UPDATES IN ASTHMA

AND COPD Audrey Umbreit, PharmD, BCACP

MAPA Pharmacology Conference

May 11, 2018

Objectives

• Review GINA and GOLD guidelines

• Identify patients who would benefit from the following medications: • anti-IgE

• anti-IL5

• Roflumilast

• Chronic macrolide therapy

• Compare / Contrast new inhaler devices • Ellipta

• Respiclick

• Respimat

• Apply the outcomes of new studies to patient case examples

Abbreviations

Medications

• LABA = long acting beta agonist

• LAMA = long acting anti-muscarinic agent

• LTRA = leukotriene receptor antagonist

• ICS = inhaled corticosteroid

• OCS = oral corticosteroid

• PDE4I = phosphodiesterase-4 inhibitor

• SABA = short acting beta agonist

• SAMA = short acting anti-muscarinic agent

Other Abbreviations

• GINA = Global Initiative

for Asthma

• GOLD = Global initiative

for chronic Obstructive

Lung Disease

• PRN = as needed

Drug Classes – Inhaled LABA LAMA LABA/

LAMA

ICS ICS/

LABA

ICS/

LAMA/

LABA

SABA SAMA SAMA/

SABA

Brovana neb

(arformoterol)

Incruse Ellipta

(umeclidinium)

Anoro Ellipta

(umeclidinium/

vilanterol)

ArmonAir

Respiclick

(fluticasone)

Advair HFA

and Diskus

(fluticasone /

salmeterol)

Trelegy Ellipta

(fluticasone/

umeclidinium/

vilanterol)

ProAir HFA

and RespiClick

(albuterol)

Atrovent HFA

(ipratropium)

Combivent

Respimat

(ipratropium/

albuterol)

Perforomist

neb

(formoterol)

Lonhala

Magnair neb (glycopyrrolate)

Bevespi

Aerosphere

(glycopyrrolate

/ formoterol)

Arnuity Ellipta

(fluticasone)

AirDuo

Respiclic

(fluticasone /

salmterol)

Proventil HFA

(albuterol)

Ipratropium

neb (generic)

DuoNeb

(ipratropium/

albuterol

Serevent

Diskus

(salmeterol)

Seebri

Neohaler (glycopyrrolate)

Stiolto

Respimat

(tiotropium/

olodaterol

Asmanex

(mometasone)

Breo Ellipta

(fluticasone /

vilanterol)

Ventolin HFA

(albuterol)

Striverdi

Respimat

(olodaterol)

Spiriva

HandiHaler

and Respimat

(tiotropium)

Utibron

Neohaler

(indacaterol /

glycopyrrolate)

Flovent HFA

and Diskus

(fluticasone)

Dulera

(mometasone /

formoterol)

Xopenex HFA

and neb

(levalbuterol)

Tudorza

Pressair

(aclidinium)

Pulmicort

Flexhaler and

neb

(budesonide)

Symbicort

(budesonide /

formoterol)

Albuterol neb

(generic)

QVAR

RediHaler

(beclo-

methasone)

ASTHMA

2018 GINA Guidelines for Asthma

Step 1

Consider low dose ICS

Step 2 Low dose ICS

LTRA or low dose theophylline

Step 3 Low dose ICS / LABA

Medium/high dose ICS, or Low dose ICS + LTRA

Step 4 Medium-high dose ICS / LABA

Add tiotropium, or high dose ICS + LTRA

Step 5 Refer for add-on treatment e.g. tiotropium, anti-IgE, anti-IL-5

Add low dose OCS

GINA. Pocket guide for asthma management and prevention. Updated 2018.

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Reliever = PRN SABA

• Step 1 • It is explained that the reason ICS should be considered for

patients with mild asthma (rather than prescribing SABA alone) is to reduce their risk of serious exacerbations (Pauwels, Lancet 2003;

O’Byrne AJRCCM 2001; Reddel Lancet 2017)

• Steps 3-4 • From the large FDA LABA safety studies: adding LABA to ICS in a

combination inhaler reduces risk of exacerbations and improves symptoms and lung function, compared with the same dose of ICS alone, but with only a small reduction in reliever use (Stempel NEJM 2016, Peters NEJM 2016)

• Step 5 and Box 3-14: management of severe asthma • Subcutaneous benralizumab (monoclonal anti-IL5 receptor α

antibody) is another add-on treatment for patients aged ≥12 years with severe eosinophilic asthma

Treatment steps – changes in 2018

What’s new in GINA 2018? Slide from www.ginasthma.org

• Perimenstrual (catamenial) asthma – new section added

• Asthma worse premenstrually in ~20% women

• More common in older women, higher BMI, longer duration and

more severe asthma; often have dysmenorrhea, shorter cycles,

longer bleeding; aspirin-exacerbated respiratory disease more

common (Sanchez-Ramos Exp Rev Respir Med 2017)

• Add-on treatment: oral contraceptives and/or LTRA may be helpful

• The recommendation against stopping ICS during

pregnancy has been reinforced

• ICS reduce the risk of exacerbations in pregnancy (Evidence A) (Schatz AAAI 2005; Murphy Clin Chest Med 2011)

• Stopping ICS increases the risk of exacerbations in pregnancy

(Evidence A) (Murphy Thorax 2006)

Perimenstrual asthma, and asthma in

pregnancy

What’s new in GINA 2018? Slide from www.ginasthma.org

Biologic Medications for Asthma:

Mechanism of Action Anti-IL5 (benralizumab,

mepolizumab, reslizumab)

Anti-IgE (omalizumab)

Image from www.pharmacodia.com Image from severeasthma-birmingham.co.uk

Test your skills #1

Which of the following patients would be a candidate for

mepolizumab (anti-IL5)?

