Breakthrough in urticaria therapy: First oral BTK inhibitor drug awaits EU approval

Chronic spontaneous urticaria (CSU) – the enigmatic skin disease with itchy welts that often lasts for months or years – affects almost 4 million people in Europe. Over 50% remain symptomatic despite antihistamines. Now there is hope: On February 26, 2026, the European Medicines Agency (EMA) issued a positive recommendation for remibrutinib (Rhapsido®) – the first oral BTK inhibitor for CSU. Two identical Phase III trials (REMIX-1 & 2, n=925) show that 31% of patients became completely symptom-free (vs. 10% placebo, p<0.001), with itch reduction as early as week 1 and sustained effects over 52 weeks. But how exactly does the BTK inhibitor work? Who is it suitable for? And what does this mean for you as an affected individual? This article explains the latest findings – practical and evidence-based.

What the Phase III trials show

The EMA's positive recommendation is based on two large, identical clinical trials: REMIX-1 (n=470) and REMIX-2 (n=455). A total of 925 patients participated who continued to suffer from severe itching and hives despite standard therapy with H1 antihistamines. The study design was randomized, double-blind, and placebo-controlled, with participants receiving either remibrutinib (25 mg twice daily) or a placebo in a 2:1 ratio. The results are clear and significant.

• UAS7 reduction (combined score of itching and wheals): -20.0 points vs. -13.8 (placebo), p<0.001 (REMIX-1).

• 31.1% of participants became completely symptom-free (UAS7=0) vs. only 10.5% in the placebo group (p<0.001).

• 49.8% achieved very good symptom control (UAS7≤6) vs. 24.8% with placebo (p<0.001).

• Onset of effect: A significant improvement was measurable from the first week.

• Long-term effect: The effect persisted for over 52 weeks (average UAS7 reduction of -23.22).

• Responder rate: Approximately 50% of patients achieve good to very good control of their symptoms.

• The data were published in the prestigious New England Journal of Medicine (NEJM 2024), which speaks to the highest scientific quality.

Mechanism: How does remibrutinib work?

You might be wondering what makes remibrutinib different from your previous medications. While antihistamines only block histamine after it has already been released, remibrutinib works a step earlier. It is a highly selective inhibitor of Bruton's tyrosine kinase (BTK). This enzyme plays a key role in the activation of mast cells and basophils – precisely the cells that "go haywire" in urticaria.

• BTK (Bruton tyrosine kinase) is a central "switch enzyme" inside immune cells (mast cells, basophils).

• Remibrutinib highly selectively blocks this enzyme, thus stopping the faulty signaling cascade.

• The result: The mast cells are "calmed" and can no longer release histamine explosively.

• Since histamine is the main trigger of itching, hives and swelling, the symptoms are tackled at their root.

• Additionally, remibrutinib reduces the release of other inflammatory mediators such as cytokines and leukotrienes.

• In contrast to antihistamines, the cause of cell activation is blocked, not just the symptom.

• The medication is available orally (tablet); no injections are needed.

• Important: It does not cause widespread suppression of the immune system (immunosuppression) like some biologics.

Dosage & Application

Using remibrutinib is remarkably simple and can be easily integrated into daily life. The dosage studied in the trials and now recommended is fixed and does not need to be gradually increased. This makes starting therapy straightforward.

• Standard dose: 25 mg twice daily as a tablet (total dose 50 mg per day).

• Dosage: Ideally, take in the morning and evening, regardless of meals.

• First effects: Many patients experience a significant reduction in itching as early as day 7.

• Optimal effect: Full effectiveness is usually achieved after about 12 weeks.

• Duration of use: The therapy should be carried out for at least 12 weeks, but is also suitable as long-term therapy.

• No dose titration needed: You start immediately with the full effective dose.

• No laboratory monitoring required: Regular blood tests (e.g., liver function tests) are not required.

• If no improvement occurs after 12 weeks (non-response), the therapy should be reviewed with the doctor.

For whom is remibrutinib particularly suitable?

Not every urticaria patient needs this new medication immediately. It's specifically designed for those who don't respond well to standard therapy. If you still suffer from hives and itching despite taking antihistamines daily (even at higher doses), remibrutinib could be the next step.

• Adults with chronic spontaneous urticaria (CSU) who remain symptomatic despite H1 antihistamines.

