Intranasal epinephrine spray ARS-2 may offer a safe and effective needle-free treatment alternative for chronic spontaneous urticaria, results from a phase 2 study suggested.

Epinephrine has been used for treating acute urticaria since 1939, the study authors noted, but use has declined with the rise of oral or injectable antihistamines.

Researchers, led by David I. Bernstein, MD, with Bernstein Clinical Research Center and the Division of Immunology, Allergy, and Rheumatology at the University of Cincinnati, Cincinnati, conducted the study, which was published online in the Journal of Allergy and Clinical Immunology: In Practice.

The trial was a single-dose, randomized, placebo-controlled, crossover efficacy study in which 21 adult patients, who were experiencing an acute flare of urticaria symptoms, were treated either with ARS-2 (1 mg or 2 mg) or with placebo.

Better Hive, Pruritus Scores

The researchers found that both 1- and 2-mg doses of ARS-2 resulted in lower patient-reported hive and pruritus scores and lower investigator-reported urticaria and erythema scores than placebo (P < .05 for both). Additionally, more patients in the intervention group vs the placebo group were considered by researchers to have been “effectively treated.” Patient-reported satisfaction scores were also significantly higher for both doses of the nasal spray than for placebo. Only minor adverse effects were reported, primarily nasal discomfort.

Relative to placebo, both doses of ARS-2 resulted in rapid symptom reduction. Researchers observed statistically significant differences in itch severity starting 5 minutes after the 2-mg dose and 15 minutes after the 1-mg dose. Statistically significant differences in hive severity were observed at 15 minutes post-dose for the 2-mg dose and 30 minutes after the 1-mg dose. “These significant differences were observed through 120 minutes post-dose for both itch severity and hive severity (P < .001),” the authors wrote.

Great for Those Afraid of Self-Injecting

“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,” said Andrea Arlene Pappalardo, MD, allergy service director and associate professor at the University of Illinois College of Medicine in Chicago. “Many of my patients who have suffered an allergic reaction before have questions about this, as they say they are just afraid to give themselves a shot.”

However, she noted, there are many needle-free options for chronic hives. Because this study looks at a new indication for nasal epinephrine that is not yet approved, “I would not yet feel comfortable giving this medication for a hive worsening, just yet. But this could be a good option for the future that avoids oral steroids.” She added that nasal epinephrine should not be the only treatment given for hives.

Pappalardo said resurrecting an older medication reimagined in a needle-free form “is a great idea.” She added, “I also appreciated that the 1-mg dosage, opposed to the 2-mg, may be sufficient in abating the urticarial eruption.”

Questions Surrounding No Cardiovascular Side Effects

She pointed out that no cardiovascular side effects were reported and highlighted that patients with cardiovascular disease were excluded.

“This may be a limit to clinical utility, as many people with chronic spontaneous urticaria, at least in my clinic, have some form of cardiovascular disorder,” she said.

The study authors noted that when nasal epinephrine first came to market, there was a concern about its effectiveness in life-threatening situations.

Pappalardo said with clinical practice to date, along with results of newer studies, this concern is lessening. “I do believe that there is an overall hesitance for those who have had severe anaphylactic reactions in the past that required multiple auto-injector dosages to make a switch, which I tend to agree with, as you do not typically switch from a regimen that works well.”

Bernstein reported receiving grant support from ALK-Abelló, Amgen, AstraZeneca, Genentech, GlaxoSmithKline, Novartis, Regeneron, Sanofi, and Teva and serving as an adviser for ALK America, Aquestive Therapeutics, Bryn, Gerson Lehrman, and Guidepoint Global. He reported being a consultant and/or adviser for ARS Pharma. Several co-authors also reported having ties to industry. Pappalardo reported having no relevant financial relationships.

Marcia Frellick is an independent, Chicago-based healthcare journalist and a regular contributor to Medscape Medical News.