A) 6 y/o with severe asthma, ACT = 19, eosinophil count of

150cells/µL, currently taking high-dose ICS

B) 25 y/o with severe asthma, ACT = 16, eosinophil count

of 300cells/µL, currently taking high-dose ICS + LABA

C) 32 y/o with severe asthma, ACT = 15, eosinophil count

of 100cells/µL, currently taking high-dose ICS + LABA

Biologic Medications for Asthma:

Indication and Administration Anti-IL5 (benralizumab,

mepolizumab, reslizumab)

• Indication = Add-on

treatment for adults with

severe asthma with an

eosinophilic phenotype

• Administration = IV or SQ

every 4 to 8 weeks

Anti-IgE (omalizumab)

• Indication = Moderate to

severe persistent asthma

in adults and patients 6

years and older who have

a positive skin test to

perennial aeroallergen

and are inadequately

controlled with ICS

• Administration = SQ

injection every 2-4 weeks

Test your skills #1

Which of the following patients would be a candidate for

mepolizumab (anti-IL5)?

A) 6 y/o with severe asthma, ACT = 19, eosinophil count of

150cells/µL, currently taking high-dose ICS

B) 25 y/o with severe asthma, ACT = 16, eosinophil

count of 300cells/µL, currently taking high-dose ICS

+ LABA

C) 32 y/o with severe asthma, ACT = 15, eosinophil count

of 100cells/µL, currently taking high-dose ICS + LABA

Biologic Medications for Asthma:

Adverse Effects and Cost Anti-IL5 (benralizumab,

mepolizumab, reslizumab)

• ADEs: Headache, injection site reaction, backache, fatigue, pharyngitis

• Cost: • Benralizumab =

$2333/month

• Mepolizumab = $2708/month

• Reslizumab = $1670-2505/month, depending on dose

Anti-IgE (omalizumab)

• ADEs: Injection site

reaction, abdominal pain,

arthralgia, headache,

otitis media,

nasopharyngitis,fever

• Cost = $541-2706/month,

depending on dosage

COPD

COPD Assessment

GOLD. Pocket guide to COPD diagnosis, management, and prevention. 2018.

Test your skills #2

What therapy would be the best choice to add for a 66y/o

COPD patient in Group D, current FEV1<50% predicted,

already taking LAMA/LABA +ICS and has chronic

bronchitis with recurrent exacerbations?

A) Roflumilast

B) Low-dose oral steroid

C) Theophylline

D) Macrolide antibiotic

GOLD Guidelines for COPD

Group C

Group A

Group D

Group B

GOLD. Pocket guide to COPD diagnosis, management, and prevention. 2018.

Test your skills #2

What therapy would be the best choice to add for a 66y/o

COPD patient in Group D, current FEV1<50% predicted,

already taking LAMA/LABA +ICS and has chronic

bronchitis with recurrent exacerbations?

A) Roflumilast

B) Low-dose oral steroid

C) Theophylline

D) Macrolide antibiotic

Roflumilast

• Dose = 500mcg orally once a day

• Mechanism of action: PDE4 inhibitor – leads to increased

cAMP in lung cells, reduced neutrophil and eosinophil

count in the lungs

• Contraindicated in moderate-severe liver impairment

• Adverse effects

• Decreased weight

• Diarrhea, nausea

• Backache, headache

• Cost = $375 per month

New inhaler devices

• Ellipta

• Respiclick

• Respimat

Ellipta

• Anoro = LAMA/LABA

(umeclidinium/vilanterol)

• Arnuity = ICS (fluticasone)

• Breo = ICS/LABA

(fluticasone/vilanterol)

• Incruse = LAMA

(umeclidinium)

• Trelegy = ICS/LAMA/LABA

(fluticasone / umeclidinium

/ vilanterol)

Ellipta: How to Use

• All doses are 1 inhalation once a day

Respiclick

• Armonair = ICS

(fluticasone)

• ProAir = SABA (albuterol)

• AirDuo = ICS/LABA

(fluticasone/salmeterol)

Respiclick: How to use

Step 1: Holding the inhaler upright,

open the cap until it clicks Step 2: Exhale completely Step 3: Put mouthpiece in mouth

and close lips tightly. Breath in

quickly and deeply through the

mouth

Make sure fingers or lips do not

block the vent

Close the cap after each

inhalation

The dose counter will display

how many inhalations remain

Respimat

• Combivent = SAMA/SABA

(ipratropium/albuterol)

