Epinephrine Nasal Spray Shows Promise for Urticaria Flares

Phase 2 trial finds intranasal epinephrine spray may offer a safe, effective, and needle-free treatment option for chronic spontaneous urticaria.

Published on Feb. 23, 2026

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In a phase 2 trial, patients experiencing an acute urticaria flare who used an intranasal epinephrine spray reported better hive and pruritus scores compared to the placebo group. The spray, called ARS-2, was found to rapidly reduce itch and hive severity, with statistically significant differences observed as early as 5-15 minutes after administration. While only minor side effects were reported, some experts note the study excluded patients with cardiovascular disease, which may limit the spray's clinical utility.

Why it matters

Chronic spontaneous urticaria is a debilitating condition that can significantly impact a patient's quality of life. Current treatment options often involve oral or injectable antihistamines, which can have side effects. The development of a needle-free epinephrine spray provides a potentially safer and more convenient alternative, especially for patients who are afraid of self-injecting.

The details

The phase 2 study was a single-dose, randomized, placebo-controlled, crossover trial involving 21 adult patients experiencing an acute urticaria flare. Patients were treated with either a 1 mg or 2 mg dose of the intranasal epinephrine spray ARS-2 or a placebo. The researchers found that both doses of the spray resulted in lower patient-reported hive and pruritus scores, as well as lower investigator-reported urticaria and erythema scores, compared to placebo. More patients in the intervention group were also considered to have been 'effectively treated' by researchers. Patients reported higher satisfaction scores with the nasal spray versus placebo, and only minor adverse effects, primarily nasal discomfort, were observed.

  • The study was published online in the Journal of Allergy and Clinical Immunology: In Practice in 2026.

The players

David I. Bernstein, MD

Lead researcher of the study, affiliated with the Bernstein Clinical Research Center and the Division of Immunology, Allergy, and Rheumatology at the University of Cincinnati.

Andrea Arlene Pappalardo, MD

Allergy service director and associate professor at the University of Illinois College of Medicine in Chicago, who provided expert commentary on the study findings.

ARS Pharma

The company that developed the intranasal epinephrine spray ARS-2 used in the study.

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What they’re saying

“Needle-free epinephrine is a great option to have in our toolbox, especially for those who are afraid of needles or afraid of giving themselves an injection in the setting of an emergency, which is common.”

— Andrea Arlene Pappalardo, MD, Allergy service director and associate professor at the University of Illinois College of Medicine in Chicago (Medscape)

“I also appreciated that the 1-mg dosage, opposed to the 2-mg, may be sufficient in abating the urticarial eruption.”

— Andrea Arlene Pappalardo, MD, Allergy service director and associate professor at the University of Illinois College of Medicine in Chicago (Medscape)

What’s next

Further research is needed to evaluate the safety and efficacy of the intranasal epinephrine spray, particularly in patients with cardiovascular disease, before it can be widely recommended for the treatment of chronic spontaneous urticaria.

The takeaway

The development of a needle-free epinephrine spray provides a promising alternative treatment option for patients with chronic spontaneous urticaria, especially those who are hesitant to self-inject. However, more clinical data is needed to fully understand the spray's safety profile and potential limitations before it can be widely adopted.