Terry Robinson Respiratory Nurse Consultant

Harrogate and District NHS Foundation Trust

Outline Understand the importance of pharmacotherapy in

COPD management Describe how optimising inhaled therapies can

improve outcomes for patients Recognise the role that nurses have in helping patients

self-manage their condition with the right device

Definition of COPD1,2

COPD, chronic obstructive pulmonary disease; FEV1, forced expired volume in 1 second; FVC, forced vital capacity; 1. NICE clinical guideline 101. Available at: www.nice.org.uk/guidance/cg101 , accessed September 2016; 2. GOLD Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Available at: http://www.goldcopd.org/ (Accessed September 2016).

• COPD is characterised by airflow obstruction that is not fully reversible, does not change markedly over several months and is usually progressive

• COPD is predominantly caused by smoking; other factors (particularly occupational exposures) may also contribute to the development of COPD

• Diagnosis relies on clinical judgement based on: o Personal/medical history (exposure to risk factors such as tobacco smoke or occupational dusts, family

history)

o Physical examination (persistent progressive dyspnoea that worsens with exercise, chronic cough)

o Confirmation of airflow obstruction by spirometry:

Spirometry in COPD: • Airflow obstruction as defined by a post-bronchodilator

FEV1/FVC <70%

Epidemiology1

• About 3 million people have COPD in the UK

• Nearly 900,000 people in England and Wales are diagnosed as having COPD and an estimated 2 million people have COPD which remains undiagnosed

• Symptoms usually develop insidiously making it difficult to determine the true prevalence of the disease

• Most patients are not diagnosed until they are in their fifties

Diagnose COPD: assessment of severity • Assess severity of airflow obstruction using reduction in FEV1

NICE clinical

guideline 12 (2004)

ATS/ERS 2004 GOLD 2008 NICE clinical guideline 101

(2010)

Post-bronchodilator

FEV1/FVC

FEV1 % predicted

Post-bronchodilator

Post-bronchodilator

Post-bronchodilator

< 0.7 80% Mild Stage 1 (mild) Stage 1 (mild)*

< 0.7 50–79% Mild Moderate Stage 2 (moderate)

Stage 2 (moderate)

< 0.7 30–49% Moderate Severe Stage 3 (severe) Stage 3 (severe)

< 0.7 < 30% Severe Very severe Stage 4 (very severe)**

Stage 4 (very severe)**

* Symptoms should be present to diagnose COPD in people with mild airflow obstruction ** Or FEV1 < 50% with respiratory failure

GOLD guidelines: Combined assessment of COPD • Symptoms o Less symptoms: mMRC 0–1 or CAT <10

o More symptoms: mMRC ≥2 or CAT ≥10

• Airflow limitation o Low risk: GOLD I or II

o High risk: GOLD III or IV

• Exacerbations o Low risk: ≤1 per year and no hospitalisation for

exacerbation

o High risk: ≥2 per year or ≥1 with hospitalisation

CAT, COPD assessment test; COPD, chronic obstructive pulmonary disease; GOLD, global initiative for chronic obstructive lung disease; mMRC, modified British Medical Research Council GOLD Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Available at: http://www.goldcopd.org/ (Accessed September 2016).

mMRC 0 – 1; CAT <10 mMRC ≥2; CAT ≥10

B A

D C

Ris

k (G

OLD

cla

ssifi

catio

n of

air

flow

lim

itatio

n)

Risk

(Exacerbation history)

Symptoms (mMRC or CAT score)

*or ≥1 leading to hospital admission **not leading to hospital admission

0

1**

≥2*

I

II

III

IV

Inhaled drugs in COPD The cornerstone of treatment for COPD are

bronchodilators: -short acting β2 agonist (SABA) -short-acting muscarinic antagonist (SAMA) -long-acting β2 agonist (LABA) -long-acting muscarinic antagonist (LAMA) inhaled corticosteroids (ICS)

NICE Recommendations

NICE guidelines: Inhaled therapy for stable COPD

COPD, chronic obstructive pulmonary disease; FEV1, forced expired volume in 1 second; ICS, inhaled corticosteroid; LABA, long acting β2 agonist; LAMA, long acting muscarinic antagonist; SABA, short acting β2 agonist; SAMA, short acting muscarinic antagonist NICE clinical guideline 101. Available at: www.nice.org.uk/guidance/cg101 , accessed September 2016. Reproduced with permission

• NICE suggests the following when choosing a delivery system (e.g. inhalers, spacers or nebulisers) and an inhaled therapy: o Choose a drug based on the person’s symptomatic response and preference, the drug’s side effects, potential to reduce

exacerbations and cost o Be aware of the potential risk of developing side effects (including non-fatal pneumonia) in people with COPD treated

with inhaled corticosteroids and be prepared to discuss this with patients

SABA or SAMA as required (may continue at all stages)

