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2014 by the author

2. “COPD and new treatment options: the role of primary care’’
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Professor of Primary Care Research
Southampton University, UK
ERS 2014

3. Disclosures
Speaker’s honoraria: Astra Zeneca, Boehringer Inglehiem, Aerocrine, Teva and GSK.
Advisory panels: Aerocrine, Almirall, Astra Zeneca, BI, Chiesi, GSK, MSD, Novartis
Sponsorship: GSK, Astra Zeneca, Mundipharma, Aerocrine, BI
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4. Role of Primary Care in COPD treatment
Primary care has a central and fundamental role in COPD
Most patients present initially to Primary Care for diagnosis and management
Many patients are treated only in primary care
Primary care decides on who needs specialist assessment
Most exacerbations present to primary care
Even those under specialist care need Intergrated Care: Coordination of care, co-morbidities

5. New Treatments for COPD
What new treatment options do we have?
Pharmacotherapy
New drug classes, new versions of existing classes, new combinations
New ways of using medicines- new GOLD strategy and risk stratification
Non-pharmacological treatments:
Smoking cessation, exposures, Pulmonary rehabilitation, vaccination, ventilatory support, surgery
Management of co-morbidities

6. © 2014 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-agonists + anticholinergic in one inhaler
Methylxanthines
Inhaled corticosteroids
Combination long-acting beta2-agonists + corticosteroids in one inhaler
Systemic corticosteroids
Phosphodiesterase-4 inhibitors
© 2014 Global Initiative for Chronic Obstructive Lung Disease

7. © 2014 Global Initiative for Chronic Obstructive Lung Disease
Global Strategy for Diagnosis, Management and Prevention of COPD Therapeutic Options: Phosphodiesterase-4 Inhibitors
In patients with severe and very severe COPD (GOLD 3 and 4) and a history of exacerbations and chronic bronchitis, the phospodiesterase-4 inhibitor, roflumilast, reduces exacerbations treated with oral glucocorticosteroids.
Oral, anti-inflammatory
Always with a long acting bronchodilator
Limited role in Primary Care
© 2014 Global Initiative for Chronic Obstructive Lung Disease

8. New versions of existing treatments classes
LABAs
‘Ultra-long acting’- once daily
? Incremental benefits over twice daily treatment
LAMAs
Now other drugs in class, once and twice daily
ICS-LABA combination
ICS Only licensed as combination therapy
New molecule: FF, ?dose equivalence
LABA-LAMA combinations
‘Dual bronchodilators’

9. New molecules for COPD New versions of old classes
LAMA
Umeclidinium
Glycopyrronium
Aclidinium
LABA
Vilanterol
Indercaterol
Olodaterol
ICS
Fluticasone Fuorate
New versions of old classes
Pharmacological differences
In varying combinations- ICS- LABA, LABA-LAMA

10. How important are these to Primary Care?
Always good to have more than one drug in class
May be incremental benefits from new drugs in class
Long duration of action, once daily dosing
Potency
Combinations simplify regimes, may lead to better adherence
New devices and delivery systems may be easier to use
However- by and large benefits are class effects
New ways of using drug classes may be most important

11. Risk Symptoms (C) (D) (B) (A) ≥ 2 or > 1 leading to hospital
Global Strategy for Diagnosis, Management and Prevention of COPD Risk Stratification in COPD
(GOLD Classification of Airflow Limitation))
Risk
(Exacerbation history)
≥ 2 or
> 1 leading
to hospital
admission
1 (not leading
to hospital
admission)
Symptoms
(C)
(D)
(A)
(B)
CAT < 10 4 3 2 1
CAT > 10
mMRC 0–1
mMRC > 2

12. Therapy at Each Stage of COPD
IV: Very Severe
II: Moderate
III: Severe
I: Mild
FEV1/FVC < 70%
FEV1 < 30% predicted
or FEV1 < 50% predicted plus chronic respiratory failure
FEV1/FVC < 70%
30% < FEV1 < 50% predicted
FEV1/FVC < 70%
50% < FEV1 < 80%
predicted
FEV1/FVC < 70%
FEV1 > 80% predicted
Active reduction of risk factor(s); influenza vaccination
Add short-acting bronchodilator (when needed)
This provides a summary of the recommended treatment at each stage of COPD.
Add regular treatment with one or more long-acting bronchodilators (when needed); Add rehabilitation
Add inhaled glucocorticosteroids if repeated exacerbations
Add long term oxygen if chronic respiratory failure. Consider surgical treatments

13. ICS + LABA or LAMA ICS + LABA and/or LAMA > 2 SAMA prn or SABA prn
Global Strategy for Diagnosis, Management and Prevention of COPD Manage Stable COPD: Pharmacologic Therapy RECOMMENDED FIRST CHOICE C D
GOLD 4
ICS + LABA or
LAMA
ICS + LABA
and/or
LAMA
> 2
GOLD 3
Exacerbations per year A B
GOLD 2
SAMA prn or
SABA prn
LABA or
LAMA 1
GOLD 1
mMRC 0-1
CAT < 10
mMRC > 2
CAT > 10
© 2013 Global Initiative for Chronic Obstructive Lung Disease

