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Eosinophilic Asthma: Medications & ManagementApril 29,2021

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OUR SPEAKER

Disclosures: NONE

Disclaimer: Focus on FDA-approved treatments for Eosinophilic Asthma

Dr. Marissa Shams

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A Look at Eosinophilic-drivenDISEASES

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A few facts about asthma

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NHLBI. Expert Panel Report 3: Guidelines for the Diagnosis and Management of Asthma. No. 08-4051. 2007.

Inflammation

Airway hyper-responsiveness

Reversible airway obstruction

Clinical symptoms(cough, wheezing, dyspnea)

Environmental and genetic factors

Asthma is a syndromerather than a single disease!

Understanding Asthma

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What is Asthma?

Chronic obstructive inflammatory lung “syndrome”

Recurrent episodes of wheeze, cough, shortness of breath and chest tightness

Symptoms vary over time and in intensity

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What is Asthma?

Confirmed airflow obstruction:

•Spirometry with positive response to bronchodilator “reversibility”•Positive bronchial challenge test (Methacholine or Exercise test)

Inflammatory cells infiltrate airways: edema, thickened mucus, bronchospasm

Heterogeneous mix of subtypes “phenotypes”

•Allergic Asthma•Aspirin Exacerbated Respiratory Disease•Eosinophilic Asthma•TH2-Low Asthma

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Asthma Phenotypes & Assessment

Phenotype: unique pathophysiology that drive symptoms, mucosal inflammation and airway smooth muscle contraction

Phenotype assessment:

• Co-Morbidity• Induced sputum analysis• Bronchoscopy• Complete blood cell count (AEC) • Serum IgE• Environmental allergy assessment (spt, sIgE)• FeNO (fractional exhaled Nitric Oxide)

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What is Eosinophilic Asthma?

§ Develops in adulthood§ Severe & persistent form of asthma§ Frequent exacerbations§ Refractory symptoms despite steroids § Fixed airway obstruction§ Eosinophil inflammation within the

airwaysü Lung tissue or sputum (Bronchoscopy)ü Peripheral blood is a surrogate marker

§ Co-Morbidities: ü Chronic Sinusitis & Nasal Polyposis ü Aspirin / NSAID Hypersensitivity

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Asthma Management: Assessing Control

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Asthma Management: Treatment

Goal of Treatment: Reduce symptoms and flares, Improve quality of life, Maintain control• Short Acting-Bronchodilator:

• As needed for symptoms• Inhaled Steroids (+/- Long Acting-Bronchodilator):

• Oral thrush, dysphonia• Oral Corticosteroids:

• Greater bioavailability of medication• Increased risk of side effect with higher doses and longer duration of use• Easy bruising, osteoporosis, cataracts, glaucoma, adrenal suppression, diabetes, hypertension

• Biologic Therapies:• Precision therapies that target the specific source of inflammation • Reduction in exacerbations & symptoms, Improvement in quality of life• Taper / Discontinue use of oral glucocorticoids• Indication: severe asthma, adherent to high-dose inhaled steroids, frequent flares

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© Global Initiative for Asthma, www.ginasthma.orgGINA 2020, Box 3-4A

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Biologic Therapies for Eosinophilic Asthma

Route Frequency Target Biomarker Side effects Other indications

Mepolizumab(Nucala)

SC q4weeks Binds IL-5; reduction in eosinophil production and survival

EAC Herpes ZosterAnaphylaxis / Hypersensitivity Parasite infection

EGPAHES

Reslizumab(Cinquair)

IV q4weeks (weight based dosing)

Binds IL-5; reduction in eosinophil production and survival

EAC Anaphylaxis / HypersensitivityParasite infection

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Benralizumab(Fasenra)

SC q4weeks x 3; q8 weeks

Binds IL-5 receptor, reduction in eosinophil production and survival, activates NK to induce apoptosis of eosinophils & basophils

EAC Anaphylaxis / HypersensitivityParasite infection

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Dupilumab(Dupixient)

SC q2 weeks Binds IL-4 receptor a subunit, inhibit IL-4 & IL-13 cytokines

EAC,FeNO,Oral steroid dependence

Anaphylaxis / HypersensitivityKeratitis

Atopic Dermatitis, Chronic Sinusitis w/ Nasal Polyposis

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Mechanism of Biologic Therapies

WAO Journal 2018

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Questions posed by Biologic Therapies

• Which is the most effective? ?• Best biomarkers to predict effective response??• Therapeutic non-responders: when to switch / stop

medications? ?• Combination of biologic agents or combination of

targets??• Length of treatment? ?• New agents in development?

