Advances in Managing Severe Asthma

Advances in The Management of
Severe Asthma
6/22/2019 1
Dr. Waseem Siddiqui

2
• Introduction
• Etiology
• Pathophysiology
• Clinical manifestation
• Classification
• Terminologies
• Severe Asthma
• GINA Guidelines for Severe Asthma Management
• Approved Monoclonal antibodies
• Landmark Clincal Studies of Approved MAb
Content

Bronchial Asthma-Introduction
Asthma is chronic inflammatory disease involving the airways affecting both children and adults
Definition: Asthma is a chronic inflammatory disease of the
airways that causes recurring episodes of wheezing,
breathlessness, chest tightness and coughing, particularly at
night or in the early morning. (European lung white book)
• Most commonly develops in early childhood, more than
three-quarters of children who develop asthma symptoms
before age 7 .
• However, asthma can develop at any stage in life, including
adulthood.
• Asthma has no cure. With today's knowledge and
treatments, most people who have asthma are able to
manage the disease.
• Deaths due to asthma are uncommon but are of serious
concern because many of them are preventabl
Facts & figures:
• Worldwide 339 million people have asthma1
• The global prevalence of Asthma is 4.3%2
• 26 million are diagnosed with asthma every year1
• Prevalence of Asthma is higher in developed
countries compared to developing countries
• 14% of the world’s children experience asthma
symptoms.1
• 8.6% of young adults (aged 18-45) experience
asthma symptoms.
• Burden of asthma - greatest for children aged 10-
14 and the elderly aged 75-79.
• Prevalence of severe uncontrolled asthma is 5-
10%3
1.The global Asthma report, 2018, http://www.globalasthmareport.org; 2. Lancet 2018; 391: 783–800; 3.Allergy Clin Immunol 2007; 119:4053

4
The prevalence of asthma varies widely around the world, probably because of
gene-by-environment interactions.
Susceptibility genes are thought to
include those for T-helper cells types
1 and 2 (TH1 and TH2), IgE,
interleukins (IL-3, -4, -5, -9, -13),
granulocyte-monocyte colony-
stimulating factor (GM-CSF), tumor
necrosis factor-α (TNF-α), and
the ADAM33 gene, which may
stimulate airway smooth muscle and
fibroblast proliferation or regulate
cytokine production.
Ex.ORMDL3
Allergen exposure, Diet,
Allergies, Indoor and
outdoor pollution
Asthma
RISK FACTORS
• Prenatal risk factors for asthma may
include maternal smoking, diet and
nutrition, stress, use of antibiotics and
delivery by cesarean section.
• Childhood risk factors- allergic
sensitization, environmental tobacco
smoke, exposure to animals,
breastfeeding, decreased lung function
in infancy, family size and structure,
socio-economic status, antibiotics and
infections, and sex and gender.
• Occupational exposures constitute a
common risk factor for adult asthma
TRIGGERS
• Allergens or irritants
• Exercise
• Medications or foods
• Viral or sinus infections
• Reflux disease
• Emotional anxiety
Bronchial Asthma- Etiology
It occurs as an interaction between body, environment and genetics
Wien Klin Wochenschr. 2016; 128(15): 541–554

Bronchial Asthma- TH2 Pathogenesis
TH2 cells activation and production of cytokines is the classical pathway for asthma. The non-eosinophilic pathway
of asthma involves activation of airway epithelial cells and macrophages by TLR4 and CD14
The mediators and cytokines released during the early phase of an
immune response to an inciting allergen, trigger a further inflammatory
response (late-phase asthmatic response) that leads to further airway
inflammation and bronchial hyper reactivity
Bronchospasm (contraction of the smooth muscle in the airways),
edema (swelling) and increased mucous secretion (mucous
hypersecretion), which lead to the characteristic SYMPTOMS OF
ASTHMA
Inflammatory mediators
Release of inflammatory mediators, such as histamine and cysteinyl
leukotrienes, PG’s , tryptase etc
Ig E production
Elevated levels of Th2 cells in the airways release specific cytokines, including
interleukin (IL)-4, IL-5, IL-9 and IL-13, that promote eosinophilic inflammation and
immunoglobulin E (IgE) production by mast cells
Immune mediated reactions
Various allergic and triggers produce a cascade of immune-mediated
events leading to chronic airway inflammation.
EMJ. 2018;3(4):111-121
J Allergy Clin Immunol Pract 2017;5:S1-S145

