Page 119 - Škrgat, Sabina, ed. 2022. Severe Asthma - Basic and Clinical Views. Koper: University of Primorska Press. Severe Asthma Forum, 1
P. 119
61%. It also improves the quality of life β-agonists, with baseline blood eosinophil 119
and lung function, which is reflected in the av- counts ≥300 cells/μL.
erage increase in FEV1 compared to placebo eosinophilic and allergic asthma phenotype and therapeutic possibilities
(P=0.03).33,34,38 Dupilumab is the only biologic that has
dual inhibitory activity; inhibits the signa-
Reslizumab is also a humanized mono- ling pathways of IL-4 and IL-13 by block-
clonal IgG4 antibody, administered intrave- ing the alpha chain of the IL-4 receptor,
nously at a dose of 3 mg/kg body weight every thus acting on two separate pathophysiolog-
four weeks. Reslizumab is indicated in pa- ical pathways cause eosinophilic inflamma-
tients with uncontrolled severe asthma despite tion in asthma:allergic and non-alergic eosin-
treatment with high doses of inhaled corticos- ophilic patways. So, effects are not limited to
teroids with a long-acting beta2-agonist, with those patients who have eosinophilia28. Dup-
the addition of one or more controllers and/ ilumab improved lung function and reduced
or with additional OCS therapy. The blood severe exacerbations in patients with an un-
eosinophil counts of ≥150 cells/μL at screen- controlled severe asthma, regardless of the in-
ing or ≥ 300 cells/μL within 12 months pri- itial number of eosinophils and had a favora-
or to treatment of ≥300 cells/μl i had to be ble safety profile, and therefore with inhaled
present. Reslizumab reduces the incidence of corticosteroids and long-term therapy with
asthma exacerbations compared to those re- β2-agonists could improve the life of patients
ceiving placebo, In two studies of Castro et with uncontrolled asthma in standard treat-
al, patients receiving reslizumab had a signifi- ment.34,41,42 Therefore, dupilumab is indicated
cant reduction in the frequency of asthma ex- in adults and adolescents 12 years and older
acerbations - in study 1. exacerbation rate was with severe asthma characterised by blood eo-
reduced by 50%; in study 2 exacerbation rate sinophil count of >150 cells/µL and/or raised
reduced by 59%; both p<0·0001) compared fraction of exhaled nitric oxide (FeNO) >25
with those receiving placebo. Lung function ppb, inadequately controlled with high dose
(FEV1) , asthma control (ACQ ) and quality ICS and one of more controlers.
of life (AQLQ ) have been improved over pla-
cebo.32-34,39 Looking into the Near Future:
Anti-epithelial Cytokine Antibodies
Benralizumab has a dual effect: it is a
blocker of the IL-5Rα receptor on the eosin- The epithelial cytokines: thymic stromal lym-
ophil membrane and thus prevents the bind- phopoietin (TSLP), IL-25 and IL-33 are re-
ing of activated IL-5, while binding NK cells leased from the airway epithelium in response
that cause accelerated eosinophil apoptosis. to allergens, air pollution, and viruses trig-
This effect is associated with a rapid reduc- gering an inflammatory cascade in asthma.
tion in eosinophilia in the blood. It is adminis- It has been hypothesized that the blockade
tered subcutaneously at a dose of 30 mg every of these cytokines, compared with biological
four weeks for the first three doses and then agents aimed at T2-inflammation, could im-
every eight weeks. Benralizumab significant- prove severe asthma outcomes in a much wid-
ly reduced asthma exacerbations and conse- er patient population. The results of recent
quently progressively reduced daily OCS in- RCTs have shown the efficiency of tezepelum-
take, improved ACT questionnaire value and ab, a human monoclonal antibody which tar-
an increase in lung function.33,34,40. Benral- gets TSLP; itepekimab, an anti IL-33 human
izumab is indicated in patients 12 years or monoclonal antibody; and astegolimab, a hu-
older and in adults with severe eosinophilic man monoclonal antibody with an IL-33 re-
asthma inadequately controlled despite high- ceptor blockade effect in patients with severe
dose inhaled corticosteroids plus long-acting asthma.45-48
and lung function, which is reflected in the av- counts ≥300 cells/μL.
