Indications, dosing, and adverse effects of biologic agents used for severe asthma^*

Agent and target	US FDA-approved age	Approved indication^¶	Route	Dose	Dosing interval	Adverse effects
Omalizumab (anti-IgE)	≥6 years	IgE 30 to 700 int. units/mL in United States; 30 to 1500 int. units/mL in Europe	SC^Δ	Based on weight and IgE Doses ≥225 mg need to be divided over >1 injection site Maximal dose: 375 mg every 2 weeks in United States; 600 mg every 2 weeks in Europe	2 to 4 weeks depending on IgE level and body weight	Local injection site reaction (severe 12%), usually within 1 hour Thromboembolic disease ≤3% Anaphylaxis, immediate or delayed <1% Antibody development (<1%)
Mepolizumab (anti-IL-5)	≥6 years	Peripheral blood eosinophils ≥150/microL	SC^Δ	Adults and adolescents: 100 mg Children age 6 to 11 years: 40 mg	4 weeks	Headache (19%) Local injection site reaction (8 to 15%) Anaphylaxis: Immediate or delayed <1% Human anti-human neutralizing antibody (<1%) Herpes zoster (<1%): Administration of zoster vaccine is suggested prior to initiation
Benralizumab (anti-IL-5 receptor alpha)	≥12 years	Peripheral blood eosinophils ≥150/microL	SC	30 mg	4 weeks for first 3 doses, then 8 weeks	Human anti-human antibody development (13%; neutralizing 12%) Headache 8% Fever 3% Hypersensitivity (anaphylaxis, angioedema, urticaria; 3%): typically within hours of injection but can be delayed (3%)
Dupilumab (anti-IL-4 receptor subunit alpha)^§	≥6 years	Peripheral blood eosinophils ≥150/microL	SC^Δ	Adults and adolescents: First week, 400 mg once (given as two 200 mg injections), then 200 mg Children age 6 to 11 years: 100 mg^◊, for children 15 to <30 kg; 200 mg, for children ≥30 kg	2 weeks	Human anti-human antibody development in patients receiving the 300 mg dose every 2 weeks for 52 weeks (6%; 2% neutralizing antibodies) and in patients taking 200 mg dose every 2 weeks for 52 weeks (9%; 4% neutralizing antibodies) Transient eosinophilia (4%); over 3000 cells/mL (1.2%) Anaphylaxis and other hypersensitivity reactions (<1%) Injection site reactions, conjunctivitis, keratitis, oral and other herpes simplex viral infections
Dupilumab (anti-IL-4 receptor subunit alpha)^§	≥6 years	Peripheral blood eosinophils ≥150/microL	SC^Δ	First week, 600 mg once (given as two 300 mg injections), then 300 mg^§	2 weeks
Reslizumab (anti-IL-5)	≥18 years	Peripheral blood eosinophils ≥400/microL	IV	3 mg/kg	4 weeks	Human anti-human antibody development (5%) Anaphylaxis 0.3% during infusion or within 30 minutes after infusion; may occur as early as second dose or can be delayed Transient increase in creatine phosphokinase (20%)
Tezepelumab	≥12 years	No additional requirements	SC^Δ	210 mg	Every 4 weeks	Antibody development (2%; neutralizing <1%) Anaphylaxis and hypersensitivity reactions typically within hours but can be after days

These agents are for use in patients with uncontrolled asthma despite regular use of a combination of medium- to high-dose inhaled glucocorticoid and long-acting beta-2 agonists and FEV₁ <80% predicted. For patients who meet indications for multiple biologic agents, our approach to selection is based on several factors including assessment of type 2 allergic comorbidities, timing of disease-onset, allergen sensitivity, blood eosinophil level, and fraction of exhaled nitric oxide. Refer to UpToDate topic on management of severe asthma and accompanying algorithm on biologic agent selection for additional details regarding choice of therapy and administration.

FEV₁: forced expiratory volume in one second; IgE: total serum immunoglobulin E; IL-5: interleukin-5; IV: intravenous infusion; SC: subcutaneous injection; TSLP: thymic stromal lymphopoietin; US FDA: United States Food and Drug Association.

* Helminth infection should be excluded or treated prior to initiation of therapy. These agents should be administered in a setting prepared to handle anaphylaxis. Patients should be observed for two hours after each of the first three injections and for 30 minutes after each subsequent injection. It is advised that patients receiving omalizumab should carry an epinephrine autoinjector for at least 24 hours after each injection due to late occurrences of anaphylaxis.

¶ This column notes indications in addition to the diagnosis of poorly controlled severe asthma despite inhaled therapies, which is required for all biologic agents.

Δ Mepolizumab, dupilumab, and tezepelumab can be administered at home after appropriate training. Omalizumab is available for home administration in some countries, including the United States. Refer to UpToDate content for additional information.

◊ For children age 6 to 11 years 15 to <30 kg with severe asthma, dupilumab may also be dosed 300 mg every four weeks. Alternative dosing regimens are used for moderate to severe atopic dermatitis.

§ The higher dose of dupilumab is advised for adults or adolescents with oral glucocorticoid-dependent asthma or comorbid moderate to severe atopic dermatitis.

References:

US Food and Drug Administration. Omalizumab (Xolair). http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/103976s5225lbl.pdf.
European Medicines Agency. Xolair. https://www.ema.europa.eu/en/medicines/human/EPAR/xolair.
Cox L, Platts-Mills TAE, Finegold I et al. American Academy of Allergy, Asthma and Immunology/American College of Allergy, Asthma and Immunology Joint Task Force Report on omalizumab-associated anaphylaxis. J Allergy Clin Immunol 2007;120:1373-77.
US Food and Drug Administration. Mepolizumab (Nucala). https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/125526s012,761122s002s003lbl.pdf.
US Food and Drug Administration. Reslizumab (Cinqair) prescribing information. https://www.cinqair.com/globalassets/cinqair/prescribinginformation.pdf.
US Food and Drug Administration. Benralizumab (Fasenra). https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761070s000lbl.pdf.
US Food and Drug Administration. Dupilumab (Dupixent). https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761055s007lbl.pdf.
US Food and Drug Administration. Tezepelumab (Tezspire). https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/761224s001lbl.pdf.

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Indications, dosing, and adverse effects of biologic agents used for severe asthma*

Indications, dosing, and adverse effects of biologic agents used for severe asthma^*