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Risk Factors for Exacerbations

Poor asthma control

Lack of medication adherence

Incorrect inhaler technique

Smoking

Exposure to triggers

Uncontrolled co-morbid disease

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Inhaler technique is crucial

Metered Dose Inhalers

Dry Powder Inhalers

Breath-actuated devices

Respimat devices

VHC / Spacers

Nebulizer

Allergy & Asthma Network is a national nonprofit organization dedicated to ending needless death

and suffering due to asthma, allergies and related conditions through outreach, education, advocacy

and research.

Short-acting Long-acting

Short-acting Long-acting

relax tight muscles in airways and offer quick relief of symptoms such as coughing, wheezing and shortness of breath for 3-6 hours muscles in airways and offer lasting relief of symptoms such as coughing, wheezing and shortness of breath for at least 12 hours

SHORT-ACTING BETA2-AGONIST BRONCHODILATORS LONG-ACTING BETA2-AGONIST BRONCHODILATORS relax tight

INHALED CORTICOSTEROIDS reduce and prevent swelling of airway tissue; they do not relieve sudden symptoms of coughing, wheezing or shortness of breath

contains inhaled corticosteroid, COMBINATION MEDICATIONS contain both long-acting beta2-agonist (LABA) long-acting beta2-agonist (LABA) and

MUSCARINIC ANTAGONIST (ANTICHOLINERGIC) COMBINATION MEDICATIONS

relieve cough, sputum production, wheeze and chest tightness associated with chronic lung diseases contains muscarinic antagonist and beta2-agonist

contain both inhaled corticosteroid and long-acting beta2-agonist (LABA) and long-acting muscarinic antagonist (LAMA) long-acting muscarinic antagonist (LAMA)

BIOLOGICS target cells and pathways that cause airway inflammation; delivered by injection or IV BRONCHIAL THERMOPLASTY PDE4 INHIBITORS

ease lung inflammation and reduce exacerbations

Respiratory Treatments2021

©2021 Allergy & Asthma Network Reviewed by Dennis Williams, PharmD

ProAir® Digihaler™

117 mcgalbuterol sulfate

ProAir® HFA100 mcgalbuterol sulfate

ProAir RespiClick® 117 mcgalbuterol sulfate inhalation powder

Ventolin® HFA 90 mcgalbuterol sulfate

Serevent® Diskus® 50 mcgsalmeterol xinafoate inhalation powder

Xopenex HFA® 59 mcglevalbuterol tartrate

Striverdi®

Respimat®

2.5 mcgolodaterol hydrochloride

ArmonAir® RespiClick® 55, 113, 232 mcgfluticasone propionate inhalation powder

ArmonAir® Digihaler™ 55, 113, 232 mcgfluticasone propionate inhalation powder

Asmanex® Twisthaler® 110, 220 mcgmometasone furoate inhalation powder

Asmanex® HFA 100, 200 mcgmometasone furoate

Flovent® Diskus® 50, 100, 250 mcg fluticasone propionate inhalation powder

Flovent® HFA 44, 110, 220 mcgfluticasone propionate

Pulmicort Flexhaler® 90, 180 mcgbudesonide inhalation powder

QVAR® Redihaler™ 40, 80 mcg beclomethasone dipropionate

Arnuity® Ellipta®

50, 100, 200 mcgfluticasone furoate inhalation powderAlvesco®

HFA 80, 160 mcgciclesonide

Advair Diskus® 100/50, 250/50, 500/50 mcgfluticasone propionate and salmeterol inhalation powder

Advair® HFA45/21, 115/21, 230/21 mcgfluticasone propionate and salmeterol xinafoate

AirDuo® RespiClick®

55/14, 113/14, 232/14 mcgfluticasone propionate and salmeterol inhalation powder

AirDuo® Digihaler™

55/14, 113/14, 232/14 mcgfluticasone propionate and salmeterol inhalation powder

Anoro® Ellipta®

62.5/25 mcgumeclidinium and vilanterol inhalation powder

Bevespi Aerosphere® 9/4.8 mcgglycopyrrolate and formoterol fumarate

Breo® Ellipta®

100/25, 200/25 mcgfluticasone furoate and vilanterol inhalation powder

Dulera® 100/5, 200/5 mcgmometasone furoate and formoterol fumarate dihydrate

Symbicort® 80/4.5, 160/4.5 mcg budesonide and formoterol fumarate dihydrate

Wixela™ Inhub™ 100/50, 250/50, 500/50 mcg fluticasone propionate and salmeterol xinafoate (approved generic of Advair Diskus)

Stiolto™ Respimat®

2.5/2.5 mcgtiotropium bromide and olodaterol

Trelegy® Ellipta®

200/62.5/25 mcg, 100/62.5/25 mcgfluticasone furoate, umeclidinium and vilanterol inhalation powder

