.

.

In this Launch Alert, Walter Liszewski, MD, discusses the recent FDA approval of remibrutinib (Rhapsido) for adults with symptomatic dermographism (SD) inadequately controlled with H1 antihistamines. As the first treatment specifically approved for a form of chronic inducible urticaria (CIndU), remibrutinib addresses a longstanding treatment gap for patients with persistent symptoms despite antihistamine therapy. Dr Liszewski reviews the clinical significance of the approval, key findings from the phase 3 RemIND trial, and considerations for incorporating remibrutinib into clinical practice.

Understanding symptomatic dermographism

Chronic urticaria, defined by recurrent wheals, angioedema, or both for more than 6 weeks, is broadly classified into chronic spontaneous urticaria (CSU) and CIndU. Unlike CSU, in which symptoms arise without a specific external trigger, CIndU is characterized by wheals or angioedema provoked by identifiable stimuli, such as cold, pressure, heat, or friction.

SD, the most prevalent subtype of CIndU, is characterized by the development of itchy, raised wheals in response to scratching or rubbing the skin. Symptoms can be unpredictable and disruptive, affecting sleep, concentration, and daily activities.

Addressing a longstanding treatment gap

Historically, there have been no treatment options specifically approved for CIndU. Although second-generation H1 antihistamines remain a mainstay of treatment, more than half of patients with SD may continue to experience symptoms despite antihistamine therapy.

Recent therapeutic advances have expanded treatment options for CSU, including the approvals of omalizumab, dupilumab, and remibrutinib. However, until now, no medication had received FDA approval specifically for CIndU.

The approval of remibrutinib for SD represents an important milestone, providing clinicians with an on-label treatment option for adults whose symptoms remain inadequately controlled with H1 antihistamines.

Clinical trial insights: Findings from RemIND

The FDA approval was supported by results from the SD cohort of the phase 3 RemIND trial, which evaluated remibrutinib in patients who remained symptomatic despite treatment with second-generation H1 antihistamines.

Disease activity was assessed using a standardized skin provocation test that applies controlled friction to the skin to evaluate wheal formation. Treatment response was measured using the Total Fric Score.

At Week 12, 29.3% of patients receiving remibrutinib achieved a complete response from hives, compared with 14.0% receiving placebo. Responses were observed as early as Week 2.

Across clinical trials through Week 24, remibrutinib demonstrated a safety profile consistent across the SD and CSU populations. The most commonly reported adverse events (incidence ≥3%) included nasal congestion, sore throat, and runny nose (nasopharyngitis), bleeding, headache, nausea, and abdominal pain.

Mechanism of action: Targeting mast cell activation

Remibrutinib is a highly selective, oral Bruton's tyrosine kinase (BTK) inhibitor. BTK plays an important role in intracellular signaling pathways involved in mast cell activation and degranulation.

By inhibiting BTK, remibrutinib interferes with signaling that contributes to the release of histamine and other inflammatory mediators responsible for the wheals, itching, and swelling associated with chronic urticaria.

Clinical perspective: What the approval means for patients

Dr Liszewski emphasizes the substantial burden SD can place on patients. Beyond the physical discomfort of itching and wheal formation, the unpredictable nature of symptoms can interfere with sleep, concentration, and daily activities, while visible skin reactions may contribute to embarrassment and social discomfort.

With an estimated 3 million or more individuals affected by SD in the United States, the availability of a specifically approved therapy has the potential to address an important unmet need.

The approval is also relevant to clinicians managing patients with overlapping forms of chronic urticaria. Approximately one-third of patients with CSU may also have a form of CIndU, most commonly SD. Remibrutinib is now FDA approved for adults with either CSU or SD inadequately controlled with H1 antihistamines, making it the only treatment currently indicated for both conditions.

For clinicians, Dr Liszewski highlights the importance of recognizing SD, assessing symptom control despite antihistamine use, and considering the newly available treatment option for appropriate patients.

Key takeaways

• First approval for CIndU: Remibrutinib is the first FDA-approved treatment specifically indicated for a form of chronic inducible urticaria, symptomatic dermographism

• Addressing an unmet need: Many patients with SD continue to experience symptoms despite H1 antihistamine therapy

• Phase 3 efficacy: In the RemIND trial, 29.3% of patients receiving remibrutinib achieved complete response from hives at Week 12, compared with 14.0% receiving placebo, with responses observed as early as Week 2

• Targeted mechanism: Remibrutinib selectively inhibits BTK signaling involved in mast cell activation and histamine release

• Clinical implications: With indications for both CSU and SD, remibrutinib offers an additional treatment option for adults whose chronic urticaria remains inadequately controlled with H1 antihistamines