SHARING A BREATH Interdisciplinary Management of Patients With Severe Asthma
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SHARING A BREATH Interdisciplinary Management of Patients With Severe Asthma
Faculty
v Barbara P. Yawn, MD, MSc, FAAFP v Nick Hanania, MD
Adjunct Professor Associate Professor of Medicine
Department of Family and Community Health Director, Airways Clinical Research Center
University of Minnesota Pulmonary, Critical Care, and Sleep Medicine
Minneapolis, MN Baylor College of Medicine
Houston, TX
v Joel J. Heidelbaugh, MD, FAAFP, FACG v Michael E. Wechsler, MD, MMSc
Professor Professor, Department of Medicine
Department of Family Medicine Co-Director, The Cohen Family Asthma Institute
Director of Medical Student Education Division of Pulmonary, Critical Care and Sleep
University of Michigan Medical School Medicine
Ann Arbor, MI Director, Asthma Program
National Jewish Health
2
Denver, CO
Disclosures v Barbara Yawn, MD, MSc FAAFP serves as a consultant for AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, and Novartis. v Nick Hanania, MD serves on the Advisory Board for AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Sanofi, and Mylan. Dr. Hanania also serves as a researcher for AstraZeneca, Boehringer Ingelheim, and GlaxoSmithKline. v Joel J. Heidelbaugh, MD, FAAFP, FACG has no financial relationships to disclose. v Michael E. Wechsler, MD, MMSc serves as a consultant and contracted research member for AstraZeneca, GlaxoSmithKline, Novartis, Regeneron, Sanofi, and TEVA. 3
Learning Objectives v Identify patients with asthma who may be appropriate candidates for specialist follow-up based on ongoing symptoms, exacerbation history, and treatment responses; v Discuss biologic options that have been approved by the US Food and Drug Administration for the treatment of severe asthma; v Coordinate the management of patients with severe asthma who require multidisciplinary care to maximize symptom control, reduce exacerbation risks, and minimize medication-related toxicities; v Educate patients with severe asthma about disease-related risks, long-term treatment options, and information related to adherence and self-management. 4
PRE-TEST QUESTIONS 5
Pre-test ARS Question 1 Pre-AS1: How often do you (or someone in your office) CURRENTLY evaluate asthma symptom control using a validated questionnaire such as the Asthma Control Test or Asthma Apgar? 1. At every patient visit 2. At 75% of patient visits 3. At 50% of patient visits 4. At 25% of patient visits 5. Never 6. I do not treat patients with asthma 6
Pre-test ARS Question 2 Pre-AS2: A 37-year-old man has had 2 asthma exacerbations in the last 8 months despite using a high-dose inhaled corticosteroid and a long- acting β2-angonist daily. You refer this patient to a local asthma specialist. Which of the following tests will your colleague most likely order to determine if a biologic therapy targeting the IL-5 signaling pathway is appropriate for this patient? 1. Exhaled nitric oxide 2. Periostin level 3. Blood eosinophil count 4. High-resolution computed tomography of the chest 7
Pre-test ARS Question 3 Pre-AS3: Which of the following groups of biologic therapy FDA-approved for severe asthma has been designed to block signaling by interleukin (IL)-5? 1. Benralizumab, dupilumab, reslizumab 2. Benralizumab, mepolizumab, reslizumab 3. Dupilumab, mepolizumab, reslizumab 4. Mepolizumab, omalizumab, reslizumab 8
Identifying Patients with
Severe Asthma
Michael E. Wechsler, MD, MMSc
9Severe Asthma
Estimated Prevalence, 2015 Definition From the ATS and ERS4
v Asthma in patients aged ≥6 years that
would be uncontrolled if not for
§ High-dose ICS plus a LABA or
leukotriene modifier/theophylline
Severe for the previous year
Asthma2-4
§ Systemic corticosteroids for
Mild-to-Moderate Asthma ≥50% of the year
v Asthma that is uncontrolled despite
these therapies
ATS, American Thoracic Society; ERS, European Respiratory Society; ICS, inhaled corticosteroid; LABA, long-acting β2 -agonist.
1. American Lung Association. Asthma in adults fact sheet. www.lung.org/lung-health-and-diseases/lung-disease-lookup/asthma/learn-
about-asthma/asthma-adults-facts-sheet.html. Accessed February 10, 2019; 2. Busse WW, et al. J Allergy Clin Immunol.
10 2000;106(6):1033-1042; 3. Lang DM. Allergy Asthma Proc. 2015;36(6):418-424; 4. Chung KF, et al. Eur Respir J. 2014;43(2):343-373.Severe Asthma
Estimated Prevalence, 2015 Definition From the ATS and ERS4
Approximately 25 Million Americans v Asthma in patients aged ≥6 years that
Have Asthma1 would be uncontrolled if not for
§ High-dose ICS plus a LABA or
leukotriene modifier/theophylline
Severe for the previous year
Asthma2-4
OR
§ Systemic corticosteroids for
Mild-to-Moderate Asthma ≥50% of the year
v Asthma that is uncontrolled despite
these therapies
ATS, American Thoracic Society; ERS, European Respiratory Society; ICS, inhaled corticosteroid; LABA, long-acting β2 -agonist.