Bronchial Asthma- Progression of Disease
Change in tissue consequently causing bronchoconstriction, air-way edema, airway hyper-responsiveness & airway
re-modelling
EMJ. 2018;3(4):111-121
Broncho-
chonstrictio
n
•Allergen-induced acute bronchoconstriction results from an IgE-dependent release of
mediators from mast cells that includes histamine, tryptase, leukotrienes, and
prostaglandins that directly contract airway smooth muscle
•Aspirin and other nonsteroidal anti-inflammatory drugs can also cause acute airflow
obstruction in some patients
•Other stimuli (including exercise, cold air, and irritants) -acute airflow obstruction
Airway
edema
•Disease becomes more persistent inflammation more progressive,
•other factors further limit airflow
•Oedema, inflammation, mucus hypersecretion and the formation of inspissated mucus
plugs, as well as structural changes including hypertrophy and hyperplasia of the airway
smooth muscle.
•May not respond to usual treatment.
Airway hyper
responsivene
ss
•Exaggerated bronchoconstrictor response to a wide variety of stimuli—is a major, but not
necessarily unique.
•The degree to which airway hyperresponsiveness can be defined by contractile responses
to challenges with methacholine correlates with the clinical severity of asthma.
•Mechanisms influencing airway -multiple -inflammation, dysfunctional neuroregulation,
and structural changes
•Inflammation - major factor in determining the degree of airway hyperresponsiveness.
•Treatment directed toward reducing inflammation can reduce airway
hyperresponsiveness and improve asthma control.
Airway re-
modelling
•Some persons who have asthma, airflow limitation may be only partially reversible.
•Permanent structural changes can occur in the airway
•Progressive loss of lung function that is not prevented by or fully reversible by current therapy.
•Airway remodeling involves an activation of many of the structural cells, with consequent
permanent changes in the airway that increase airflow obstruction
•Patient less responsive to therapy
6

Bronchial Asthma- Clinical Manifestation
The symptoms of asthma are non-specific, characterised by wheezing, chest tightness, coughing and shortness of breathe
Wheeze
Breathe with a whistling or
rattling sound in the chest,
as a result of obstruction in
the air passages
Chest tightness
Cough
Shortness of breathe
Other symptoms include
• Hypoxia
• Nasal flaring
• Sputum is thick and tenacious
• Sometimes, decreased or absent
breathe sounds called “SILENT
CHEST”
• Symptoms are often worse at night
or on waking from sleep.
• Usually, they resolve spontaneously
or with the inhalation of a reliever
medication.
• May worsen over hours or minutes,
leading to more severe airflow
obstruction and an ‘attack’ or
exacerbation of asthma that is
relieved only by extra medication.
• Some very severe episodes are life-
threatening.
• Early warning signs &
symptoms
• Frequent cough, especially at
night
• Shortness of breath
• Feeling very tired or weak
when exercising
• Wheezing or
coughing after exercise
• Feeling tired, easily upset,
grouchy, or moody
• Decreases or changes in lung
function as measured on
a peak flow meter
• Signs of a cold
or allergies (sneezing, runny
nose, cough, nasal
congestion, sore throat,
and headache)
• Trouble sleeping
Lancet 2018; 391: 783–800
7

Bronchial Asthma- Classification
Asthma can be classified into Allergic, Eosinophilic & non-eosinophilic on basic of phenotypes with blood biomarkers
Curr Opin Pulm Med. 2017 May;23(3):254-260
Clinical and Molecular Phenotypes
• Early-onset allergic
• Late-onset eosinophilic
• Exercise induced
• Obesity-related
• Neutrophilic
Molecular Classification
• Th2 high (corticosteroid responsive)
• Th2 low (corticosteroids unresponsive)
Earlier Classification
• Allergic
• Non-allergic
8

Bronchial Asthma- Important Terminologies
Uncontrolled, Severe and Difficult to Treat Asthma are commonly used terminologies in the management o Asthma
Uncontrolled asthma
• Frequent symptoms and/or flare-ups (exacerbations)
• Many of these patients may potentially have mild asthma, i.e. their asthma could be well-controlled
with low dose ICS, if taken regularly
Difficult-to-treat asthma
• (not difficult patients!)
• Asthma uncontrolled despite prescribing high dose preventer treatment
• Contributory factors may include incorrect diagnosis, incorrect inhaler technique, poor adherence,
comorbidities
Severe asthma
• “Severe asthma” has had many different meanings
• Asthma that is uncontrolled despite maximal optimised therapy and treatment of contributory factors,
or that worsens when high dose treatment is decreased
• Relatively refractory to corticosteroids (rarely completely refractory)
GINA Pocket Guide Difficult to treat and severe asthma in adults and adolescents. GINA 2019. www.ginasthma.org
Med J Aust 2018; 209 (2): S3-S10
9

