Table 2.

Approved biological therapies for severe asthma treatment: when, which, and for whom, in agreement with EMA and FDA documents

	Omalizumab	Mepolizumab	Reslizumab	Benralizumab	Dupilumab
Date of issue of marketing authorization and reference of product information	EMA 2005 [82] FDA 2003 [83]	EMA 2015 [35] FDA 2015 [34]	EMA 2016 [84] FDA 2016 [85]	EMA 2018 [86] FDA 2017 [87]	EMA 2019 [57] FDA 2017 [58]
Age of patients (when)	EMA: 6 years of age and older FDA: 6 years of age and older	EMA: 6 years of age and older FDA: 12 years of age and older	EMA: adult patients FDA: adult patients	EMA: adult patients FDA: 12 years of age and older	EMA: 12 years of age and older FDA: 12 years of age and older
mAB (which)	Humanized anti-IgE	Humanized anti-IL-5	Humanized anti-IL-5	Humanized anti-IL-5Rα	Humanized anti-IL-4Rα
Disease characteristics (for whom)	EMA: add-on treatment for IgE-mediated asthma with positive skin test or in vitro reactivity to a perennial aeroallergen, frequent daytime symptoms or night-time awakenings, multiple documented severe asthma exacerbations despite treatment with high doses of a ICS/LABA combination; reduced lung function (FEV1 < 80% predicted) in patients aged 12 years or over FDA: moderate to severe persistent asthma with a positive skin test or in vitro reactivity to a perennial aeroallergen and symptoms that are inadequately controlled with ICS	EMA: add-on treatment for severe refractory eosinophilic asthma FDA: add-on treatment for severe asthma with eosinophilic phenotype	EMA: add-on treatment for severe eosinophilic asthma inadequately controlled despite treatment with high-dose ICSs plus another medicinal product for maintenance treatment FDA: add-on treatment for severe eosinophilic asthma	EMA: add-on treatment for severe eosinophilic asthma inadequately controlled despite treatment with high-dose ICS/LABA combination FDA: add-on treatment for severe eosinophilic asthma	EMA: add-on treatment for type II severe asthma with increased blood eosinophils and/or raised exhaled nitric oxide inadequately controlled by high-dose ICSs plus another asthma medicinal product FDA: add-on treatment for moderate-to-severe eosinophilic asthma or oral corticosteroid-dependent asthma
Posology	75–600 mg in one to four subcutaneous injections every 4 weeks; the maximum recommended dose is 600 mg every 2 weeks	100 mg administered subcutaneously once every 4 weeks in adults and adolescents aged 12 years or over; 40 mg administered subcutaneously once every 4 weeks in children aged between 6 and 11 years	3 mg for each kg of bodyweight via intravenous infusion once every 4 weeks	30 mg by subcutaneous injection every 4 weeks for the first 3 doses, and then every 8 weeks thereafter	An initial dose of 400 mg (two 200 mg subcutaneous injections) followed by 200 mg given every other week; an initial dose of 600 mg (two 300 mg subcutaneous injections) followed by 300 mg given every other week; for patients requiring concomitant oral corticosteroids or with comorbid moderate-to-severe atopic dermatitis for which dupilumab is indicated, start with an initial dose of 600 mg followed by 300 mg given every other week
Main benefits	Adults and adolescents: ≈ 50% reduction in the number of exacerbations; improvement in quality of life and reduction in the use of ICS. Children: ≈ 20% reduction in the number of exacerbations. Data are reported vs. placebo	Adults and adolescents: ≈ 50% reduction in the number of exacerbations; about half of the patients reduced the daily dose of oral corticosteroid dose by more than 50% to a dose of 5 mg or less. Children: the reduction in eosinophil levels in the blood was comparable with that detected in adults. Data are reported vs. placebo	≈ 30% reduction in the number of exacerbations; improvement in lung function and asthma symptoms; decreased number of blood eosinophils. Data are reported vs. placebo	≈ 50% reduction in the number of exacerbations; ≈ 50% reduction in the daily oral corticosteroid dose. Data are reported vs. placebo	≈ 50% reduction in the number of exacerbations; improvement in lung function; ≈ 30% reduction in the daily oral corticosteroid dose. Data are reported vs. placebo
Most common adverse events	Patients aged 12 years or over: headache and injection site reactions. Children aged between 6 and 12 years: headache and pyrexia	Headache, injection site reactions, back pain	Increase in levels of the enzyme creatine phosphokinase in the blood, correlated with possible damage to muscles. Anaphylactic reactions may affect ≤ 1% patients	Headache, pharyngitis	Infections, eye disorders (conjunctivitis and related conditions) and injection site reactions

EMA European Medicines Agency, FDA US Food and Drug Administration, ICS inhaled corticosteroids, IL interleukin, LABA long-acting β₂ agonist, mAB monoclonal antibody