1. American Lung Association. Asthma in adults fact sheet. www.lung.org/lung-health-and-diseases/lung-disease-lookup/asthma/learn-
about-asthma/asthma-adults-facts-sheet.html. Accessed February 10, 2019; 2. Busse WW, et al. J Allergy Clin Immunol.
11
2000;106(6):1033-1042; 3. Lang DM. Allergy Asthma Proc. 2015;36(6):418-424; 4. Chung KF, et al. Eur Respir J. 2014;43(2):343-373.Uncontrolled vs Severe Asthma
v “Asthma may be considered
uncontrolled either because of
persistence of symptoms despite
appropriate treatment, or due to
poor adherence to therapy or use of
inhaler devices.”1
v “Severe asthma is asthma that is
uncontrolled despite adherence
with maximal optimized therapy
and treatment of contributory
factors, or that worsens when high-
dose treatment is decreased.”2
GINA, Global Initiative for Asthma. 1. Skolnik NS, et al. Curr Med Res Opin. 2019 Mar
18:1. 2. [Epub ahead of print]. GINA. Difficult-to-treat and severe asthma in
adolescents and adult patients. Diagnosis and Management.
https://ginasthma.org/wp-content/uploads/2019/04/GINA-Severe-asthma-Pocket-
12 Guide-v2.0-wms-1.pdf. Accessed April 15, 2019.Factors That Can Contribute to Uncontrolled Asthma
Disease-Related Factors
Patient-Related Factors
• Cyclical nature of disease
• Comorbidities (eg, GERD,
• Increased disease severity rhinosinusitis, depression)
Environmental Factors • Differing asthma phenotypes • Smoking
• Passive smoking • Obesity
• Frequent exposure to • Age
Uncontrolled Asthma • Psychosocial issues (eg, lower
traffic or air pollution
• Outdoor and indoor income, poor health literacy)
allergens • Poor treatment adherence
Physician-Related Factors • Inadequate inhaler technique
• Medication underprescribing • Heterogeneity of treatment
• Failure to assess adherence response
• Failure to assess inhaler technique • Failure to follow self-management
plan
• Misdiagnosis
• Side effects of other medications
• Lack of asthma action plan (eg, NSAIDs)
• Absence of specialty care
GERD, gastroesophageal reflux disease; NSAID, nonsteroidal anti-inflammatory drug.
13 Adapted from Wechsler ME. Am J Med. 2014;127(11):1049-1059.Factors That Can Contribute to Uncontrolled Asthma
Disease-Related Factors
Patient-Related Factors
Cyclical phenotypes
• Assess nature of disease
• Comorbidities (eg, GERD
Increased
• Match disease
treatment to severity
asthma rhinosinusitis, depression)
Environmental Factors Differing asthma phenotypes
• phenotype Smoking comorbid conditions
•• Manage
• Passive smoking •–Obesity
Depression
• Frequent exposure to •–Age
GERD
• Reduce Controlled Asthma?
traffic orexposure to
air pollution •–Psychosocial
Rhinitis issues (eg, lower
• allergic
Outdoortriggers
and indoor income, poor health literacy)
– Sinusitis
allergens • Poor treatment adherence
Physician-Related Factors •• Encourage
Inadequateweight
inhalerloss
technique
•• Emphasize treatment adherence
Heterogeneity of treatment
• Medication under-prescribing • Educate
• Assess
Failure and address
to assess adherence and
adherence responseabout correct inhaler
Failure to
• inhaler assess inhaler technique • technique
Failure to follow self-management
technique plan
Misdiagnosis
• Refer • Smoking cessation
for specialty care • Side effects of other medications
Lack of asthma
• Develop action
an asthma plan plan
action (eg, NSAIDs)
• Absence of specialty care
14 Adapted from Wechsler ME. Am J Med. 2014;127(11):1049-1059.Poor Adherence to Asthma Therapies
Surprising Statistics
50
~
of medications
%
82
of patients with
%
11
of patients in
%
prescribed for asthma do not clinical trials used
asthma are taken fill their ICS less than 80% of
by patients1 prescriptions2 their medications3
1. Bender B, et al. Ann Allergy Asthma Immunol. 1997;79(3):177-185; 2. Williams LK, et al. J Allergy Clin Immunol. 2007;120(5):1153-1159;
15 3. Bateman ED, et al. Am J Respir Crit Care Med. 2004;170(8):836-844.A Case Example v 23-year-old man with diagnosed asthma v Controller treatment regimen includes daily high-dose ICS plus a LABA that he refills monthly v Experienced 2 exacerbations requiring an OCS within the last year v Reports awakening 1 night/week owing to cough and chest tightness v Uses rescue albuterol for daily wheezing v Spirometry results; FEV1
A Case Example v 23-year-old man with diagnosed asthma v Controller treatment regimen includes daily high-dose ICS plus a LABA that he refills monthly v Experienced 2 exacerbations requiring an OCS within the last year v Reports awakening 1 night/week owing to cough and chest tightness v Uses rescue albuterol for daily wheezing v Spirometry results; FEV1
Assessment of
Asthma Control
Barbara Yawn, MD, MSc, FAAFP
18PRACTICE PEARL
What key points are demonstrated
in this patient-clinician encounter?
