Page 118 - Škrgat, Sabina, ed. 2022. Severe Asthma - Basic and Clinical Views. Koper: University of Primorska Press. Severe Asthma Forum, 1
P. 118
sputum. In some patients, “aspirin exac- and higher blood eosinophils may benefit
erbated respiratory disease” is also pres- from delayed omalizumab therapy.33,36
severe asthma forum 1: severe asthma - basic and clinical views ent.21,28,29
Mechanism of Action of Anti IL-5/Anti IL-
While IgE is involved early in the inflam- 5Rα and Anti IL-4/IL-13 Treatments
matory cascade and can be considered a cause in Eosinophilic Asthma Phenotype
of allergic asthma, eosinophilia can be con-
sidered a consequence of the whole process. IL-5 is a key factor in the eosinophil matura-
Hence the different roles of the IgE pathway tion, mediates eosinophil mobilisation, acti-
and the IL-5 eosinophil pathway in the path- vation and survival. It achieves its effects by
ogenic mechanisms of airway inflammation binding to a specific subunit of the IL-5 re-
occurring in asthma, and thus the reason for ceptor, which is IL-5Rα. The IL-5Rα subu-
choosing anti-IgE monoclonal antibody or nit binds only IL-5. Eosinophils express up to
anti-IL-5/IL-5Rα treatment.30 three times more IL-5Rα on their cell mem-
brane than basophils. Th2 cells, mast cells,
Mechanisms of Action of Anti-IgE innate lymphoid cells (ILC 2), CD34 + pro-
Treatment in Allergic Asthma Phenotype genitor cells, natural killer (NK) T cells and
eosinophils themselves are the main cellular
Omalizumab is an anti-IgE treatment. It source of IL-537 Therefore, targeting IL-5 or
binds to free IgE and thus reduces the bind- IL-5Rα is a logical approach to treat patients
ing of IgE to mast cells, basophils and eosin- with severe eosinophilic asthma.
ophils. In addition, omalizumab reduces the
expression of high-affinity FcεRI receptors Two different anti-IL-5 monoclonal anti-
for IgE on these cells, thereby further reduc- bodies, mepolizumab and reslizumab, bind to
ing IgE binding to them. This reduces the different epitopes of IL-5 by interfering with
release of mediators from the cells, reduces its binding to IL-5R expressed on the eosino-
allergic inflammation, prevents the exacer- phil membrane by reducing the IL-5 signal-
bation of asthma and reduces symptoms.31,32 ing pathway that impairs eosinophil matura-
Omalizumab is indicated for adults and chil- tion and survival.
dren over six years of age with uncontrolled
moderate to severe allergic asthma with ele- Mepolizumab is a humanized monoclo-
vated total IgE antibodies, a positive skin al- nal IgG4 antibody, administered subcuta-
lergy test, or specific IgE antibodies to peren- neously at a dose of 100 mg every 4 weeks.
