Dupilumab, Tezepelumab Provide Consistent Real-World Severe Asthma Outcomes

Type 2 inflammation-targeting biologic therapies dupilumab (Dupixent) and tezepelumab (TEZSPIRE) provided similar reductions in exacerbations, eosinophil levels, and inhaler and corticosteroid use in patients with severe asthma, according to new analyses.1

A retrospective cohort study presented at the American College of Chest Physicians (CHEST) 2025 Annual Meeting in Chicago, IL, this week showed comparable real-world outcomes and benefits between dupilumab and tezepelumab in patients with severe asthma. The data, presented by Palwasha Zafar, MD, also showed a slightly increased rate of adverse tvents among patients receiving dupilumab — as well as a greater tendency for clinicians to prescribe tezepelumab to patients with more baseline comorbidities and medication use.

The findings provide real-world insights into potential personalized prescribing strategies for patients with severe asthma at a time when type 2 pathway-targeting biologics have become increasingly prominent in pulmonary disease. Just this last week, the US Food and Drug Administration (FDA) approved tezepelumab for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP) — joining biologics including dupilumab in having the distinction of being indicated for multiple inflammatory airway diseases.2

What are the differences between dupilumab and tezepelumab?

While both agents are indicated to treat patients with severe asthma, they offer differing methodology in doing so. An interleukin-4 and -13 (IL-4; IL-13) pathway inhibitor, dupilumab targets the main pathways of type 2 inflammatory disease. Dupilumab became the first biologic indicated to treat eosinophilic COPD in 2024 — adding a pathway-targeting agent to the armamentarium of symptom relief-oriented options already available for patients.

Tezepelumab is a thymic stromal lymphopoietin (TSLP) inhibitor that intervenes at a higher level in the cascade of inflammatory disease, meaning it is efficacious for both eosinophilic and non-eosinophilic asthma. It was approved in 2021 as the first biologic indicated for severe asthma regardless of patient eosinophil count.3

How do dupilumab and tezepelumab compare in real-world severe asthma outcomes?

Zafar and colleagues assessed data from 69 healthcare organizations from 2015 – 2023. Patients with asthma treated with either dupilumab or tezepelumab; those receiving another biologic therapy or who had a comorbidity including COPD or bronchiectasis were excluded from the analysis. The team used propensity score matching for demographics, body mass index, comorbidities (including gastroesophageal reflux disease [GERD], dermatitis, and eczema), serum eosinophils, immunoglobulin E (IgE) levels, baseline inhaler use, and systemic steroid therapy.

They sought primary outcomes including asthma exacerbations, systemic corticosteroid use, and inhaler changes among patients receiving either dupilumab or tezepelumab. Secondary outcomes of the assessment included eosinophil reduction and adverse events associated with either biologic.

Prior to propensity score matching, Zafar and colleagues noted that patients treated with dupilumab were significantly younger on average (mean age, 37 vs 49 years old). They were also more likely to be male (42.2% vs 25.4%). The most common comorbidities in patients treated with dupilumab were dermatitis and eczema (38.6%), as well as atopic dermatitis (16.4%). Approximately 30% of all patients being treated with tezepelumab had comorbid GERD.

The team also observed that the tezepelumab cohort was more likely to use bronchodilators, sympathomimetics, anticholinergics, and systemic steroids at baseline than the dupilumab cohort. But the dupilumab cohort reported a greater rate of obesity, as well as a higher mean baseline eosinophil count than the tezepelumab cohort (5.4±5.5 vs 2.0±2.5).

Following propensity matching (n = 949 per cohort), investigators observed similar asthma exacerbation rates between the dupilumab (22.0%) and tezepelumab cohorts (22.2%; P = .91). Patients treated with dupilumab were slightly more likely to use a systemic corticosteroid (45.2% vs 40.6%; P = .04) and report an inhaler change (67% vs 63%; P = .03).

The dupilumab reported slightly greater mean reductions in eosinophil count (2.37±2.4 vs 1.72±1.7; P = .15). However, patients receiving dupilumab more frequently reported adverse events including dermatitis, acute pharyngitis, conjunctivitis, acute tonsilitis, and headache (23.7% vs 17.5%; P <.01). There were no significant differences in mechanical ventilation use among patients receiving either dupilumab or tezepelumab.

In reviewing the findings, Zafar and colleagues noted that prior research directly comparing the real-world outcomes of treating severe asthma with dupilumab or tezepelumab is limited. While the two agents showed similar efficacy in reducing asthma exacerbations, there were distinct differences in secondary outcomes with either option.

“Dupilumab was associated with greater eosinophil reduction but higher adverse event rates, while tezepelumab had lower adverse events and was used more frequently in patients with higher baseline comorbidities and medication use,” they wrote. “These evidence-based findings offer valuable guidance for clinicians to personalize therapy, taking into account individual patient needs, insurance coverage limitations, specific side effect profiles, and personal treatment preferences.”

References

1. Zafar P, Gupta N, Javed A, Ilyas R, et al. Comparative Outcomes of Dupilumab and Tezepelumab in Asthma Management: A Real-World Analysis. Poster presented at: CHEST Annual Meeting 2025. Chicago, IL. October 19 – 22, 2025.
2. Johnson V. FDA Approval Adds Tezepelumab to CRSwNP Treatment Landscape. HCPLive. Published online October 17, 2025. https://www.hcplive.com/view/fda-approval-adds-tezepelumab-crswnp-treatment-landscape
3. Johnson V. Biologic Decision-Making in Asthma and COPD: Prioritizing Earlier, Precise Intervention. HCPLive. Published online June 16, 2025. https://www.hcplive.com/view/biologic-decision-making-asthma-copd-prioritizing-earlier-precise-intervention