20Best Practices in Patient Evaluation
a. Consider differential
Confirm asthma diagnosisa diagnosis
21 Aaron SD, et al. Respir Crit Care Med. 2018;198(8):1012-1020; Bender B, et al. Ann Allergy Asthma Immunol. 1997;79(3):177-185.Best Practices in Patient Evaluation
a. Consider differential
Confirm asthma diagnosisa diagnosis
b. Employ standardized
Assess disease severityb questionnaires and inquire
about rescue inhaler use
22 Aaron SD, et al. Respir Crit Care Med. 2018;198(8):1012-1020; Bender B, et al. Ann Allergy Asthma Immunol. 1997;79(3):177-185.Best Practices in Patient Evaluation
a. Consider differential
Confirm asthma diagnosisa diagnosis
Assess disease severityb
b. Employ standardized
Evaluate triggers that questionnaires and inquire
about rescue inhaler use
affect asthma
Evaluate comorbid states that
affect asthma
23 Aaron SD, et al. Respir Crit Care Med. 2018;198(8):1012-1020; Bender B, et al. Ann Allergy Asthma Immunol. 1997;79(3):177-185.Best Practices in Patient Evaluation
a. Consider differential
Confirm asthma diagnosisa diagnosis
Assess disease severityb
b. Employ standardized
Evaluate triggers that questionnaires and inquire
about rescue inhaler use
affect asthma
Evaluate comorbid states that c. Inhaler technique is
affect asthma suboptimal in many patients
Assess treatment adherence
and inhaler techniquec
24 Aaron SD, et al. Respir Crit Care Med. 2018;198(8):1012-1020; Bender B, et al. Ann Allergy Asthma Immunol. 1997;79(3):177-185.Under- and Overdiagnosis of Asthma
Underdiagnosis Overdiagnosis of current asthma
• Lack of any diagnosis • Another condition that causes
• Asthma misdiagnosed as another respiratory symptoms misdiagnosed as
condition that causes respiratory asthma
symptoms • Patient has asthma that is in sustained
clinical remission
v Underdiagnosis results in poorer health-related QoL and more work and school
absenteeism
v Overdiagnosis can lead to unnecessary use of medications, burden of increased
drug costs, and a delay in identifying the true cause of respiratory symptoms
25 Aaron SD, et al. Am J Respir Crit Care Med. 2018;198(8):1012-1020.Conditions Commonly Misdiagnosed as
Asthma in Adults
v COPD
v Hyperventilation with panic attacks
v Bronchiolitis
v Congestive heart failure
v Adverse drug reaction
v Bronchiectasis, cystic fibrosis
v Hypersensitivity pneumonitis
26
ACE, angiotensin-converting enzyme; COPD, chronic obstructive pulmonary disease.Conditions Commonly Misdiagnosed as
Asthma in Adults
v COPD v Hypereosinophilic syndromes
v Hyperventilation with panic attacks v Pulmonary embolus
v Bronchiolitis v Herpetic tracheobronchitis
§ (Constrictive/proliferative) v Endobronchial lesion or foreign body
v Congestive heart failure v Allergic bronchopulmonary
v Adverse drug reaction aspergillosis
§ (eg, ACE inhibitors, β-blockers) v Acquired tracheobronchomalacia
v Bronchiectasis, cystic fibrosis v Churg-Strauss syndrome
v Hypersensitivity pneumonitis
27
ACE, angiotensin-converting enzyme; COPD, chronic obstructive pulmonary disease.Determining Asthma Control
Patients Aged ≥12 Years
Components of Controla Not Well Controlled Very Poorly Controlled
Symptoms >2 days/week Throughout the day
Nighttime awakenings 1-3×/week ≥4×/week
Interference with normal activity Some limitation Extremely limited
Rescue inhaler use >2 days/week Several times/day
60%-80%
FEV1/peak flowAssessment Tools to Evaluate Asthma Symptom Control
Asthma Control Asthma Control
Test (ACT)1 Questionnaire (ACQ)2
Asthma Therapy Asthma APGAR PLUS
Assessment Questionnaire Questionnaire4
(ATAQ)3
For links to these assessment tools and other resources,
please visit: www.ExchangeCME.com/AsthmaResources19.