• Spiriva = LAMA

(tiotropium)

• Stiolto = LAMA/LABA

(tiotropium/olodaterol)

• Striverdi = LABA

(olodaterol)

Respimat: How to use

Step 1: Turn the canister in the

direction of the arrows until it

clicks (1/2 turn)

Step 2: Open the cap Step 3: Close lips around

mouthpiece without covering

air vents. Press the dose-

release button while taking a

slow, deep breath through

mouth

Note that when first used, canister must be inserted

into the respimat device and primed according to

specific product instructions

Importance of Verifying Inhaler Technique

NEW CLINICAL TRIALS

Clinical Trials

• AMAZES: Effect of azithromycin on asthma exacerbations

• IMPACT: Effect of once-daily LABA/LAMA/ICS combo vs

LAMA/LABA and LABA/ICS

AMAZES

• N=420 adults with symptomatic asthma despite ICS/LABA

• Exclusion: Polonged QTc, hearing impairment

• Azithromycin 500mg three times per week vs. Placebo

• Duration – 48 weeks

• Primary endpoint: rate of asthma exacerbations

The Lancet 2017 390, 659-668DOI: (10.1016/S0140-6736(17)31281-3)

Results

The Lancet 2017 390, 659-668DOI: (10.1016/S0140-6736(17)31281-3)

NNT = 6

Step 1

Consider low dose ICS

Step 2 Low dose ICS

LTRA or low dose theophylline

Step 3 Low dose ICS / LABA

Medium/high dose ICS, or Low dose ICS + LTRA

Step 4 Medium-high dose ICS / LABA

Add tiotropium, or high dose ICS + LTRA

Step 5 Refer for add-on treatment e.g. tiotropium, anti-IgE, anti-IL-5

Add low dose OCS

2018 GINA Guidelines for Asthma

GINA. Pocket guide for asthma management and prevention. Updated 2018.

Pre

ferr

ed

Co

ntr

oller

Ch

oic

e

Oth

er

co

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op

tio

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Reliever = PRN SABA

Add

Azithromycin?

IMPACT Trial

• N = 10,355 adults aged 40+ with CAT score of ≥ 10 plus • FEV1 <50% predicted and history of at least one exacerbation in

previous year, or

• FEV1 50-80% predicted and history of at least two exacerbations in previous year

• 52 weeks

• Randomized, double-blind, parallel-group • Fluticasone furoate/umeclidinium/vilanterol 100/62.5/25 mcg once

daily

• Fluticasone furoate/vilanterol 100/25 mcg once daily

• Umeclidinium/vilanterol 62.5/25 mcg once daily

• Primary outcome = annual rate of moderate or severe exacerbations

David Lipson, et.al. Once-daily single-inhaler triple versus dual therapy in patients with COPD. NEJM . April 18,2018.

COPD Assessment

GOLD. Pocket guide to COPD diagnosis, management, and prevention. 2018.

Results

David Lipson, et.al. Once-daily single-inhaler triple versus dual therapy in patients with COPD. NEJM . April 18,2018.

Confirms GOLD Guidelines for Group D,

but questions group C or B?

Group C

Group A

Group D

Group B

GOLD. Pocket guide to COPD diagnosis, management, and prevention. 2018.

Put all the pieces together…patient case

• 48 y/o male with asthma comes to clinic c/o cough

• PMH: Former smoker (quit 3 months ago), HTN, allergic rhinitis. Has had 2 ED visits for asthma exacerbations in last six months

• Current medications: • Symbicort 160/4.5 2 puffs two

times per day (pt admits that he forgets second dose often)

• Albuterol inhaler 2 puffs every four hours as needed (currently using 3-4 times per day)

• Montelukast 10mg daily

• Fluticasone nasal spray 2 sprays each nostril once daily

• Lisinopril 10mg once daily

• Labs:

• ACT = 12

• Eosinophils: 300 cells/µL

• Spirometry: FEV1 = 60%

predicted; FEV1/FVC =

0.68

Patient case continued

• What may be contributing to patient’s symptoms?

• What medication changes would you make?

-ACE inhibitor causing cough?

-Poor inhaler technique/nonadherence?

-Undiagnosed COPD?

-Eosinophilia?

-Add LAMA?

-Switch Symbicort to once daily ICS/LABA?

-Educate on proper inhaler technique?

-Switch lisinopril to ARB?

-Add anti-IL5?

-Add Azithromycin 500mg three times a week?

Apply this to your practice…

• New treatments for asthma include tiotropium, biologics

• New inhaler devices include Respimat, Respiclick and

Ellipta

• AirDuo is first generic ICS/LABA

• Trelegy Ellipta – first once daily triple therapy

(ICS/LABA/LAMA) for COPD

• In future, watch for biologics to be approved for COPD

and possibly macrolide antibiotics for asthma