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nonresponders in the magnitude of
reduction in blood eosinophils.
Reslizumab is USFDA approved for
add-on therapy in adults aged 18 and
older with eosinophilic asthma.
Benralizumab
An RDBPCT of 369 adults with severe
asthma requiring oral steroid therapy
use noted that benralizumab use of 30
mg SC either every 4 weeks or every
8 weeks reduced median final oral
glucocorticoid dose from baseline by
75%, compared with a 25% reduction
in the placebo group. Benralizumab
use reduced the annual exacerbation
rate by 55% versus placebo when
administered every 4 weeks and by 70%
when administered every 8 weeks. No
significant effect on forced respiratory
volume 1 (FEV1) was noted.
Increased blood eosinophil levels
of more than 300 cells/µL have
been identified in some studies as a
biomarker of benralizumab efficacy.
However, a pooled analysis of SIROCCO
and CALIMA study data supported the
use of benralizumab in patients with
blood eosinophil counts =150 cells/
µL73 and a newly released subsequent
pooled analyses extended the efficacy
irrespective of eosinophil count,
although noting that the higher the
eosinophil count the greater the benefit.
Benralizumab is FDA approved
for patients with severe asthma aged
12 years and above, who have an
eosinophilic phenotype.
Dupilumab
Dupilumab is a human monoclonal
antibody to the alpha subunit of the IL4
receptor, thereby blocking the activity of
IL4 and IL13. Dupilumab is the only drug
approved for self-administration.
The IL4 cytokine is an essential
cytokine to T helper 2 (Th2) cell
polarization, whereas the IL13 cytokine
is associated with periostin production
in the bronchial epithelial cells,
ultimately resulting in smooth muscle
contraction, mucous production, airway
remodeling and hyper-responsiveness.
IL13 also works with IL4 to result in IgE
production.
An RDBPCT of dupilumab use in
104 adults aged between 18 and 65
years with moderate-to-severe
asthma and high blood or sputum
eosinophil counts above 300 cells/
µL and 3% respectively on mediumto-high
dose ICS plus LABAs resulted
in an 87% reduction in asthma
exacerbations and increased time to
asthma exacerbation despite stopping
LABA and ICS therapy while on
dupilumab compared with placebo.
There was noted improvement in
FEV1 as early as the second week
of treatment, which was maintained
for the 12 weeks of the study. An
RDBPCT of dupilumab using 300mg
SC every 2 weeks for 24 weeks in 210
adults with OCS-dependent asthma
noted a 59% decrease in severe
exacerbations in the dupilumab group
despite a -70.1% reduction in OCS.
An RDBPCT of 1902 adolescents
and adults with uncontrolled asthma
noted that dupilumab reduced severe
exacerbations by 47.7% compared
with placebo while increasing FEV1.
Dupilumab has been shown to
reduce FeNO levels and other levels
of Th2 inflammation including TARC,
eotaxin-3, and IgE.
Dupilumab has been approved by
US FDA for adolescents and adults aged
12 years and older with moderate-to-
are found to be critically involved in the inflammatory process
in the airways that results in the loss of lung function in
asthma. Several products have been developed to inhibit
the production, the function, and the survival of eosinophils.
These antibodies seem to work particularly well in individuals
with high eosinophil counts prior to treatment and who
have not responded to current treatment with inhaled
corticosteroids. Collectively, these products are well tolerated
and are effective in reducing eosinophil numbers and
preventing asthma exacerbations.
Multiple antibodies seek to tackle cytokines, which are
key in fuelling allergic-type responses and inflammation. But
the therapeutic agents that single out individual cytokines
for targeting proved to be largely ineffective due to the
overlapping effects of cellular signalling proteins. However,
antibodies blocking the effect of more than one cytokine have
shown promise.
Mepolizumab, reslizumab, and benralizumab are targeted
towards IL5, a cytokine that promotes both the activation and
longevity of eosinophils. Dupilumab is an anti-IL4 cytokine
antibody which is essential for Th2 cell polarization. Whereas,
biologic tralokinumab, that targets IL13 cytokine, is currently
under phase 2 development. IL13 is associated with periostin
production in the bronchial epithelial cells, ultimately resulting
in smooth muscle contraction, mucous production, airway
remodelling and hyper-responsiveness.
Today, clinicians have more than 10 years of clinical
experience with IgE targeting omalizumab and extensive trial
data with anti-eosinophil antibody mepolizumab. Unlike for
most drugs, outcomes in clinics with omalizumab have often
20 / FUTURE MEDICINE / May 2019