1. Nathan RA, et al. J Allergy Clin Immunol. 2004;113(1):59-65; 2. Juniper EF, et al. Eur Respir J. 1999;14(4):902-907;
29 3. Vollmer WM, et al. Am J Respir Crit Care Med. 1999;160(5 Pt 1):1647-1652. 4. Yawn BP, et al. Ann Fam Med. 2018;16(2):100-110.Sample Follow-up Questions
Activities of Daily Living
What have you given
up because of your asthma?
30Sample Follow-up Questions
Activities of Daily Living Medication Regimen
What have you given What do you think is the
up because of your asthma? difference between your rescue
and controller medications?
Disease Persistence Treatment Response
Has the frequency or severity Why do you think your asthma
of your daytime symptoms therapy is not working well?
remained relatively consistent
over the last 2 months?
31Consider the Role of Potential Asthma Triggers
vIrritants vAllergens
§ Tobacco and wood smoke § Pollens
§ Particulates, pollution § Mold
§ Gas or diesel fumes § Animal dander
vOccupational factors § Insects
§ Chemicals vConcomitant medications
§ Fumes § NSAIDs, β-blockers
NSAID, nonsteroidal anti-inflammatory drug.
Centers for Disease Control and Prevention. Environmental triggers of asthma. https://www.atsdr.cdc.gov/csem/csem.asp?csem=32&po=6. Accessed February 10, 2019; Wechsler
ME. Am J Med. 2014;127(11):1049-1059; Morales DR, et al. BMC Medicine. 2017;15(1):18; American Academy of Allergy, Asthma, and Immunology. Medications may trigger
32 asthma symptoms. https://www.aaaai.org/conditions-and-treatments/library/asthma-library/medications-that-can-trigger-asthma-symptoms. Accessed February 10, 2019.Asthma Management Algorithm
Severity
Treatment
Asthma Control
Management • Impairment
• Risk
Modifications • Lung function
Inadequate Adequate
• Nonadherence
• Asthma triggers
Asthma Control • Comorbidities
Inadequate: Why? • Psychosocial issues
• Incorrect inhaler technique
33 Courtesy of Dr. Barbara Yawn.Advanced Therapies for
Severe Asthma
Michael E. Wechsler, MD, MMSc
34Unmet Needs in Patients With Asthma
v Careful assessment of current adherence to asthma guideline recommendations is
an important first step when considering an asthma biologic
§ 28% of patients who had uncontrolled asthma failed to improve after 1 year of guideline-
recommended care1
v Even after ensuring guideline/medication adherence, considering safety of these
agents, and using available biomarkers to estimate treatment response, patient
access to the biologic is needed2
Prescribers of biologics for asthma should consider how best to assess
and improve medication adherence to ICS/LABA before considering
the use of a biologic agent.2
LABA, long-acting β-agonist; ICS, inhaled corticosteroid.
35 1. Bateman ED, et al. Am J Respir Crit Care Med. 2004;170(8):836-844; 2. Rank MA, Oppenheimer JJ. Ann Allergy Asthma Immunol. 2019;122(4);358-359.Kira, 4 Months Later v New regimen includes a combination ICS/LABA v Recent episode of “bronchitis” sent Kira her to an urgent care clinic while she was out of town, where she was prescribed a course of prednisone and an antibiotic v Continues to use her rescue inhaler 4 or 5 times weekly v Has canceled activities and plans arising from daytime and nighttime asthma symptoms v Kira and her physician confirm together that she is using her medications properly, and confirm that any asthma triggers are under control 36
PRACTICE PEARL
What is the most appropriate next step
for Kira and her physician to help
control Kira’s asthma symptoms?
37Stepwise Approach to Asthma Management
STEP 1 STEP 2 STEP 3 STEP 4 STEP 5
High-dose ICS+LABA
Daily low-dose Refer for phenotypic
PREFERRED As-needed ICS or as- assessment
low-dose Low-dose ICS Medium/high-dose
CONTROLLER ICS- needed low-
+LABA ICS+LABA
± add-on therapy, eg,
OPTIONS formoterol dose ICS- tiotropium, anti-IgE,
formoterol anti-IL5/5R,
anti-IL4R
Low-dose ICS LTRA, or low -
Medium-dose High-dose ICS, add-
Other Controller taken dose ICS taken Add low-dose OCS, but
ICS, or low-dose on tiopropium, or
Options whenever whenever consider side effects
ICS+LTRA add-on LTRA
SABA is taken SABA taken
Other Reliever
As-needed low-dose ICS-formoterol
Option
As-needed
Each step requires Patientshort-acting
education β2 and
-agonist (SABA)
efforts to
address modifiable risk factors and comorbidities.
