Biologics for Severe Asthma Present Opportunities for Pharmacists

The National Asthma Education and Prevention Guidelines define asthma as a chronic respiratory disease distinguished by reversible airflow obstruction, bronchial hyperresponsiveness, and airway inflammation.¹ According to recent CDC statistics, the disease affects almost 25 million individuals in the United States alone.² The Global Initiative for Asthma (GINA) estimates that 3% to 4% of sufferers have "severe asthma," defined as requiring optimized therapy with high-dose inhaled steroids plus a long-acting bronchodilator (LABA) for the past year, or maintenance oral corticosteroids for at least 6 months of the past year.³ Despite its low prevalence, severe asthma accounts for 60% of the costs of asthma treatment, primarily due to medication use.⁴

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PHARMACIST ROLE IN SEVERE ASTHMA TREATMENT

Over the past 2 decades, the FDA has approved 6 biologic agents to treat severe, uncontrolled asthma. These agents provide new treatment options for providers whose patients experience severe exacerbations, decreased lung function, and increased oral corticosteroid use.

Pharmacists' interactions with asthma patients may help them identify patients who would benefit from biologic therapy. Pharmacists may identify maintenance oral corticosteroid prescriptions or frequent bronchodilator use as part of an asthma drug therapy review. As an intervention, pharmacists may facilitate discussions between patients and providers and assist providers with selecting biologic therapy.

SEVERE ASTHMA ETIOLOGY

Severe asthma can take various forms, including allergic asthma, eosinophilic asthma, and a combination of both, each characterized by distinct biomarkers.⁴ According to GINA, the eosinophilic type is responsible for at least 50% of severe cases of asthma.³ Eosinophils are involved in the inflammatory cascade that responds to infection, allergen, or another foreign attack. Patients with eosinophilic asthma may also display comorbidities such as atopic dermatitis, chronic rhinosinusitis with nasal polyps (CRSwNP), or eosinophilic granulomatosis with polyangiitis.

BIOLOGIC OPTIONS

Biologics are the agents of choice when all other therapies are optimized and severe asthma remains uncontrolled. However, the choice of biologic is difficult due to differing patient presentations, diverse mechanisms of action, and overlap in their benefits.

The 6 available options are all humanized monoclonal antibodies but differ in several important ways (listed here in order of FDA approval for severe asthma):^6-11

• Omalizumab (Xolair; Genentech) is the oldest agent and works best against allergic asthma by inhibiting immunoglobulin-E-mediated inflammation.
• Reslizumab (Cinqair; Teva) is an interleukin-5 (IL-5) receptor blocker that interrupts the inflammatory cascade, preventing the release of eosinophils.
• Benralizumab (Fasenra; AstraZeneca) is an IL-5 inhibitor that also kills eosinophils directly.
• Dupilumab (Dupixent; Regeneron & Sanofi) blocks IL-4 and IL-13 at the IL-4 receptor alpha site on inflammatory cells. As a result, dupilumab inhibits the creation of various inflammatory cytokines and Ig-E.
• Mepolizumab (Nucala; GlaxoSmithKline) is an IL-5 antagonist.
• Tezepelumab-ekko (Tezspire; AstraZeneca and Amgen) inhibits thymic stromal lymphopoietin, an alarmin-class cytokine that works in the early stages of the inflammatory process.

CHOICE OF THERAPY

Many considerations guide the provider's choice of agent, including those listed below:^6-13

1. Type of severe asthma: The FDA has approved omalizumab for allergic asthma and mepolizumab, dupilumab, benralizumab, and reslizumab for eosinophilic asthma.Providers may use tezepelumab for all subtypes of severe asthma.
2. Desired outcomes: Only dupilumab is FDA-approved for reducing oral corticosteroid use. A comparative meta-analysis concluded that benralizumab, dupilumab, mepolizumab, and tezepelumab decreased the frequency of exacerbations, but benralizumab was less effective than the others. In a separate meta-analysis comparing 5 agents (all except mepolizumab), dupilumab and tezepelumab were better at decreasing exacerbations, improving lung function, and reducing hospitalizations than the others.
3. Cost/Insurance coverage: Because these medications are expensive specialty agents, pharmacists and providers must consider the patient's copay, the tier on the insurance formulary, and the necessity of completing prior authorizations.
4. Dosing considerations: Prescribers must administer reslizumab intravenously, whereas the others are subcutaneous injections that patients can administer at home. Providers may also consider the frequency of administration, which can range from every 2 weeks to every 8 weeks.
5. Comorbidities: The FDA approved dupilumab for atopic dermatitis, CRSwNP, and other potential comorbid conditions. Providers may also choose mepolizumab and omalizumab to treat asthma and CRSwNP as FDA-approved indications.