Breathlessness and/or exercise limitation

Exacerbations or persistent breathlessness

Persistent exacerbations or breathlessness

LAMA + LABA/ICS combination inhaler

FEV1 ≥50% FEV1 <50%

Consider Consider Consider

LABA/ICS combination inhaler; consider

LABA/LAMA if ICS declined or not tolerated

LAMA in preference to SAMA 4x/day

(discontinue SAMA)

LABA/ICS combination inhaler; consider

LABA/LAMA if ICS declined or not tolerated

LABA LAMA in preference to

SAMA 4x/day (discontinue SAMA)

GOLD guidelines: Pharmacologic therapy for stable COPD*

*Medications are listed in alphabetical order and not necessarily in order of preference; **Medications in this column can be used alone or in combination with other options in the First and Alternative choice columns

COPD, chronic obstructive pulmonary disease; ICS, inhaled corticosteroid; LABA, long acting β2 agonist; LAMA, long acting muscarinic antagonist; PDE4, phosphodiesterase-4; SABA, short acting β2 agonist; SAMA, short acting muscarinic antagonist The Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2016. Available from: http://www.goldcopd.org/ (Accessed September 2016).

Patient group Recommended first choice Alternative choice Other possible treatments**

A SAMA when necessary

or SABA when necessary

LAMA or

LABA or

SABA and SAMA

Theophylline

B LAMA

or LABA

LABA and LAMA

SABA and/or SAMA

Theophylline

C ICS + LABA

or LAMA

LABA and LAMA or

LAMA and PDE4 inhibitor or

LABA and PDE4 inhibitor

SABA and/or SAMA

Theophylline

D ICS + LABA

and/or LAMA

ICS + LABA and LAMA or

ICS + LABA and PDE4 inhibitor or

LAMA and LABA or

LAMA and PDE4 inhibitor

Carbocysteine

N-acetylcysteine

SABA and/or SAMA

Theophylline

LABA/LAMA combination therapy: GOLD recommendations

*Medications in each box are mentioned in alphabetical order, and therefore not necessarily in order of preference; **Medications in this column can be used alone or in combination with other options in the recommended first choice and alternative choice columns ICS, inhaled corticosteroid; LABA, long acting β2 agonist; LAMA, long acting muscarinic antagonist; PDE4, phosphodiesterase-4; SABA, short acting β2 agonist; SAMA, short acting muscarinic antagonist The Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2016. Available from: http://www.goldcopd.org/ (Accessed September 2016).

Patient group Recommended first choice Alternative choice Other possible treatments**

A SAMA when necessary

or SABA when necessary

LAMA or LABA or

SABA and SAMA Theophylline

B LAMA

or LABA

LABA and LAMA

SABA and/or SAMA

Theophylline

C ICS + LABA

or LAMA

LABA and LAMA or LAMA and PDE4 inhibitor or

LABA and PDE4 inhibitor

SABA and/or SAMA

Theophylline

D ICS + LABA

and/or LAMA

ICS + LABA and LAMA or ICS + LABA and PDE4 inhibitor or

LAMA and LABA or LAMA and PDE4 inhibitor

Carbocysteine N-acetylcysteine

SABA and/or SAMA Theophylline

The GOLD guidelines recommend a LABA/LAMA combination therapy as an alternative choice for COPD patients in Group B or C; patients that have a low risk of exacerbations and more symptoms, or those that have a high risk of exacerbations and fewer symptoms

LABA/LAMA combination therapy: Mechanism of action

COPD, chronic obstructive pulmonary disease; LABA, long acting β2 agonist; LAMA, long acting muscarinic antagonist 1. Cazzola M & Page C. Breathe 2014;10:111–120; 2. Singh D. Br J Clin Pharmacol 2015;79:695–708; 3. Spina D. Eur Clin Respir J 2015;2:26634; 4. Montuschi P. Int J COPD 2006;1:409–423

Bronchodilators are central to the treatment of COPD.1 These drugs improve symptoms and quality of life by improving airflow and therefore gas exchange, and by reversing air trapping and dynamic lung hyperinflation.2 There are two classes of long-acting bronchodilators, LABAs and LAMAs:3,4

Noradrenaline β2 agonist β2 receptor

Acetylcholine Muscarinic antagonist Muscarinic receptor

adrenergic cholinergic

LABA LAMA Act by mimicking the sympathetic

(adrenergic) nervous system to promote bronchodilation

Act by preventing bronchoconstriction mediated by the parasympathetic

(cholinergic) nervous system

Adrenoreceptors on smooth muscle to increase bronchodilation

Muscarinic receptors on smooth muscle to reduce acetylcholine-mediated

bronchoconstriction (cholinergic tone)

