Between the Lines: Remibrutinib and the Evolving CIndU Treatment Landscape

Chronic inducible urticaria (CIndU) remains an underrecognized and often undertreated group of disorders, with patients frequently living for years with symptoms that interfere with work, recreation, and everyday activities. In a recent Dermatology Times Between the Lines series, moderator Diego Ruiz Dasilva, MD, was joined by Lindsey Finklea, MD, to examine the clinical burden of CIndU, limitations of current treatment strategies, and findings from the phase 3 REMIND study evaluating remibrutinib.

Recognizing the Burden of CIndU

CIndU encompasses several distinct subtypes in which specific stimuli provoke wheals, angioedema, or both. Finklea estimated its global prevalence at approximately 0.5% to 1.5%, with symptomatic dermatographism accounting for roughly half of cases. Cold and cholinergic urticaria are also common, while solar, heat, aquagenic, vibratory, contact, and delayed pressure urticaria occur less frequently.

The experts emphasized that diagnosis begins with a careful history but can be strengthened through standardized provocation testing. Tools such as the FricTest and temperature testing can help clinicians objectively characterize disease and track response to therapy.

Beyond physical symptoms, CIndU can substantially affect quality of life. Patients may reorganize their lives around avoiding triggers, making disease burden easy to underestimate. Dasilva and Finklea shared examples of patients whose disease prevented participation in recreational activities or interfered with their ability to work, illustrating the importance of asking patients not only about hives but also how the disease affects daily life.

Where Antihistamines Fall Short

Second-generation H1 antihistamines remain first-line treatment for CIndU, but the panel highlighted their limitations. According to Finklea, standard dosing is effective in only approximately 20% to 50% of patients. Even after doses are increased, a substantial proportion remain inadequately controlled.

Finklea described a methodical approach to antihistamine up-titration, gradually increasing treatment over approximately 2 to 3 weeks while setting expectations with patients. She also stressed the importance of daily preventive dosing rather than waiting until symptoms appear.

The treatment gap becomes particularly apparent once patients fail higher-dose antihistamines. With no FDA-approved medication specifically for CIndU at the time of the discussion, clinicians have largely extrapolated treatment strategies from chronic spontaneous urticaria (CSU).

Why Target BTK?

Although the pathophysiology of CIndU has not been completely elucidated, mast cell activation appears to play a central role. Finklea explained that multiple immune pathways involved in mast cell activation converge on Bruton tyrosine kinase (BTK), making it an attractive therapeutic target.

Remibrutinib is a highly selective BTK inhibitor that acts downstream of the high-affinity IgE receptor. By inhibiting BTK signaling, the therapy is intended to interfere with mast cell degranulation and the subsequent release of histamine and inflammatory mediators.

This mechanism provided the rationale for evaluating remibrutinib across 3 clinically distinct CIndU populations in the REMIND study: symptomatic dermatographism, cold urticaria, and cholinergic urticaria.

Examining the Phase 3 REMIND Study

REMIND enrolled adults with CIndU who remained symptomatic despite background treatment with second-generation H1 antihistamines. Participants with symptomatic dermatographism, cold urticaria, or cholinergic urticaria were randomized to receive remibrutinib 25 mg twice daily or placebo.

The primary endpoint was assessed at week 12, with subtype-specific provocation testing used to determine complete response. Patients with symptomatic dermatographism were evaluated using the FricTest, cold urticaria was assessed through temperature testing, and cholinergic urticaria was evaluated using an exercise provocation test.

Dasilva and Finklea emphasized the rigor of the complete-response endpoint. Rather than simply requiring improvement, patients had to demonstrate no elicited hives following provocation.

Complete Responses Across CIndU Subtypes

At week 12, approximately 29% of patients with symptomatic dermatographism and cholinergic urticaria achieved complete responses with remibrutinib, approximately twice the placebo response. The largest effect was observed among patients with cold urticaria, with a complete response rate of 56.3%, more than 3 times the placebo rate.

The panel noted that these percentages should be interpreted in the context of the demanding endpoint. For symptomatic dermatographism, for example, complete response meant moving from substantial baseline disease activity to a FricTest score of zero, with no elicited wheal.

Responses also appeared relatively quickly. Significant differences in symptomatic dermatographism were evident by week 2 and persisted through weeks 12 and 24. The experts noted that longer-term follow-up will be important for understanding whether patients who do not initially achieve complete control may continue improving over time.

Defining Meaningful Treatment Success

Although complete response was the clinical trial goal, Dasilva and Finklea discussed whether total clearance should always be the only measure of treatment success in practice.

For the FricTest, a score of zero represents complete response, whereas a score of one reflects mild disease. Finklea said she would ideally like every patient to reach zero but considers one a practical goal for many patients, particularly because disease activity may fluctuate between visits.

The discussion underscored the importance of balancing objective measures with the patient's experience. A patient who does not meet a strict complete-response endpoint may still experience meaningful improvements in symptoms, daily activities, and quality of life.

Evaluating the Safety Profile

The panel also reviewed safety findings from the 24-week placebo-controlled period. Severe adverse events were comparable between treatment groups, and the overall findings were consistent with the larger remibrutinib CSU clinical development program. Most events were mild to moderate, discontinuation rates were low, and no deaths were reported.

Common events occurring at rates of 5% or greater, including respiratory infection, headache, and nausea, were similar between groups. Petechiae occurred in 5.2% of remibrutinib-treated patients compared with 1.8% of patients receiving placebo, prompting discussion about the importance of counseling patients about what to watch for during treatment.

The experts also emphasized the selectivity of remibrutinib and distinguished its safety profile from earlier BTK inhibitors developed in hematology and oncology.

Looking Toward a New CIndU Treatment Landscape

When considering advanced treatment, Finklea and Dasilva discussed remibrutinib alongside omalizumab and dupilumab. Omalizumab currently has the largest body of CIndU literature, although it does not carry a CIndU-specific indication. Evidence for dupilumab is more limited, and the experts noted the absence of head-to-head comparisons among these therapies.

Ultimately, treatment decisions will continue to depend on factors including CIndU subtype, age, comorbidities, available evidence, and patient preference.

For Finklea, the REMIND findings signal an important step toward addressing a persistent treatment gap, particularly for symptomatic dermatographism. The series concluded with optimism that greater recognition of CIndU, more objective assessment, and increasingly mechanism-based therapies could allow clinicians to offer patients a level of disease control that historically has been difficult to achieve.

As additional long-term data emerge, the findings may also help refine treatment guidelines and reshape expectations for what successful CIndU management can look like.

References

1. Dermatology Times. Efficacy and Safety of Remibrutinib in Chronic Inducible Urticaria: Results of Phase 3 RemIND. Dermatology Times. 2026. Accessed October 30, 2026.
2. Finklea L, Metz M, Hide M, et al. Remibrutinib in chronic inducible urticaria: results from the phase 3 REMIND study. Presented at: European Academy of Allergy and Clinical Immunology (EAACI) Congress 2026; June 12-15, 2026; Istanbul, Turkey.