IgE, immunoglobulin E; LTRA, leukotriene receptor antagonist; OCS, oral corticosteroid; SABA, short-acting β2-agonist.
38 Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2019. Available from: www.ginasthma.org.Stepwise Approach to Asthma Management
STEP 1 STEP 2 STEP 3 STEP 4 STEP 5
High-dose ICS+LABA
Daily low-dose Refer for phenotypic
PREFERRED As-needed ICS or as- assessment
low-dose Low-dose ICS Medium/high-dose
CONTROLLER ICS- needed low-
+LABA ICS+LABA
± add-on therapy, eg,
OPTIONS formoterol dose ICS- tiotropium, anti-IgE,
formoterol anti-IL5/5R,
anti-IL4R
Low-dose ICS LTRA, or low -
Medium-dose High-dose ICS, add-
Other Controller taken dose ICS taken Add low-dose OCS, but
ICS, or low-dose on tiopropium, or
Options whenever whenever consider side effects
ICS+LTRA add-on LTRA
SABA is taken SABA taken
Other Reliever
As-needed low-dose ICS-formoterol
Option
As-needed
Each step requires Patientshort-acting
education β2 and
-agonist (SABA)
efforts to
address modifiable risk factors and comorbidities.
IgE, immunoglobulin E; LTRA, leukotriene receptor antagonist; OCS, oral corticosteroid; SABA, short-acting β2-agonist.
39 Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2019. Available from: www.ginasthma.org.Biomarkers
Their Role in Asthma Phenotyping
Blood eosinophils FeNO IgE
FeNO, fractional exhaled nitric oxide.
Kim MA, et al. Curr Opin Allergy Clin Immunol. 2014;14(1):49-54; Chung KF, et al. Eur Respir J. 2014;43(2):343-373; Global Initiative
40 for Asthma. Global Strategy for Asthma Management and Prevention, 2018. www.ginasthma.org. Accessed February 10, 2019.Basis for Biologic Therapies
Type 2 Inflammation
Antigens
TSLP
CRTh2
IL-13
Th2 ILC2
cell IL-4, IL-5, IL-13 CRTh2
GATA3 GATA3
IL-4 GM-CSF IL-5
B cell CRTh2
Leukotrienes
PGD2
IgE Histamine
IL-3, IL-4, IL-5, IL-9 Eosinophil
Mast cell
ALX, lipoxin A4 receptor; BLT2, leukotriene B receptor 2; CRTh2, chemoattractant receptor homologue from Th2 cells; CXCL8, CXC motif
chemokine ligand 8; CXCR2, CXC motif chemokine receptor 2; GATA3, GATA binding protein 3; GM-CSF, granulocyte–macrophage colony-
stimulating factor; IFN-γ, interferon gamma; IgE, immunoglobulin E; IL, interleukin; ILC2, innate lymphoid cells; PGD2, prostaglandin D2;
TSLP, thymic stromal lymphopoietin; TGF-β, transforming growth factor β; Th, T helper; TNF, tumor necrosis factor.
41
Adapted from Israel E, Reddel HK. N Engl J Med. 2017;377(10):965-976.Basis for Biologic Therapies
Type 2 Inflammation Non–Type 2 Inflammation
Irritants, pollutants, microbes,
Antigens and viruses
TSLP IL-25 IL-33 IL-6 CXCL8
CRTh2 TGF-β GM-CSF
IL-13
Th2 Th17 IL-23 Th1
cell ILC2 cell cell
IL-4, IL-5, IL-13 CRTh2
GATA3 GATA3 IFN-γ
IL-6 TNF
IL-4 GM-CSF IL-5
CRTh2 IL-17
B cell Leukotrienes Leukotrienes B4
IL-8 CXCR2
PGD2
IgE Histamine
Lipoxin
BLT2
IL-3, IL-4, IL-5, IL-9 Eosinophil ALX Neutrophil
Mast cell
ALX, lipoxin A4 receptor; BLT2, leukotriene B receptor 2; CRTh2, chemoattractant receptor homologue from Th2 cells; CXCL8, CXC motif
chemokine ligand 8; CXCR2, CXC motif chemokine receptor 2; GATA3, GATA binding protein 3; GM-CSF, granulocyte–macrophage
colony-stimulating factor; IFN-γ, interferon gamma; IgE, immunoglobulin E; IL, interleukin; ILC2, innate lymphoid cells; PGD2,
prostaglandin D2; TSLP, thymic stromal lymphopoietin; TGF-β, transforming growth factor β; Th, T helper; TNF, tumor necrosis factor.
