Remibrutinib for Chronic Spontaneous Urticaria: Rapid Symptom Control With an Oral Treatment Option
Walter Liszewski, MD, walks through a case of antihistamine-refractory chronic spontaneous urticaria, highlighting treatment selection, patient preferences, and rapid symptom control with remibrutinib.
Case presentation and medical history summary:
A 40-year-old woman presented with an 8-week history of a pruritic rash characterized by near-daily flares. Individual lesions typically resolved within several hours, and the patient reported that heat and stress exacerbated her symptoms. She was unable to identify any other triggers.
The patient initially began taking fexofenadine 180 mg daily, increasing the dose to 360 mg twice daily after 2 weeks, with only mild improvement. She had no history of angioedema involving the lips, eyelids, hands, or feet and no known autoimmune disease.
Physical exam and lab results:
Physical examination revealed numerous wheals of varying sizes distributed across the trunk and extremities. No angioedema was observed.
Laboratory testing was not pursued based on the clinical presentation. The overwhelming majority of CSU cases are idiopathic, and allergy and lab testing will delay definitive treatment and increase health care costs.1
Despite scheduled antihistamine treatment, the patient continued to experience daily flares, reporting a worst itch numeric rating scale (NRS) score of 8/10 and a pain score of 7/10.
Diagnostic review:
The patient's history of recurrent, transient wheals occurring almost daily for eight weeks was consistent with chronic spontaneous urticaria (CSU). CSU is characterized by recurrent wheals, angioedema, or both for more than six weeks, with individual wheals typically resolving within 24 hours. Although angioedema may accompany CSU, it was absent in this patient.¹
CSU is generally diagnosed clinically, and extensive laboratory or allergy testing is not routinely indicated in the absence of findings suggesting an alternative diagnosis or underlying condition. A limited laboratory evaluation may be considered based on the clinical presentation, with additional testing guided by the patient's history and examination.¹
Unlike urticaria associated with identifiable external allergens, CSU typically occurs without a consistent external trigger. Its pathogenesis is heterogeneous and may involve autoimmune and autoallergic mechanisms that contribute to mast cell activation. Consequently, routine testing for environmental or food allergies is generally not indicated unless the clinical history suggests a specific allergic trigger.¹
If a patient with CSU is started on second-generation antihistamines and they fail to improve, per the International Guidelines, what is the minimum number of weeks patients must be on this therapy before they should be escalated to a systemic agent?
Treatment discussion and outcome:
Despite treatment with fexofenadine at an increased dose, the patient continued to experience daily urticarial flares and substantial pruritus, indicating inadequate disease control.
Second-generation H1-antihistamines are recommended as first-line treatment for CSU, with up-dosing to as much as four times the standard dose in patients who do not achieve adequate symptom control. For patients whose disease remains uncontrolled despite this approach, escalation to systemic therapy is recommended.¹
Given the patient's persistent symptoms, systemic treatment options were considered, including the injectable therapies omalizumab and dupilumab. However, the patient expressed a preference for oral therapy rather than injections. Remibrutinib, an oral Bruton's tyrosine kinase (BTK) inhibitor approved for adults with CSU who remain symptomatic despite H1-antihistamine treatment, was therefore selected.
Remibrutinib was initiated at a dose of 25 mg twice daily. Within several days, the patient's hives had resolved. At the 2-week follow-up, she remained free of hives, and both her worst itch NRS and pain scores had decreased to 0. By week 12, she continued to be free of hives and maintained a worst itch NRS of 0.
Clinical insight
This case illustrates the importance of reassessing disease control in patients with CSU who remain symptomatic despite antihistamine treatment. The availability of an oral targeted therapy provided an option aligned with this patient's treatment preference and was associated with rapid resolution of her symptoms.
References
References1
- Zuberbier T, Ansari ZA, Abdul Latiff AH, et al. The International Guideline for the Definition, Classification, Diagnosis and Management of Urticaria. Allergy. 2026;81(8):2582-2632. doi:10.1111/all.70210