Opens airways Prevents airways from closing

B2 agonist Muscarinic antagonist

Stimulates Blocks

salmeterol, formoterol, indacaterol, olodaterol

tiotropium, glycopyrronium, aclidinium, umeclidinium

LABA/LAMA combination therapy: Rationale for use

LABA, long acting β2 agonist; LAMA, long acting muscarinic antagonist Singh D. Br J Clin Pharmacol 2015;79:695–708

• LABAs and LAMAs alone have shown linear bronchodilation responses at low concentrations that flatten as the dose increases – patients already receiving a high dose will likely not see any benefit from further increases

• LABA/LAMA combinations may allow greater degree of bronchodilation without dose increase, by combining their distinct and complementary mechanisms of action o Studies of long-acting combinations have shown additive lung function vs monotherapies

• Several LABA/LAMA combination therapies have recently been developed, or are currently in development:

• A major goal for LABA/LAMA combination therapy is to improve lung function and therefore outcomes such as exercise tolerance, dyspnoea and quality of life

LABA LAMA Dosing

Indacaterol Glycopyrronium 110/50 µg once daily

Vilanterol Umeclidinium 62.5/25 µg once daily

Formoterol Aclidinium 400/12 µg twice daily

Olodaterol Tiotropium 5/5 µg once daily

LABA/LAMA combination therapy: Comparison to ICS/LABA

AUC, area under the curve from 0–12 hours; FEV1, forced expiratory volume in 1 second; GOLD, global initiative for chronic obstructive lung disease; ICS, inhaler corticosteroid; L, litres; LABA, long acting β2 agonist; LAMA, long acting muscarinic antagonist; NICE, National institute for Health and Care Excellence 1. NICE clinical guideline 101. Available at: www.nice.org.uk/guidance/cg101 , accessed September 2016; 2. GOLD Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease. Available at: http://www.goldcopd.org/ , accessed September 2016). 3. Vogelmeier CF et al. Lancet Respir Med 2013;1:51–60; 4. Singh D. Br J Clin Pharmacol 2015;79:695–7084; 5. Magnussen H et al. N Engl J Med 2014;371:1285–1294

• ICS/LABA (inhaled corticosteroid combined with long-acting β2 agonist) o Recommended by NICE for patients with FEV1 <50% or those with persistent

exacerbations1

o Recommended by GOLD for Group C and D patients, i.e. those with a high risk of exacerbations2

• ICS/LABA vs LABA/LAMA o ILLUMINATE trial: QVA149 vs salmeterol/fluticasone was associated with increased FEV1

AUC0–12h (treatment difference 0.138 L; p<0.0001) at Week 263

o Further studies are required in order to generate head-to-head data regarding ICS/LABA and LABA/LAMA therapies4

o WISDOM trial: no statistically significant difference in the probability of exacerbations between patients on ICS/LABA/LAMA triple therapy vs ICS withdrawn patients (LABA/LAMA) (hazard ratio 1.06, 95% confidence interval 0.94, 1.19)5

How do patients get the most from their medication?

Easy to use Less frequent dosing regimens Quick results Minimal side effects Only effective if the patient can and does use

their inhaler!

Why do patients struggle to use their inhalers?

1.Push tablet out of blister pack

2.Put tablet (or powder) in mouth 3.Swallow (or chew)

Why do patients struggle to use their inhalers?

1.Remove mouthpiece cover 2.Shake inhaler 3.Hold inhaler upright 4.Breath out 5.Place inhaler in mouth 6.Slowly start to breathe in 7.Depress canister 8.Remove inhaler from mouth 9.Hold breath for a few seconds 10. Repeat as above for second puff 11. Replace mouthpiece cover

Patient perception of inhaler technique and actual inhaler technique3

98%

8%

0%

20%

40%

60%

80%

100%

Patients believed they useinhaler correctly

Patients who actually usedinhaler without error

3. Adapted from: Souza ML, et al. J Bras Pneumol. 2009;35:824-831.

Number of patients in study=60

Impact of repeated inhaler instruction on patient adherence5

5. Adapted from: Takemura M, et al. International Journal of COPD 2011; 6 97–104

73%

42%

Number of patients in study=77

Do healthcare professionals have sufficient knowledge of inhaler techniques in order to educate their patients effectively in their use?