42 Adapted from Israel E, Reddel HK. N Engl J Med. 2017;377(10):965-976.FDA-Approved Biologic Agents for Severe Asthma
Anti-IgE Anti-IL-5/IL-5Rα Anti-IL-4Rα Therapy
Therapy Therapies
IL-5 Mepolizumab IL-4 IL-4 OR IL-13
B cell Reslizumab
Benralizumab
IgE
Omalizumab
IL-5Rα bc Dupilumab Dupilumab
IL-4Rα γc IL-4Rα IL-13Rα1
IL-5 regulates eosinophil IL-4 mediates IgE production, Th2-cell
Mast cell proliferation, differentiation, differentiation, B-cell growth, and
migration, and survival eosinophil recruitment
FDA, US Food and Drug Administration; IgE, immunoglobulin E; IL, interleukin; IL-4Rα, interleukin-4 receptor α; IL-5Rα, interleukin-5 receptor α; IL-
13Rα1, interleukin-13 receptor α1; Th, T helper.
43
Adapted from Darveaux J, et al. J Allergy Clin Immunol Pract. 2015;3(2):152-161 and Gandhi NA, et al. Nat Rev Drug Discov. 2016;15(1):35-50.Omalizumab
Anti-IgE mAb
1.6
v Approved for patients aged 1.47
≥6 years with1 1.4 38.3%
Annual Exacerbation Rate2
RR vs placebo
§ Moderate-to-severe 1.2
persistent asthma
1.0 0.91a
§ A positive skin test or
in vitro reactivity to a 0.8
perennial aeroallergen 0.6
§ Inadequate control with ICS
0.4
v SQ administration1
0.2
§ Based on pretreatment serum IgE
level and body weight1 0.0
Control Omalizumab
Pooled Clinical Study Data
a
PMepolizumab
Anti-IL-5 mAb
2.0
v ≥2 exacerbations within 1.74 53%
Annual Exacerbation Rate1
the last year RR vs placebo
1.5
v High blood eosinophils
§ ≥150 cells/μL at screening
OR ≥300 cells/μL during 1.0 0.83a
the prior year
v Treated with high-dose ICS 0.5
plus another controller
0.0
Placebo (n=191) Mepolizumab (n=194)
Approved as add-on maintenance therapy for patients aged ≥12 years
with severe eosinophilic asthma; SQ administration.2
aPReslizumab
Anti-IL-5 mAb
2.0
v ≥1 exacerbation within the last year 1.81 50%-59%
Annual Exacerbation Rate1
v High blood eosinophils RR vs placebo
1.5
§ ≥400 cells/μL at screening
v Treated with medium- to 1.0 0.84a
high-dose ICS and up to
1 other controller drug
0.5
0.0
Placebo (n=476) Reslizumab (n=477)
Approved as add-on maintenance therapy for patients aged ≥18 years
with severe eosinophilic asthma; IV administration.2
aPBenralizumab
Anti-IL-5Rα mAb
v ≥2 exacerbations 2.0
51% Placebo
28%
Annual Exacerbation
Benralizumab
within the last year 1.5 RR RR
1.33 vs placebo vs placebo
v Treated with
Rate1,2
0.93
medium- to high- 1.0
0.65a 0.66b
dose ICS plus LABA
0.5
0.0
SIROCCO CALIMA
≥300 Eosinophils/μL
Approved as add-on maintenance therapy for patients aged ≥12 years with
severe eosinophilic asthma; SQ administration.3
aPDupilumab
Anti-IL-4Rα mAb
v Treatment with a systemic steroid for
1.2
-48% -46%
Annual Exacerbation Rate1
worsening asthma at least once in the 1.0
RR
vs placebo
0.97 RR
vs placebo
0.87
last year
0.8
v Hospitalization or emergency medical
care visit for worsening asthma 0.6
0.46a
0.52a
0.4
0.2
0.0
Placebo Dupilumab Placebo Dupilumab
200 mg 300 mg
Approved as add-on maintenance therapy for patients aged ≥12 years with
moderate-to-severe eosinophilic or OCS-dependent asthma; SQ administration.2
aPEmerging Agent: Tezepelumab
Phase 2b Trial With an Anti-TSLP mAb
Anti-TSLP Therapy 1.0 61% 71% 66%
Annual Exacerbation Rate
RR RR RR
TSLP Tezepelumab vs placebo vs placebo vs placebo
0.8
0.67
0.6
TSLPR IL-7Rα
0.4
0.26a
0.19a 0.22a
0.2
TSLP regulates type 2 immune
responses by activating dendritic 0.0
cells, ILC2 cells, T cells, and B cells Placebo Tezepelumab Tezepelumab Tezepelumab
70 mg Q4W 210 mg Q4W 280 mg Q2W
a
P≤0.001 versus placebo.
N=584 patients aged 18 to 75 years with ≥2 exacerbations or 1 severe exacerbation requiring hospitalization in the last year
despite medium- to high-dose ICS plus LABA were randomly assigned to receive SQ tezepelumab for 52 weeks.
IL-7Rα, interleukin-7 receptor α; TSLP, thymic stromal lymphopoietin; TSLPR, thymic stromal lymphopoietin receptor.