14. Assess symptoms first (C) (D) (A) (B) If CAT < 10 or mMRC 0-1:
Global Strategy for Diagnosis, Management and Prevention of COPD Combined Assessment of COPD
Assess symptoms first
(C)
(D)
(A)
(B)
If CAT < 10 or mMRC 0-1:
Less Symptoms/breathlessness (A or C)
If CAT > 10 or mMRC > 2:
More Symptoms/breathlessness (B or D)
CAT < 10
CAT > 10
Symptoms
Breathlessness
mMRC 0–1
mMRC > 2
© 2014 Global Initiative for Chronic Obstructive Lung Disease

15. Assess degree of airflow limitation using spirometry
Global Strategy for Diagnosis, Management and Prevention of COPD Assessment of COPD
Assess symptoms
Assess degree of airflow limitation using spirometry
Assess risk of exacerbations
Assess comorbidities
Use history of exacerbations and spirometry.
Two exacerbations or more within the last year
or an FEV1 < 50 % of predicted value are
indicators of high risk. Hospitalization for a COPD exacerbation associated with increased risk of death.
© 2014 Global Initiative for Chronic Obstructive Lung Disease

16. COPD Assessment Test (CAT) or Clinical COPD Questionnaire (CCQ)
Global Strategy for Diagnosis, Management and Prevention of COPD Assessment of COPD
Assess symptoms
Assess degree of airflow limitation using spirometry
Assess risk of exacerbations
Assess comorbidities
COPD Assessment Test (CAT) or
Clinical COPD Questionnaire (CCQ)
mMRC Breathlessness scale
© 2014 Global Initiative for Chronic Obstructive Lung Disease

17. Interpreting the score: <10: Low impact
10-20: Medium impact, room for improvement
>20: High impact: increase therapy, consider referral

18. © 2014 Global Initiative for Chronic Obstructive Lung Disease
Global Strategy for Diagnosis, Management and Prevention of COPD Modified MRC (mMRC)Questionnaire
© 2014 Global Initiative for Chronic Obstructive Lung Disease

19. © 2014 Global Initiative for Chronic Obstructive Lung Disease
Global Strategy for Diagnosis, Management and Prevention of COPD Assess Risk of Exacerbations
To assess risk of exacerbations use history of exacerbations and spirometry:
Two or more exacerbations within the last year or an FEV1 < 50 % of predicted value are indicators of high risk.
One or more hospitalizations for COPD exacerbation should be considered high risk.
© 2014 Global Initiative for Chronic Obstructive Lung Disease

20. What drugs are we using?

21. ICS use and GOLD recommendations (1)
% Patients
Patients (%)
COPD = chronic obstructive pulmonary disease; GOLD = Global initiative for chronic Obstructive Lung Disease; ICS = inhaled corticosteroid; SABA = short-acting β2 agonist; SAMA = short-acting muscarinic antagonist
In this study, Small et al. performed an analysis of data from the Adelphi Respiratory Disease Specific Programme (a large, multinational, cross-sectional survey, which generates real-world data based on actual clinical practice) to evaluate whether pharmacologic treatment patterns in the real world align with what is recommended for each of the four GOLD patient groups.
The analysis was undertaken between June and September 2011 and collected data from primary and secondary care physicians and their patients (n=1,508) in France, Germany, Italy, Spain, the UK and USA.
Only a small proportion of patients were receiving no treatment and these were confined to GOLD 2011 Group A (3% [1% of the total COPD study population]).
Furthermore, use of relief medication only (SABA/SAMA) was more common in Group A compared with all other groups except Group C; however, the limited number of patients in Group C (n=13) precludes any meaningful interpretation of findings in that patient group.
The high incidence of ICS use observed in this real-world population of COPD patients with Group A or B disease suggests that these patients are not being treated according to GOLD 2011 recommendations, which indicate that this treatment option should be reserved for patients with Group C or D disease.
Reference
Small M, Broomfield S, Higgins V. Quantification and treatment patterns of real-world patients classified by the GOLD 2011 strategy. Eur Respir J 2012;40(Suppl. 56):524s (Abstract P2876).
A (n=152)
B (n=739)
C (n=13)
D (n=604)
Total COPD population (n=2,225)
GOLD group
Patients were assigned to GOLD groups based ion CAT score; COPD = chronic obstructive pulmonary disease; GOLD = Global initiative for chronic Obstructive Lung Disease; ICS = inhaled corticosteroid; LABA = long-acting β2-agonist; LAMA = long-acting muscarinic antagonist; SABA = short-acting β2 agonist; SAMA = short-acting muscarinic antagonist
Small et al.
Eur Respir J 2012 (Abstract P2876)

22. GOLD and primary care Problems with GOLD:
Consistency- categories vary with tool used
Ease of use in Primary Care
Lack of contribution of known risk factors, e.g.smoking
Risk in group B
Comorbidities
Risk stratification is however valid!