Bronchial Asthma- Important Terminologies
Phenotype, Endotype & Biomarkers are commonly used terminologies in the management o Asthma
Phenotype
The observable characteristics of a disease, such as morphology, development, biochemical or physiological properties, or
behaviour.
• Patients with an identified phenotype of obstructive lung disease may share a cluster of clinical, functional and/or
inflammatory features, without any implication of a common underlying mechanism
• Examples: allergic asthma, aspirin-exacerbated respiratory disease, severe eosinophilic asthma
Endotype:
A subtype of disease, defined functionally and pathologically by a distinct molecular mechanism or by distinct treatment
responses (Anderson, Lancet 2008)
• Among patients with obstructive lung disease, there are likely to be several specific endotypes associated with divergent
underlying molecular causes, and with distinct treatment responses. These endotypes may or may not align with clinical or
inflammatory phenotypes identified from studies limited to asthma or to COPD
• Examples: emphysema due to alpha1-antitrypsin deficiency
Biomarker
A defined characteristic measured as an indicator of normal biologic processes, pathogenic processes or response to an
intervention
• Potential examples: FeNO, blood eosinophils, sputum eosiniphils– but these may not meet quality criteria for biomarkers
10

Bronchial Asthma- How Common is Severe Asthma?
A Dutch population survey of people >18 years shows that 3.7% people were affected by severe asthma
Hekking et al, JACI 2015
11

Bronchial Asthma- How to Evaluate Severe Asthma?
Evaluation of difficult-to-treat asthma vs severe asthma
Med J Aust 2018; 209 (2): S3-S10
12

* Off-label; data only with budesonide-formoterol (bud-form)
† Off-label; separate or combination ICS and SABA inhalers
STEP 2
Daily low dose inhaled corticosteroid (ICS),
or as-needed low dose ICS-formoterol *
STEP 3
Low dose
ICS-LABA
STEP 4
Medium dose
ICS-LABA
Leukotriene receptor antagonist (LTRA), or
low dose ICS taken whenever SABA taken †
As-needed low dose ICS-formoterol *
As-needed short-acting β2 -agonist (SABA)
Medium dose
ICS, or low dose
ICS+LTRA #
High dose
ICS, add-on
tiotropium, or
add-on LTRA #
Add low dose
OCS, but
consider
side-effects
As-needed low dose ICS-formoterol ‡
STEP 5
High dose
ICS-LABA
Refer for
phenotypic
assessment
± add-on
therapy,
e.g.tiotropium,
anti-IgE,
anti-IL5/5R,
anti-IL4R
Symptoms
Exacerbations
Side-effects
Lung function
Patient satisfaction
Confirmation of diagnosis if necessary
Symptom control & modifiable
risk factors (including lung function)
Comorbidities
Inhaler technique & adherence
Patient goals
Treatment of modifiable risk
factors & comorbidities
Non-pharmacological strategies
Education & skills training
Asthma medications
1
STEP 1
As-needed
low dose
ICS-formoterol *
Low dose ICS
taken whenever
SABA is taken†
‡ Low-dose ICS-form is the reliever for patients prescribed
bud-form or BDP-form maintenance and reliever therapy
# Consider adding HDM SLIT for sensitized patients with
allergic rhinitis and FEV >70% predicted
PREFERRED
CONTROLLER
to prevent exacerbations
and control symptoms
Other
controller options
Other
reliever option
PREFERRED
RELIEVER
Personalized asthma management:
Assess, Adjust, Review response
Asthma medication options:
Adjust treatment up and down for
individual patient needs
SEVERE ASTHMA AS PER
GINA 2019
Bronchial Asthma- Management of Severe Asthma
Evaluation of severe asthma as per GINA 2019 guidelines
6/22/2019 13