49
Corren J, et al. N Engl J Med. 2017;377(10):936-946.Safety of Biologics in Asthma
Most Commonly Reported Adverse Reactions Black Box
Biologic Agent
in Clinical Trials Warning
Benralizumab Headache, pharyngitis None
Dupilumab Injection-site reactions None
Mepolizumab Headache, injection-site reaction, back pain, fatigue None
Omalizumab Arthralgia, pain (general) Anaphylaxis
Reslizumab Oropharyngeal pain Anaphylaxis
50 Drugs@FDA: FDA Approved Drug Products. https://www.accessdata.fda.gov/scripts/cder/daf/.What Patients Need to Know About Biologic Therapies
for Severe Asthma
Biologic agents —
v Are used to treat uncontrolled moderate or severe asthma
v Do not cure asthma
v Are added to a patient’s current treatment regimen
v Must be taken regularly, like all asthma medicines
v Are injectable medications
§ Some biologics can be self-administered at home, whereas others must be administered
in a doctor’s office
51Multidisciplinary Management of
Severe Asthma
Barbara Yawn, MD, MSc, FAAFP
52Pre-test ARS Question 4 Pre-AS4: How many of your patients with asthma CURRENTLY have a written asthma action plan that you discuss at most of their appointments? 1. All of my patients with asthma 2. 75% of my patients 3. 50% of my patients 4. 25% of my patients 5. None of my patients 6. I do not treat patients with asthma 53
Asthma Action Plan 54 CDC. Asthma action plan. https://www.cdc.gov/asthma/actionplan.html. Accessed April 11, 2019.
Shared Decision Making/Goal Setting
Focus on Choice, Rather Than Change
“Healthcare professionals have a duty to inform people about the
benefits and harms of proposed interventions… Shared decision making
is defined by extending this duty to supporting people to arrive at
informed preferences, eliciting and respecting those preferences by
integrating them as decisions are made.”
Shared Decision-Making Tool
CHEST Foundation, Allergy and Asthma Network, ACAAI
ExchangeCME.com/SAResources19
55 Elwyn G, et al. Implement Sci. 2016;11:114.Pre-test ARS Question 5 Pre-AS5: According to the GINA recommendations, patients who require at least ______ course(s) of OCS within a year to control their asthma symptoms should be referred to an asthma specialist for evaluation. 1. 1 2. 2 3. 3 4. 4 56
Reducing Oral Corticosteroid Burden in
Patients With Asthma
32 -45
% %
of patients with severe
asthma require frequent,
and often daily, OCS1,2
T2DM, type 2 diabetes mellitus.
1. Moore WC, et al. J Allergy Clin Immunol. 2007;119(2):405-413; 2. Shaw DE, et al. Eur Respir J. 2015;46(5):1308-
1321; 3. Sweeney J, et al. Thorax. 2016;71(4):339-346; 4. Luskin AT, et al. Clinicoecon Outcomes Res. 2016;8:641-
648; 5. Sullivan PW, et al. J Allergy Clin Immunol. 2018;141(1):110-116; 6. Global Initiative for Asthma. Global
57 Strategy for Asthma Management and Prevention, 2018. Available from: www.ginasthma.org.Reducing Oral Corticosteroid Burden in
Patients With Asthma
32 -45
% %
of patients with severe
DID YOU
KNOW… 93%
of asthma registry patients with severe disease
asthma require frequent, had ≥1 condition linked to OCS exposure3-5
and often daily, OCS1,2 v T2DM v Weight gain
v Osteoporosis v Osteopenia
v Cataracts v Hypertension
v Dyspeptic disorders v Obstructive sleep apnea
T2DM, type 2 diabetes mellitus.
1. Moore WC, et al. J Allergy Clin Immunol. 2007;119(2):405-413; 2. Shaw DE, et al. Eur Respir J. 2015;46(5):1308-1321; 3. Sweeney J, et al. Thorax.
2016;71(4):339-346; 4. Luskin AT, et al. Clinicoecon Outcomes Res. 2016;8:641-648; 5. Sullivan PW, et al. J Allergy Clin Immunol. 2018;141(1):110-
58 116; 6. Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2018. Available from: www.ginasthma.org.Reducing Oral Corticosteroid Burden in
Patients With Asthma
32 -45
% %
of patients with severe
DID YOU
KNOW… 93%
of asthma registry patients with severe disease
asthma require frequent, had ≥1 condition linked to OCS exposure3-5
and often daily, OCS1,2 v T2DM v Weight gain
v Osteoporosis v Osteopenia
v Cataracts v Hypertension
v Dyspeptic disorders v Obstructive sleep apnea
As recommended in the GINA Report, patients with asthma who require
≥2 courses of OCS within a year to control their asthma symptoms
should be referred to a specialist for evaluation.6
T2DM, type 2 diabetes mellitus.