nial allergens.33A Criteria for introducing mepolizumab into
treatment are: forced expiratory volume in
Omalizumab statistically significantly 1 second (FEV1) less than 80% of predict-
reduced daily symptoms, reduced exacerba- ed value, at least two exacerbations of asth-
tions, and the dose of inhaled corticosteroids. ma in the previous year treated with systemic
Omalizumab has improved asthma control glucocorticoids while the patient was treat-
and reduced the need for other asthma med- ed with high doses of inhaled corticosteroids
ications. All these effects are visible after 12 with a long-acting beta2-agonist, and at least
weeks of therapy.32,34,35 In the STELLAIR with an additional controller and an eosino-
study, the rate of exacerbation reduction was phil count of at least 150 cells per microliter in
similar in patients with severe allergic asth- peripheral blood at screening or at least 300
ma with high (≥ 300 cells/µL) and low (< cells per microliter at some point during the
300 cells/µL) eosinophils. Patients with high- previous year. Mepolizumab reduces the rate
er serum IgE levels, shorter disease duration of exacerbations by 53% compared to place-
bo (P<0.001), reduces exacerbations requir-
ing an emergency visit and hospitalization
erbated respiratory disease” is also pres- from delayed omalizumab therapy.33,36
severe asthma forum 1: severe asthma - basic and clinical views ent.21,28,29
Mechanism of Action of Anti IL-5/Anti IL-
While IgE is involved early in the inflam- 5Rα and Anti IL-4/IL-13 Treatments
matory cascade and can be considered a cause in Eosinophilic Asthma Phenotype
of allergic asthma, eosinophilia can be con-
sidered a consequence of the whole process. IL-5 is a key factor in the eosinophil matura-
Hence the different roles of the IgE pathway tion, mediates eosinophil mobilisation, acti-
and the IL-5 eosinophil pathway in the path- vation and survival. It achieves its effects by
ogenic mechanisms of airway inflammation binding to a specific subunit of the IL-5 re-
occurring in asthma, and thus the reason for ceptor, which is IL-5Rα. The IL-5Rα subu-
choosing anti-IgE monoclonal antibody or nit binds only IL-5. Eosinophils express up to
anti-IL-5/IL-5Rα treatment.30 three times more IL-5Rα on their cell mem-
brane than basophils. Th2 cells, mast cells,
Mechanisms of Action of Anti-IgE innate lymphoid cells (ILC 2), CD34 + pro-
Treatment in Allergic Asthma Phenotype genitor cells, natural killer (NK) T cells and
eosinophils themselves are the main cellular
Omalizumab is an anti-IgE treatment. It source of IL-537 Therefore, targeting IL-5 or
binds to free IgE and thus reduces the bind- IL-5Rα is a logical approach to treat patients
ing of IgE to mast cells, basophils and eosin- with severe eosinophilic asthma.
ophils. In addition, omalizumab reduces the
expression of high-affinity FcεRI receptors Two different anti-IL-5 monoclonal anti-
for IgE on these cells, thereby further reduc- bodies, mepolizumab and reslizumab, bind to
ing IgE binding to them. This reduces the different epitopes of IL-5 by interfering with
release of mediators from the cells, reduces its binding to IL-5R expressed on the eosino-
allergic inflammation, prevents the exacer- phil membrane by reducing the IL-5 signal-
bation of asthma and reduces symptoms.31,32 ing pathway that impairs eosinophil matura-
Omalizumab is indicated for adults and chil- tion and survival.
dren over six years of age with uncontrolled
moderate to severe allergic asthma with ele- Mepolizumab is a humanized monoclo-
vated total IgE antibodies, a positive skin al- nal IgG4 antibody, administered subcuta-
lergy test, or specific IgE antibodies to peren- neously at a dose of 100 mg every 4 weeks.
nial allergens.33A Criteria for introducing mepolizumab into
treatment are: forced expiratory volume in
Omalizumab statistically significantly 1 second (FEV1) less than 80% of predict-
reduced daily symptoms, reduced exacerba- ed value, at least two exacerbations of asth-
tions, and the dose of inhaled corticosteroids. ma in the previous year treated with systemic
Omalizumab has improved asthma control glucocorticoids while the patient was treat-
and reduced the need for other asthma med- ed with high doses of inhaled corticosteroids
ications. All these effects are visible after 12 with a long-acting beta2-agonist, and at least
weeks of therapy.32,34,35 In the STELLAIR with an additional controller and an eosino-
study, the rate of exacerbation reduction was phil count of at least 150 cells per microliter in
similar in patients with severe allergic asth- peripheral blood at screening or at least 300
ma with high (≥ 300 cells/µL) and low (< cells per microliter at some point during the
300 cells/µL) eosinophils. Patients with high- previous year. Mepolizumab reduces the rate
er serum IgE levels, shorter disease duration of exacerbations by 53% compared to place-
bo (P<0.001), reduces exacerbations requir-
ing an emergency visit and hospitalization