Bronchial Asthma- Management of Difficult to Treat & Severe Asthma
6/22/2019 14

6/22/2019 15

6/22/2019 16

6/22/2019 17

6/22/2019 18

6/22/2019 19

6/22/2019 20

6/22/2019 21

6/22/2019 22

6/22/2019 23

6/22/2019 24

6/22/2019 25

6/22/2019 26

6/22/2019 27

6/22/2019 28

6/22/2019 29

6/22/2019 30

Bronchial Asthma- Characteristic of Approved Monoclonal Antibodies
Five monoclonal antibodies are approved by the USFDA for the management of severe asthma
Drug MOA Indication Dose Adverse Effects Evidence
Omalizumab
(Novartis,
2003)
Anti- IgE
Mab
Moderate–severe persistent asthma
uncontrolled by ICS in ages 6 years
positive for perennial aeroallergens
75-375 mg, SC,
Q 2-4weeks
(dose is weight
dependent)
BBW: anaphylaxis
10%: injection site reaction
0.5%: malignancies
1%-10%:cv, dermatologic,
neuromuscular effects
Reduced all exacerbations
by 25% and severe
exacerbations by 50%
Mepolizumab
(GSK, 2015)
IL-5
antibody
(IgG1
kappa)
Add-on maintenance treatment for
severe asthma in ages >12 years with
eosinophilic phenotype
100mg, SC, Q4
weeks
5%: headache, injection site
reaction, back pain, fatigue
3%: pruritus, eczema, muscle
spasms, abdominal pain
>50% reduction in overall
exacerbation rate and a
>60% reduction in hosp.
/ED visits
Reslizumab
(Teva, 2016)
IL-5
antibody
(IgG4
kappa)
severe asthma in adults with
3mg/kg, IV
infusion, Q4
weeks
BBW: anaphylaxis
5%: antibody development
3%: oropharyngeal pain
>50% improvement in
quality of life and an FEV1
improvement by 90–160
mL
Benralizumab
(AZ, 2017)
IL-5a RA,
adcc
severe, asthma in >12 years
with an eosinophilic phenotype
30mg, SC, 0, 4,
8 weeks f/b Q8
weeks
Headache, pharyngitis,
injection-site reactions
>50% reduction in
exacerbations and a lung
function improvement of
24%.
Dupilumab
(Sanofi &
Regeneron,
2018)
IL-13/IL-4
Mab
moderate-to-severe asthma in >12
years with eosinophilic phenotype or
with corticosteroid dependent
asthma
400/ 600 mg
SC loading
dose f/b
300mg SC
alternate week
10%: injection site reactions,
conjunctivitis
Improved severe
exacerbation rates by
>47% and an improved
FEV1 by 320 mL
Tezepelumab
(Phase III)
TSLP MAb Poor control on ICS/LABA, >2
exacerbations per year.
70 mg vs 210
mg 4 weekly or
280 mg 2
weekly
Injection site reaction Exacerbation lowered by
>60% and FEV1 improved
by >110 mL in all groups
M-Ab, monoclonal antibodies; IL, interleukin; ICS inhaled corticosteroid; BBW, black-box warning; SC, sub-cutaneous, adct, antibody dependent cell medicated
cyto-toxicity; RA, receptor antagonist; f/b, followed by;
Koski RR, et al. J Pharm Pract. 2019; EMJ. 2018;3(4):111-121
31

Bronchial Asthma- Characteristic of Approved Monoclonal Antibodies
MOA of Mab approved for asthma and those under development
J Allergy Clin Immunol Pract. 2017 Mar - Apr;5(2S):S1-S1432

Bronchial Asthma- Landmark Studies of Omalizumab
Omalizumab is anti-IgE Mab, approved since 2003 for the management of severe persistent asthma
M-Ab, monoclonal antibodies; IL, interleukin; ICS inhaled corticosteroid; SQ, sub-cutaneous: RA, receptor antagonist; f/b, followed by;
Study N
Age
(years) Inclusion Criteria Treatment
Primary Efficacy
End Point Results
Busse et al1 525 12-75
Allergic asthmatics
with symptoms
despite ICS use, total
serum IgE 30- 700
IU/mL
150 mg, 300 mg, or
placebo SQ Q4
weeks Or 225 mg,
300 mg, 375 mg, or
placebo Q2
weeks*28 weeks
Number of patients
with exacerbations
during steroid stable
phase and steroid
reducing phase
Less patients with asthma exacerbations
during steroid-stable (RR reduction by
55%); significantly less number and
duration of exacerbations, symptoms,
rescue inhaler use, and ICS dose with
omalizumab vs placebo
Adverse event profile similar to placebo
Humbert et
al2 419 12-75
Uncontrolled severe
persistent asthma on
high-dose ICS and
LABA, total serum IgE
30-700 IU/ mL
SQ dose determined
by body weight and
baseline total serum
IgE or placebo Q2-4
weeks*28 weeks
Rate of clinically
significant asthma
exacerbations
Decreased exacerbation rate (RR
reduction by 52%). significantly greater
reduction in emergency room visits and
symptoms and improved FEV1 with
omalizumab vs placebo
1.Allergy Clin Immunol. 2001;108(2):184-190.
2.Allergy. 2005;60:309-316.
33

