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Our approach to selection of biologic agents for add-on therapy for severe asthma in adolescents and adults*

Agent and target	US FDA-approved age	Patient selection	Route	Dose	Dosing interval	Adverse effects
For patients with elevated IgE and sensitivity to perennial allergens^¶
Omalizumab (anti-IgE)	≥6 years	IgE 30 to 700 int. units/mL in United States; 30 to 1500 int. units/mL in Europe	SC	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%)
For patients with eosinophilic phenotype^¶
Mepolizumab (anti-IL-5)	≥6 years	Peripheral blood eosinophils ≥150/microL	SC	100 mg^Δ	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^§	First week, 400 mg once (given as two 200 mg injections), then 200 mg every 2 weeks	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^§	First week, 600 mg once (given as two 300 mg injections), then 300 mg every 2 weeks^◊	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%)
For patients with eosinophilic or noneosinophilic phenotype
Tezepelumab	≥12 years	No required minimum blood eosinophil count	SC	210 mg	Every 4 weeks	Antibody development (2%; neutralizing <1%) 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. Refer to UpToDate topic on management of severe asthma for additional details regarding choice of therapy and administration.

IgE: total serum immunoglobulin E; IL-5: interleukin-5; SC: subcutaneous injection; IV: intravenous infusion; FEV₁: forced expiratory volume in one second; TSLP: thymic stromal lymphopoietin.

* 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 2 hours after each of the first 3 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.

¶ For patients who meet criteria for both omalizumab and anti-eosinophil medications, selection of a biologic agent may be based on factors such as clinician experience with the agent, assessment of relative contributions of IgE-mediated allergic asthma and eosinophil mediated asthma, frequency of dosing, and availability.

Δ For children age 6 to 11 years, the dose of mepolizumab is 40 mg, subcutaneously, every 4 weeks.

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

§ Mepolizumab and dupilumab 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.

References:

US Food and Drug Administration. Omalizumab (Xolair). http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/103976s5225lbl.pdf.
European Medicines Agency. Xolair. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/000606/WC500057298.pdf.
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/2021/761224s000lbl.pdf.

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