Remibrutinib met its primary endpoints in achieving complete response criteria across the three most common subtypes of chronic inducible urticaria in the phase 3 RemIND trial.

The oral, highly selective Bruton’s tyrosine kinase inhibitor roughly doubled the 12-week rate of complete response in symptomatic dermographism (29.3% vs 14%) and cholinergic urticaria (29.3% vs 15.8%), while the boost was even greater in cold urticaria (56.3% vs 14.6%). All three met statistical significance (all P ≤ .0229), according to the researchers.

These treatment effects atop background second-generation H1 antihistamines were sustained through week 24, as Martin Metz, MD, of Charité-Universitätsmedizin Berlin in Berlin, Germany, reported in a presentation at the European Academy of Allergy and Clinical Immunology (EAACI) 2026 Annual Congress. 

While antihistamines have been the first-line treatment for chronic inducible urticaria, no FDA-approved therapies exist for this group of rare conditions characterized by recurrent hives or angioedema in response to specific triggers. These triggers are friction on the skin in the case of symptomatic dermographism, cold exposure in cold urticaria, and an increase in body temperature in cholinergic urticaria.

“These are the most common [subtypes], and they can be quite debilitating. So, having a treatment that is approved for this type of hive, this subset of patients would be quite impactful,” said Jonathan A. Bernstein, MD, of the University of Cincinnati College of Medicine in Cincinnati, who was not involved with the trial.

Antihistamines fail to help many patients, said Metz, with up to 80% remaining symptomatic. “Beyond that, there is nothing we can do apart from explaining the disease to our patients,” Metz told Medscape Medical News.

While a minority of patients in RemIND had a complete response in symptomatic dermographism and cholinergic urticaria, the advantage over placebo was clinically meaningful, Bernstein said.

Sold as Rhapsido by Novartis, remibrutinib is approved for the treatment of chronic spontaneous urticaria. “Based on these data, I would expect that they should hopefully see if the FDA approves them for treatment of these types of inducible hives,” Bernstein said.

Because enrollment of the symptomatic dermographism cohort of RemIND finished faster than the other less common subtypes, Novartis already applied to the FDA for an expansion of the indication for remibrutinib to that subtype. The company plans to continue additional filings for other subtypes with health authorities globally throughout 2026, according to a spokesperson for the drug maker.

Metz said the effectiveness of the drug in the three most common forms of chronic inducible urticaria likely will carry over to rarer forms of the condition. “There is likely to be some variability, with possibly more complete responders in some and a little bit less in others. But overall, we expect to see efficacy” in any form, he said.

The trial enrolled 362 adults who had been diagnosed for at least 4 months and remained symptomatic despite treatment with second-generation histamine 1-receptor antagonist treatment: 115 with symptomatic dermographism, 96 with cold urticaria, and 151 with cholinergic urticaria. All participants were randomly assigned 1:1 to receive 25 mg of remibrutinib twice daily or placebo as an add-on to their antihistamine for 24 weeks, followed by an open-label period of remibrutinib up to week 52.

The primary endpoint of 12-week complete response differed across the subtypes. In symptomatic dermographism, it was a Total Fric Score of 0 following provocation (no linear hives with at least 3 mm width within 10 minutes of provocation with the FricTest tool). For cold urticaria, it was the critical temperature threshold (no wheals at ≤ 4°C on provocation with TempTest) and the Itch Numeric Rating Scale (complete absence of both wheals and itch in a pulse-controlled ergometry test).

Metz called the safety findings consistent with what has been known about remibrutinib from its use in chronic spontaneous urticaria. Adverse events were largely mild or moderate through week 24, with few adverse events that were serious or led to discontinuation. No deaths were reported.

Other therapies are in development for chronic inducible urticaria, notably inhibitors of the c-KIT receptor on mast cells, Bernstein said. “They seem promising as well,” he said, “but they have a lot of off-target side effects, for instance, graying of the hair and transient neutropenia.”

The trial was funded by Novartis Pharma AG.

Metz disclosed having served as an investigator for and/or received honoraria from companies including Novartis, AbbVie, Johnson & Johnson, and Eli Lilly.

Bernstein disclosed relationships with Novartis, Regeneron, Celldex Therapeutics, Intellia Therapeutics, and numerous other companies.

Crystal Phend is an award-winning medical journalist with decades of experience reporting on clinical research and healthcare developments across specialties. When not walking the halls at a medical conference, she can be found at a keyboard in upstate New York.