Bronchial Asthma- Landmark Studies of Mepolizumab
Mepolizumab is anti- IL5 Mab, approved since 2015 for management of severe asthma in eosinophilic phenotype
M-Ab, monoclonal antibodies; IL, interleukin; ICS inhaled corticosteroid; SQ, sub-cutaneous: RA, receptor antagonist; f/b, followed by; ACQ, Asthma control
questionnaire; SGRQ, St George’s respiratory questionnaire; AQLQ, Asthma quality of life questionnaire
1.N Engl J Med. 2014;371(13):1189-1197.
2.N Engl J Med. 2014; 371(13):1198-1207
Study Duration, n Patients Primary Outcome Secondary Outcome
Bel et al1
2014;
SIRIUS
phase 3
20 weeks,
n=135
Age range 16–74 years; background therapy (5–35
mg/day of prednisone or equivalent) for >6 months;
blood eosinophil count ≥150 cells/μL at screening or
≥300 cells per μL in the previous year
Oral corticosteroid use:
significant decrease in
oral corticosteroid use
(by about 50%)
Significant decrease in
exacerbation rate by
around 32%; significant
decrease in ACQ (by
about 0·52)
Ortega et
al
2014;
MENSA
phase 3
32 weeks,
n=576
Adults and children (aged ≥12 years); background
therapy (≥880 μg/day fluticasone propionate or
equivalent) for >3 months and an additional
controller; ≥2 exacerbations in the previous year;
blood eosinophil count ≥150 cells per μL at screening
or ≥300 cells per μL in the last year
Exacerbation rate:
exacerbation rate by
around 50%
Significant increase in
FEV1 (by 100 mL);
ACQ (by around 0·43);
SGRQ (by around 7)
34

Bronchial Asthma- Landmark Studies of Reslizumab
1.Lancet Respir Med. 2015;3(5):355-366.
2. Chest. 2016;150(4):799-810
Study Duration, n Patients Primary Outcome Secondary Outcome
Castro et al
20151;
phase 3
52 weeks,
n=953
(study 1
n=489, study 2
n=464)
Adults and children (12–75 years); bronchodilator
response >12%; ACQ ≥1·5; background therapy (≥440
μg/day fluticasone propionate or equivalent) for >1
month and an additional controller; ≥1 exacerbation
in last year; blood eosinophil count ≥400 cells per μL
Exacerbation rate
(eosinophil high only
recruited >400 cells per
μL) significant decrease
in exacerbation rate by
60–80%
FEV1 (by 100 mL);
ACQ (by about 0·25);
significant increase in
AQLQ (by about 0·23)
Corren et
al 2016
16 weeks,
n=492
Adults and children (12–65 years); bronchodilator
response >12%; background therapy (≥440 μg/day
fluticasone propionate or equivalent) for >1 month
and an additional controller; ACQ ≥1·5
FEV1 at week 16 non-
significant change
Eosinophil high: significant
increase in FEV1 (by 270
mL); significant decrease
in ACQ (by 0·49); no
benefits in eosinophil low
group
Reslizumab is anti- IL5 Mab, approved since 2016 for management of severe asthma in eosinophilic phenotype
35

Bronchial Asthma- Landmark Studies of Benralizumab
Benralizumab is IL-5α RA, approved by the USFDA in 2017 for the management of severe asthma with an
1. Lancet Respir Med. 2016; 388:2115-2127
2. Lancet Respir Med. 2016;388:2128-2141
Study
Duration,
n Patients Primary Outcome Secondary Outcome
Bleecker
et al1
2016;
SIROCCO
phase 3
48 weeks,
n=1205
Adults and children (12–75 years); prebronchodilator
FEV1 <80% (adults), <90% (children); bronchodilator
response >12%; background therapy ICS plus LABA for ≥1
year before enrolment (high-dose ICS in adults and
moderate-to-high in children) and another controller; ≥2
exacerbations in the previous year; ACQ ≥1·5
Exacerbation rate in
eosinophil high:
exacerbation rate (by
around 50%)
FEV1 (by 110 mL);
ACQ (by about 0·25);
AQLQ (by around 0·25)
FitzGerald
et al2
2016;
CALIMA
phase 3
56 weeks,
n=306
Adults and children (12–75 years); prebronchodilator
FEV1 <80% (adults), <90% (children); bronchodilator
response >12%; background therapy ICS plus LABA for ≥1
year before enrolment (high-dose ICS in adults and
moderate-to-high in children) and another controller; ≥2
exacerbations in the previous year; ACQ ≥1·5
Exacerbation rate in
eosinophil high:
exacerbation rate (by
around 30%)
FEV1 (by about 120 mL);
ACQ (by around 0·2);
AQLQ (by 0·2)
36