1. Moore WC, et al. J Allergy Clin Immunol. 2007;119(2):405-413; 2. Shaw DE, et al. Eur Respir J. 2015;46(5):1308-1321; 3. Sweeney J, et al. Thorax.
2016;71(4):339-346; 4. Luskin AT, et al. Clinicoecon Outcomes Res. 2016;8:641-648; 5. Sullivan PW, et al. J Allergy Clin Immunol. 2018;141(1):110-116; 6.
59 Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2018. Available from: www.ginasthma.org.Oral Corticosteroid–Sparing Strategies
Encouraging Results With Biologic Therapies
v Benralizumab1 v Mepolizumab3
§ Reduced OCS dose by 75% § Reduced OCS dose by 50%
(vs 25% with placebo) (vs 0% with placebo)
v Dupilumab2 v Omalizumab4
§ Reduced OCS dose by 70% § 79% of patients reduced OCS dose by
(vs 42% with placebo) ≥50% (vs 55% with placebo)
1. Nair P, et al. N Engl J Med. 2017;376(25):2448-2458; 2. Rabe KF, et al. N Engl J Med. 2018;378(26):2475-2485; 3. Bel EH, et al. N Engl J Med.
60 2014;371(25):1189-1197; 4. Soler M, et al. Eur Respir J. 2001;18(2):254-261.Overcoming Challenges With Treatment Adherence
v Assess for adherence v Reasons for nonadherence
§ Inspect medication dose counters § Inadequate access to medication
§ Check pharmacy refill records § Dissatisfaction with medication
delivery
§ Perceived adverse effects
§ Lack of improvement with medication
noted by patient
61Overcoming Challenges With Treatment Adherence
v Assess for adherence v Reasons for nonadherence
§ Inspect medication dose counters § Inadequate access to medication
• Breath-actuated devices are more § Dissatisfaction with medication
accurate delivery
§ Check pharmacy refill records § Perceived adverse effects
§ Lack of improvement with medication
noted by patient
Seek to understand and address reasons for low adherence.
62If You Have Asthma A Poster 63
Conclusions
v Identifying patients with poorly controlled, severe asthma is critical
v Targeted biologic therapies can improve symptoms, decrease exacerbation risks, and
improve QoL in certain patients who have severe asthma
§ An anti-IgE therapy is FDA approved for patients with moderate-to-severe, persistent
allergic asthma, a positive skin test or in vitro reactivity to a perennial aeroallergen, and
age/body weight serum IgE levels
§ Three biologics targeting IL-5 signaling are now FDA approved for patients with severe
eosinophilic asthma
§ A therapy targeting IL-4Rα is now FDA approved for patients with moderate-to-severe
asthma aged ≥12 years who have an eosinophilic phenotype or OCS–dependent asthma
§ A biologic targeting TSLP is in late-stage clinical development
64
QoL, quality of life.POST-TEST QUESTIONS 65
Post-test ARS Question 1 Post-AS1: How often WILL YOU (or someone in your office) NOW evaluate asthma symptom control using a validated questionnaire such as the Asthma Control Test or Asthma Apgar? 1. At every patient visit 2. At 75% of patient visits 3. At 50% of patient visits 4. At 25% of patient visits 5. Never 6. I do not treat patients with asthma 66
Post-test ARS Question 2 Post-AS2: How many of your patients with asthma WILL NOW have a written asthma action plan that you discuss at most of their appointments? 1. All of my patients with asthma 2. 75% of my patients 3. 50% of my patients 4. 25% of my patients 5. None of my patients 6. I do not treat patients with asthma 67
Post-test ARS Question 3 Post-AS3: A 37-year-old man has had 2 asthma exacerbations in the last 8 months despite using a high-dose inhaled corticosteroid and a long- acting β2-angonist daily. You refer this patient to a local asthma specialist. Which of the following tests will your colleague most likely order to determine if a biologic therapy targeting the IL-5 signaling pathway is appropriate for this patient? 1. Exhaled nitric oxide 2. Periostin level 3. Blood eosinophil count 4. High-resolution computed tomography of the chest 68
Post-test ARS Question 4 Post-AS4: Which of the following groups of biologic therapy FDA- approved for severe asthma has been designed to block signaling by interleukin (IL)-5? 1. Benralizumab, dupilumab, reslizumab 2. Benralizumab, mepolizumab, reslizumab 3. Dupilumab, mepolizumab, reslizumab 4. Mepolizumab, omalizumab, reslizumab 69
Post-test ARS Question 5 Post-AS5: According to the GINA recommendations, patients who require at least ______ course(s) of OCS within a year to control their asthma symptoms should be referred to an asthma specialist for evaluation. 1. 1 2. 2 3. 3 4. 4 70
Post-test ARS Question 6 Post-AS6: On average, how many patients with asthma do you manage each week? 1. None 2. 1-5 3. 6-15 4. 16-20 5. >20 71
Q&A 72
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