BUD + SABA Bud/Form + SABA Fluticasone/salmeterol 40 Bud/Form + SABAl + SABA Exacerbations/100 patients/year 35 30 *** * 25 ** 20 *** ** 15 10 *** 5 0 Rabe et al. 3. 2.6+ *p<0. ***p<0.3 Rabe et al. Lancet 2006. Am J Respir Crit Care Med 2005. 4. Chest 2006.05 vs all controls. **p<0. Respir Med 2007 . 5. Curr Med Res Opin 2004. Int J Clin Pract 2007.5+ Bousquet et al. Rabe et al. O’Byrne et al. +Filipino patients participated in the trial SMART reduces the rate of severe exacerbations as reported in numerous clinical trials (Filipino patients included) 1.01 vs all controls.4+ Kuna et al. 6. Scicchitano et al.1+ Scicchitano et al. Kuna et al. Rabe et al.2 O' Byrne et al. Bousquet et al.

GINA 2009 guidelines 2. ICS*plus long glucocorticosteroid agonist acting ß2 -agonist (lowest dose) leukotriene medium.release theophylline CONTROLLER modifier low dose ICS plus sustained release theophylline * inhaled corticosteroid ** receptor antagonist or synthesis inhibitors 1. REDUCE INCREASE TREATMENT STEPS STEP STEP STEP STEP STEP 1 2 3 4 5 asthma education Budesonide / Formoterol (SMART) environmental RELIEVERcontrol as needed rapid-acting as needed rapid acting ß -agonist ß2 -agonist ADD ONE OR ADD ONE OR SELECT ONE SELECT ONE MORE BOTH CONTROLLER OPTIONS low dose ICS*plus medium dose oral low dose ICS* long acting ß2 .or leukotriene anti-IgE modifier** high dose ICS modifier treatment Budesonide /low Formoterol dose ICS plus leukotriene (SMART) sustained . PCCP PCRADM 2009 .

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• Inhaled corticosteroids have a role in some COPD patients • In Asthma. CONCLUSIONS • Inhaled corticosteroids affect lung function. SMART regimen has showed a significant result Vs other ICS/LABA . exacerbation rate and health status in COPD • Other treatments work as well on average as LABA-ICS combinations but may benefit different patients • Eosinophils predict acute exacerbation response to steroids and may identify those with the greatest reductions in exacerbations on ICS.

THANK YOU .