25. Asthma and COPD similarities and differences
Postma D et al Clin Chest Med 2014

26. Using drugs better- Dual Bronchodilation
∆=200 mL, p<0.001
∆=80 mL, p<0.001
1.50
∆=90 mL, p<0.001
∆=70 mL, p<0.001
∆=130 mL, p<0.001
1.45
∆=120 mL, p<0.001
∆=130 mL, p<0.001
1.40
Trough FEV1 (L)
1.35
1.30
Trough FEV1 at Week 26 (the primary efficacy endpoint) was significantly improved with QVA149 compared with both indacaterol and glycopyrronium, with significant treatment differences of 70 mL and 90 mL, respectively (both p<0.001). QVA149 also provided significantly higher improvement in trough FEV1 compared with open-label tiotropium and placebo at Week 26, with treatment differences of 80 mL and 200 mL, respectively (p<0.001).
All active treatments were associated with significantly improved trough FEV1 compared with placebo at Week 26 (p<0.001).
Reference
Bateman E et al. Dual bronchodilation with QVA149 versus single bronchodilator therapy: the SHINE study. Eur Respir J Epub ahead of print.
1.25
1.25
1.37
1.36
1.38
1.45
1.20
Placebo
Open-label tiotropium 18 μg q.d.
Glycopyrronium 50 μg q.d.
Indacaterol 150 μg q.d.
QVA /50 μg q.d.
Values are least-squares mean ± standard error
Bateman et al. Eur Respir J 2013 (epub ahead of print)

27. So what’s new in pharmacotherapy
No new classes (PDE4)
Some new ‘within-class’ treatments and delivery systems
Some new single-inhaler combinations (LABA-LAMA)
New concepts : in assessing patients, in using treatments
Better understanding of how to use and target treatments

28. Comorbidities and primary care

29. Psychological co-morbidity and respiratory symptoms
Perception
Behavior
Over-use of rescue bronchodilators
Non-compliance with regular medication
At-risk behaviors (smoking, substance abuse)
Poor self-management
Biological effects- immunology and neurology

30. Understanding your patient- psychological co-morbidity

31. Conclusions
Numerous new products for treating COPD in primary care, but few new classes
Newer versions of exiting treatments may have some incremental benefits:
More potent
Longer lasting
More convenient
LABA-LAMA single-inhaler combinations available
New strategies for directing treatment better

33. GOLD: recommendations for initial pharmacologic treatment
Based on combined assessment of airflow limitation, symptoms and exacerbations
(C)
(D)
GOLD 1
GOLD 2
GOLD 3
GOLD 4
ICS + LABA or LAMA
ICS + LABA and/or LAMA ≥2
or ≥1 leading to hospital admission
ICS+LABA and LAMA or ICS+LABA and PDE4-inh or
LABA and LAMA or
LAMA and PDE4-inh
LABA and LAMA or
LABA and PDE4-inh or
LAMA and PDE4-inh
No. of exacerbations/year
GOLD classification of airflow limitation
SABA or SAMA p.r.n.
 LABA or LAMA
1 (not leading to hospital admission)
LABA or LAMA or
SABA and SAMA
CAT = COPD Assessment Test; GOLD = Global initiative for chronic Obstructive Lung Disease; LABA = long-acting β2-agonist; LAMA = long-acting muscarinic antagonist; mMRC = modified Medical Research Council; PDE4-inh = phosphodiesterase 4 inhibitor; p.r.n. = pro re nata as needed; SABA = short-acting β2-agonist; SAMA = short-acting muscarinic antagonist
Medications in each box are mentioned in alphabetical order and therefore are not necessarily in order of preference.
Alternate choice medications (not shown) can be used alone or in combination with other options in the first or second choices.
Current GOLD guidelines recommend a long-acting bronchodilator (LABA or LAMA) as a first-choice option for patients with COPD in groups B, C or D and as a second choice for patients in group A. For patients in groups B, C and D, a combination of a LABA and LAMA is included as a second-choice option.
Reference
Global initiative for chronic Obstructive Lung Disease (GOLD 2014). Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Updated Last accessed 22 January
LABA and LAMA 
(A)
(B)
CAT ≥10
mMRC ≥2
CAT <10
mMRC 01
(Symptoms)
(Breathlessness)
Recommended first choice
Alternative choice
CAT = COPD Assessment Test; GOLD = Global initiative for chronic Obstructive Lung Disease LABA = long-acting β2-agonist; LAMA = long-acting muscarinic antagonist; mMRC = modified Medical Research Council; PDE4-inh = phosphodiesterase 4 inhibitor; p.r.n. = pro re nata as needed SABA = short-acting β2-agonist; SAMA = short-acting muscarinic antagonist
GOLD 2014