Bronchial Asthma- Landmark Studies of Dupilumab
Duplilumab is approved by the USFDA in 2018 for the management of moderate- severe asthma with
1.Lancet. 2016;388:31-44
2.N Engl J Med. 2018;378:2486-2496
Study N
Age
(year
s)
Inclusion
Criteria Treatment
Primary Efficacy End
Point Results
Wenzel
et al1 769>18
Asthma on
medium-high
dose ICS and
long-acting
beta-agonist
400 mg SQ LD f/b 200
mg SQ Q2 or 4 weeks,
mg SQ Q2 or 4 weeks,
or placebo 24 weeks
Change from aseline in
prebronchodilator FEV1 at
week 12 for those with
eosinophil count 300 cells/mL
Significantly greater improvement in FEV1
with dupilumab vs placebo, benefit if
eosinophil count <300 cells/mL for every 2
weeks doses; increased eosinophil count
with dupilumab vs placebo
Castro et
al2
(Liberty
Asthma
QUEST) 1902>12
Asthma on
medium-high
dose ICS +2
other
controllers
mg SQ Q2 weeks, 600
mg SQ LD f/b 300 mg
SQ Q2 weeks, or
placebo 52 weeks
Annual rate of severe
exacerbations, change from
baseline in FEV1 at week 12
Less annual severe exacerbations with 200
mg and 300 mg dupilumab vs placebo (P <
.001), more benefit if eosinophil count >300
cells/mL; higher FEV1 with dupilumab vs
placebo (P < .001); increased eosinophil
count with dupilumab v placebo
37

Bronchial Asthma- Future Target for Management
There are multiple new target for the management of asthma are under various phase of development
• Tezepelumab: targeting TSLP (thymic stromal lymphopoietin), received USFDA breakthrough
status on the basis of phase 2b results. It’s action is independent of Th2 high or low pathway as
it TSLP is an upstream regulator of multiple inflammatory pathway. Currently under phase III of
development.
• Tralokinumab: targeting IL- 13. Currently under phase III of development
• Lebrikizumab: targeting IL- 13. Currently under phase III of development
• Fevipiprant: prostaglandin D2 receptor antagonist. Currently under phase III of development
• Bronchial Thermoplasty: It is a novel, FDA approved interventional procedure that reduces
airway smooth muscle via the application of targeted thermal energy at 65 C to the airways
Curr Opin Pulm Med. 2017 May;23(3):254-260
38

Is Precision Medicine Future of Bronchial Asthma Management?
Management of asthma on the basis of patients profile by using genetics or molecular profiling

Is Precision Medicine Future of Bronchial Asthma Management?
Management of asthma on the basis of patients profile by using genetics or molecular profiling
Tezepelumab Adalimumab, Infliximab,
Golimumab,
Secukinumab
Allergy, First published: 13 March 2019, DOI: (10.1111/all.13771)
40

Bronchial Asthma- Opportunities & Challenges
There are multiple new target based therapies have come but still there are multiple challenges in asthma
management
• What biomarkers to be used to predict optimal response in type 2-high asthma patients on
targeted biologics
• Whether newer target will provide better control of asthma?
• Biomarkers for type 2–low asthma
• Biologics that induce true immunomodulation: prevent/alter disease course
• Are epithelial alarmins (TSLP, IL25 & IL33) the best option for both (type 2- low and type 2-high
asthma management)?
• Whether other anti IgE mAb will provide the better control than omalizumab?
• Phenotype/endotype (biomarker)–driven, biologic-specific therapies (precise patient therapy)
• Inexpensive and easily obtainable point-of-care biomarkers
• Biologics with favorable risk/benefit ratio
• Biologics with convenient dosing
• Affordable/cost-effective biologics
41

Advances in Managing Severe Asthma

Recommended

Recommended

More Related Content

What's hot

What's hot (20)

Similar to Advances in Managing Severe Asthma

Similar to Advances in Managing Severe Asthma (20)

Recently uploaded

Recently uploaded (20)

Advances in Managing Severe Asthma