Breztri Aerosphere™

160/9/4.8 mcgbudesonide, glycopyrrolate and formoterol fumarate

= DOSE INDICATOR = GENERIC AVAILABLE DISEASE STATES: = ASTHMA = COPD

Atrovent® HFA 17 mcgipratropium bromide

Combivent® Respimat® 20/100 mcgipratropium bromide and albuterol

Duaklir® Pressair® 400, 12 mcgaclidinium bromide and formoterol fumarate dihydrate

Incruse® Ellipta® 62.5 mcgumeclidinium inhalation powder

Spiriva® HandiHaler®

18 mcgtiotropium bromide inhalation powder

Spiriva® Respimat® 1.25, 2.5 mcgtiotropium bromide

Tudorza™ Pressair™ 400 mcgaclidinium bromide inhalation powder

AllergyAsthmaNetwork.org800.878.4403

Xolair®

omalizumabNucala®

mepolizumab Daliresp®

250, 500 mcg roflumilastCinqair®

reslizumab

Fasenra™

benralizumab Dupixent®

dupilumab

A minimally invasive procedure that uses mild heat to reduce airway smooth muscle, leading to fewer severe asthma flares, ER visits, and days lost from activities. www.btforasthma.com

Proventil® HFA120 mcgalbuterol sulfate

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Non-Pharmacologic Treatment: Avoidance of Asthma Triggers

§ Irritants: smoke, diesel exhaust§ Air pollution: Indoor & Outdoor§ Strong odors / fragrance § Respiratory infection:

ü Annual influenza vaccinationü Pneumococcal vaccination

§ Exercise§ Stress or strong emotions (laughing, crying)§ Sudden change in air temperature or humidity

(cold air)§ Hormonal changes

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Non-Pharmacologic Treatment : Assessment & Treatment of Co-Morbid Disease

§ Chronic Sinusitis with or without Nasal Polyposis

§ Aspirin / NSAID Hypersensitivity§ Obesity§ Tobacco abuse§ Obstructive Sleep Apnea§ GERD§ Depression & Anxiety§ Allergic conditions: Allergic Rhinitis,

Atopic Dermatitis, Food Allergy

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Asthma Management: Follow-Up

Follow-Up

Assess

Adjust

Review Response

Initial Visit§ Confirmation of diagnosis if necessary§ Symptom control § Modifiable risk factors & comorbidity§ Lung function § Inhaler technique and adherence§ Non-pharmacological strategy§ Patient (and parent) preferences and goals

§ Symptom control, Exacerbation frequency§ Medication side effect§ Lung function§ Asthma medications (adjust up or down)§ Patient satisfaction

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Monitoring SymptomsExpiratory Peak Flow Meter: device measuring peak expiratory flow rate

Frequency of symptoms: • Nocturnal awakenings• Activity limitation• Use of rescue inhaler

Symptom tracker app• AsthmaTracker• Asthma Storylines

Frequency of exacerbations:• Need for systemic steroids• ED / UC / Hospital visits• History of intubation need

Determination of asthma control and treatment decisions

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Management of Asthma Exacerbation

When to call your physician

§ Asthma symptoms are worsening§ Asthma symptoms are not responding to

asthma action plan

When to call 911

§ Unable to take a good deep breath § You can only talk in short phrases§ Persistent cough§ Feel too exhausted to breath§ Increased work to breathe§ Easier to breathe when sitting & leaning

forward§ Lips and/or fingernails bluish-gray§ Sweating even though skin feels cold and

clammy

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Preparation for Physician Visit

Seek care of allergist/immunologist or pulmonologist

Symptom logs (apps, journals, pfm values)

Health records:

• Prior hospitalization & ED records• Prior medications including use of oral steroids

Bring all medications to your visit

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Discussion points with physician

§ Confirmation of asthma diagnosis§ Phenotype assessment indicated§ Treatment plan

ü Types of medications & indicationsü Frequency and duration of medicationü Inhaler techniqueü Medication side effectsü Patient preference

§ Asthma action plan & emergency asthma management

§ Determination if treatment is effective§ Frequency of follow-up visits§ Assessment of comorbidity

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EosAsthmaDigital Tool Kit

Eosasthma.org

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EosAsthma

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TIME FORQUESTIONS ?

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Resources for more information

§ Eos Asthma ToolKit§ Eosasthma.org

§ Asthma & Allergy Network§ Allergyasthmanetwork.org

§ American Partnership for Eosinophilic Disorders

§ https://apfed.org/

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For More Information

https://allergyasthmanetwork.org/

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