erage increase in FEV1 compared to placebo eosinophilic and allergic asthma phenotype and therapeutic possibilities
(P=0.03).33,34,38 Dupilumab is the only biologic that has
dual inhibitory activity; inhibits the signa-
Reslizumab is also a humanized mono- ling pathways of IL-4 and IL-13 by block-
clonal IgG4 antibody, administered intrave- ing the alpha chain of the IL-4 receptor,
nously at a dose of 3 mg/kg body weight every thus acting on two separate pathophysiolog-
four weeks. Reslizumab is indicated in pa- ical pathways cause eosinophilic inflamma-
tients with uncontrolled severe asthma despite tion in asthma:allergic and non-alergic eosin-
treatment with high doses of inhaled corticos- ophilic patways. So, effects are not limited to
teroids with a long-acting beta2-agonist, with those patients who have eosinophilia28. Dup-
the addition of one or more controllers and/ ilumab improved lung function and reduced
or with additional OCS therapy. The blood severe exacerbations in patients with an un-
eosinophil counts of ≥150 cells/μL at screen- controlled severe asthma, regardless of the in-
ing or ≥ 300 cells/μL within 12 months pri- itial number of eosinophils and had a favora-
or to treatment of ≥300 cells/μl i had to be ble safety profile, and therefore with inhaled
present. Reslizumab reduces the incidence of corticosteroids and long-term therapy with
asthma exacerbations compared to those re- β2-agonists could improve the life of patients
ceiving placebo, In two studies of Castro et with uncontrolled asthma in standard treat-
al, patients receiving reslizumab had a signifi- ment.34,41,42 Therefore, dupilumab is indicated
cant reduction in the frequency of asthma ex- in adults and adolescents 12 years and older
acerbations - in study 1. exacerbation rate was with severe asthma characterised by blood eo-
reduced by 50%; in study 2 exacerbation rate sinophil count of >150 cells/µL and/or raised
reduced by 59%; both p<0·0001) compared fraction of exhaled nitric oxide (FeNO) >25
with those receiving placebo. Lung function ppb, inadequately controlled with high dose
(FEV1) , asthma control (ACQ ) and quality ICS and one of more controlers.
of life (AQLQ ) have been improved over pla-
cebo.32-34,39 Looking into the Near Future:
Anti-epithelial Cytokine Antibodies
Benralizumab has a dual effect: it is a
blocker of the IL-5Rα receptor on the eosin- The epithelial cytokines: thymic stromal lym-
ophil membrane and thus prevents the bind- phopoietin (TSLP), IL-25 and IL-33 are re-
ing of activated IL-5, while binding NK cells leased from the airway epithelium in response
that cause accelerated eosinophil apoptosis. to allergens, air pollution, and viruses trig-
This effect is associated with a rapid reduc- gering an inflammatory cascade in asthma.
tion in eosinophilia in the blood. It is adminis- It has been hypothesized that the blockade
tered subcutaneously at a dose of 30 mg every of these cytokines, compared with biological
four weeks for the first three doses and then agents aimed at T2-inflammation, could im-
every eight weeks. Benralizumab significant- prove severe asthma outcomes in a much wid-
ly reduced asthma exacerbations and conse- er patient population. The results of recent
quently progressively reduced daily OCS in- RCTs have shown the efficiency of tezepelum-
take, improved ACT questionnaire value and ab, a human monoclonal antibody which tar-
an increase in lung function.33,34,40. Benral- gets TSLP; itepekimab, an anti IL-33 human
izumab is indicated in patients 12 years or monoclonal antibody; and astegolimab, a hu-
older and in adults with severe eosinophilic man monoclonal antibody with an IL-33 re-
asthma inadequately controlled despite high- ceptor blockade effect in patients with severe
dose inhaled corticosteroids plus long-acting asthma.45-48