150 Healthcare professionals (74 Primary Care Trust;

76 Acute Trust) were asked to demonstrate how they would self-administer a pMDI placebo inhaler

The Group included hospital doctors, hospital nurses, general practitioners, practice nurses, hospital and community pharmacy staff

Baverstock, M et alThorax 2010

Do healthcare professionals have sufficient knowledge of inhaler techniques in order to educate their patients effectively in their use? Each professional was marked against a standard set

by the manufacturer and Education for Health UK They were also asked to demonstrate the correct

inspiratory flow rate using the In-check dial device

70% 7%

23% Incorrect technique

7 steps and inspiratoryflow check correctCorrect technique 7steps

Train the trainers? Few healthcare professionals have sufficient knowledge of inhaler techniques to educate their patients effectively in their use

Baverstock M, et al. Thorax 2010; Vol 65 Suppl 4. A118

Number of HCPs in study=150

Inhaler evaluated: pMDI placebo Inhaler

Incheck Dial

AIMs machine (Aerosol Inhalation Monitor)

£275!!

Inspiratory effort vs flow rate achieved with different inhalers

Respimat ® is a registered trademark of Boehringer Ingelheim; Breezhaler® is a registered trademark of Novartis; Ellipta® is a registered trademark of GlaxoSmithKline; Genuair® is a registered trademark of Astra Zeneca; Turbohaler® is a registered trademark of AstraZeneca L, litres; kPa, kilopascal Adapted from Ciciliani A, et al. poster (on file)

4

Insp

irat

ory

effo

rt (k

Pa) 5

6

3

2

1

0 0 50 100

Flow rate achieved (L/min)

Turbohaler®

Ellipta® Genuair® Diskus® Breezhaler® Respimat®

Inhaler technique Ensure health professionals such

as practice staff and pharmacists have a good inhaler technique

Regular visual review of patients inhaler technique

Self management plan including medication

Regular follow up and support

New Drugs/Devices in asthma and COPD The UK is experiencing an explosion of new drugs and

inhaler devices being licensed for people with respiratory disease

Over 25 different devices now available to prescribe This increases the complexity of prescribing for people

with asthma or COPD The management of how these new products are

introduced into clinical practice is important because they may vary in type of inhaler device and licensing.

Although generic prescribing is rightly being encouraged in primary care to reduce drug expenditure, this is not appropriate for inhaled drugs

Generic prescribing leaves the brand and inhaler device that may be dispensed open to interpretation by the pharmacist and may result in variability in the type of inhaler device the patient receives

This may have negative effects on patient adherence to the inhaled therapy and on the control of their disease.

Generic prescribing NICE technology appraisal guidance 138 2008 Inhalers should be prescribed by Brand name, not

generically

Spot the difference!

Lets get practical!

Tom 57yr old male Ex smoker (26 yr pack

history) FEV1 84% FEV1/FVC ratio 61%

(post bronchodilator) Works as a carpenter Able to walk his dog for 2

miles at own pace <1 exacerbation/year

MRC dyspnoea score 1 CAT score 4 NICE criteria mild

COPD GOLD criteria A

Tom: 1st line-SABA PRN

Dick 57yr old male Ex smoker (26 yr pack

history) FEV1 64% FEV1/FVC ratio 56%

(post bronchodilator) Works as a carpenter Able to walk his dog for

200 yards at own pace <1 exacerbation/year

MRC dyspnoea score 3 CAT score 14 NICE criteria moderate

COPD GOLD criteria B

Dick: LAMA or LABA OD

Dick: LAMA or LABA BD

Harry 57 yr old male Ex smoker (26 yr pack

history) FEV1 44% FEV1/FVC ratio 56% (post

bronchodilator) Works part time as a

carpenter Able to walk his dog for ½

mile at own pace <1 exacerbation/year

MRC dyspnoea score 2 CAT score 8 NICE criteria severe COPD GOLD classification C

Harry: LABA/LAMA Combination

Bob 57 yr old male Ex smoker (26 yr pack

history) FEV1 28% FEV1/FVC ratio 46% (post

bronchodilator) Unable to work now as a

carpenter Unable to walk his dog,

wife has to do it >2 exacerbations/year

MRC dyspnoea score 4 CAT score 30 NICE criteria very severe

COPD GOLD classification D

Bob: ICS/LABA + LAMA

Bob: ICS/LABA + LAMA

Remember! Medication will only be effective if

patients use their device correctly, inhaler technique should be reviewed regularly.

Always consider patient preference and ensure that the device is suitable to their lifestyle.

Try to prescribe the same type of device for all ‘preventer’ medication.

Remember! Look at the whole patient, not just FEV1! Address symptoms and treat aggressively Most patients do not need an ICS or triple therapy

Any Questions?

Thank you!