• Patients who wish to avoid injections (as with biologics) and prefer a tablet.

• People with moderate to severe urticaria (UAS7 score ≥16).

• Responder rate: Approximately 50% achieve a UAS7≤6 (well controlled), approximately 30% become completely symptom-free.

• Particularly effective for: severe itching, frequent hives and high levels of suffering.

• Not suitable for: pregnant and breastfeeding women (safety data is lacking) and children under 18 years of age.

• It represents an important alternative for patients who do not respond to omalizumab (the previous biologic) (non-responders).

Comparison: Remibrutinib vs. other CSU therapies

To understand where remibrutinib stands, it's worth comparing it to existing treatment options. It fills the gap between simple tablets (antihistamines) and injections (biologics).

• H1 antihistamines (standard): They work very quickly (30-60 min), but often only provide insufficient relief from symptoms (50% non-responders).

• Remibrutinib: Onset of action somewhat slower (from 7 days), but causal therapy through BTK blockade with 30% symptom relief.

• Omalizumab (biologic): It is injected every 4 weeks, approximately 40% become symptom-free, but it is significantly more expensive and complex.

• Remibrutinib vs. Omalizumab: The main difference is the route of administration (oral vs. injection) with comparable efficacy.

• Combination with antihistamines: Is possible and often recommended in practice (maintain basic therapy).

• Advantages of remibrutinib: No refrigerator needed, no doctor's appointments for injections, ideal for travel.

• Disadvantage: You have to remember to take it twice a day (compliance), whereas the injection is only given once a month.

Side effects & contraindications

Safety is paramount with new medications. The 52-week study data show a favorable profile. Remibrutinib was generally well tolerated, and side effects were mostly mild to moderate.

• Most common side effects (≥3%): Nasopharyngitis (cold symptoms), headache and mild nausea.

• Petechiae: Small, pinpoint skin hemorrhages occurred in 3.8% of patients (vs. 0.3% with placebo), which were mostly harmless.

• No liver safety concerns: Over 52 weeks, no increased risk of liver damage was observed (a problem with earlier BTK inhibitors).

• No serious adverse events occurred more frequently in the remibrutinib group than in the placebo group.

• Contraindications: Pregnancy, breastfeeding, and severe liver disease are exclusion criteria.

• Interactions: Caution is advised when taking strong CYP3A4 inhibitors (e.g., ketoconazole, certain antibiotics) at the same time.

• Long-term use: Safety is well documented up to 52 weeks; the profile remained constant.

• Discontinuation: No rebound effect was observed – the symptoms do not return suddenly or in a worsened form.

Limitations of the studies

Despite the positive data, there are points we need to examine critically. No study is perfect, and questions remain that only long-term practical experience will clarify.

• Study duration: The data extends to a maximum of 52 weeks – long-term effects over several years are still unknown.

• Adults only: There is currently no approved data for children and young people under 18 years of age.

• Non-responders: Approximately 30% of patients remain symptomatic even under remibrutinib; the reason for this (genetic factors?) is unclear.

• Lack of head-to-head comparisons: There is no direct comparative study against omalizumab to see which one really works "better".

• Costs & Availability: The final price in the EU and the eligibility for reimbursement by health insurance companies are not yet clear.

⚠️ Important note: This information is for general informational purposes only and does not constitute medical advice. Remibrutinib is not yet approved in the EU (approval expected in 2026). If you have chronic urticaria, please always consult a dermatologist or allergist. The dosages and instructions for use mentioned here are based on study data and do not replace individual medical advice.

Sources:

1. Giménez-Arnau A, et al. Remibrutinib in Chronic Spontaneous Urticaria. New England Journal of Medicine. 2024;391:XXX-XXX. DOI: 10.1056/NEJMoa2408792

2. Giménez-Arnau A, et al. Remibrutinib in chronic spontaneous urticaria: 52-week results from two phase 3 studies. Journal of Allergy and Clinical Immunology. 2026;157(1):143-154. DOI: 10.1016/j.jaci.2025.09.028

3. European Medicines Agency (EMA). CHMP Meeting Highlights, 23-26 February 2026. https://www.ema.europa.eu/en/news/meeting-highlights-committee-medical-products-human-use-chmp-23-26-february-2026