CONCLUSION

Although a small percentage of patients with asthma suffer from severe, uncontrolled disease, they represent a significant burden to the health care system. They also present an opportunity for pharmacists to recommend biologic therapies that are proven to reduce exacerbations, reduce steroid use, and improve outcomes.

REFERENCES

1. National Asthma Education and Prevention Program. Expert Panel Report 3 (EPR-3): Guidelines for the Diagnosis and Management of Asthma-Summary Report 2007. J Allergy Clin Immunol. 2007 Nov;120(5 Suppl):S94-138. doi: 10.1016/j.jaci.2007.09.043. Erratum in: J Allergy Clin Immunol. 2008 Jun;121(6):1330. PMID: 17983880.

2. 2.Most Recent National Asthma Data. Centers for Disease Control and Prevention. Accessed April 25, 2024.https://www.cdc.gov/asthma/most_recent_national_asthma_data.htm

3. Global Strategy for Asthma Management and Prevention. Global Asthma Initiative. Updated 2020. Accessed April 25, 2025. https://ginasthma.org/wp-content/uploads/2020/04/GINA-2020-full-report_-final-_wms.pdf

4. Sadatsafavi M, Lynd L, Marra C, Carleton B, Tan WC, Sullivan S, Fitzgerald JM. Direct health care costs associated with asthma in British Columbia. Can Respir J. 2010 Mar-Apr;17(2):74-80. doi: 10.1155/2010/361071. PMID: 20422063; PMCID: PMC2866215.

5. Caminati M, Buhl R, Corren J, et al. Tezepelumab in patients with allergic and eosinophilic asthma. Allergy. 2023 Dec 26. doi: 10.1111/all.15986. Epub ahead of print. PMID: 38146651.

6. Xolair. Prescribing Information. Genentech, Inc.: February 2024: https://www.gene.com/download/pdf/xolair_prescribing.pdf

7. Cinqair. Prescribing Information. Teva Respiratory, LLC; February 2020. https://www.cinqair.com/globalassets/cinqair/prescribinginformation.pdf

8. Fasenra. Prescribing Information. AstraZeneca AB; April 2024. https://den8dhaj6zs0e.cloudfront.net/50fd68b9-106b-4550-b5d0-12b045f8b184/3647bed4-ce91-4fe7-9bc5-32dbee73f80a/3647bed4-ce91-4fe7-9bc5-32dbee73f80a_viewable_rendition__v.pdf

9. Dupixent. Prescribing Information. Regeneron and Sanofi. January 2024. https://www.regeneron.com/downloads/dupixent_fpi.pdf

10. Nucala. Prescribing Information. GlaxoSmithKline LLC. March 2023. https://gskpro.com/content/dam/global/hcpportal/en_US/Prescribing_Information/Nucala/pdf/NUCALA-PI-PIL-IFU-COMBINED.PDF

11. Tezspire. Prescribing Information. Amgen and AstraZeneca AB. February 2023: https://den8dhaj6zs0e.cloudfront.net/50fd68b9-106b-4550-b5d0-12b045f8b184/e306dc06-d580-4457-b15f-9f28545ad63a/e306dc06-d580-4457-b15f-9f28545ad63a_viewable_rendition__v.pdf

12. Nopsopon T, Lassiter G, Chen ML, et al. Comparative efficacy of tezepelumab to mepolizumab, benralizumab, and dupilumab in eosinophilic asthma: A Bayesian network meta-analysis. J Allergy Clin Immunol. 2023 Mar;151(3):747-755. doi: 10.1016/j.jaci.2022.11.021. Epub 2022 Dec 17. PMID: 36538979; PMCID: PMC9992307.

13. Pitre T, Jassal T, Angjeli A, et al. A comparison of the effectiveness of biologic therapies for asthma: A systematic review and network meta-analysis. Ann Allergy Asthma Immunol. 2023 May;130(5):595-606. doi: 10.1016/j.anai.2022.12.018. Epub 2022 Dec 20. PMID: 36563746.