ABCs in Dermatology: 2026 CSU Guidelines Redefine Urticaria Treatment

Chronic spontaneous urticaria (CSU) is estimated to affect up to 20% of people at some point in their lifetime, and its updated international management guidance now reflects a therapeutic landscape far broader than the omalizumab-only paradigm dermatologists have relied on for over a decade.

On a recent episode of ABCs in Dermatology, hosts Lindsay Ackerman, MD, and Chris Bunick, MD, PhD, discussed the 2025-2026 update to the international urticaria guidelines, developed with input from more than 200 experts across nearly 60 countries and over 100 dermatology and allergy/immunology societies.

The guidelines reaffirm that more than half of CSU patients have an identifiable autoimmune mechanism, divided into type 1 (auto-allergic, driven by IgE autoantibodies to self-antigens) and type 2b (autoimmune, driven by IgG antibodies that activate mast cells). Low total IgE paired with elevated IgG antibodies to thyroid peroxidase is not a validated biomarker but may signal a type 2b phenotype and predict a blunted response to omalizumab.

The guidelines now recommend baseline complete blood count, C-reactive protein or erythrocyte sedimentation rate, total IgE, and IgG anti-thyroid peroxidase testing in specialized care settings to help guide agent selection, while explicitly discouraging extensive workup in acute urticaria.

The most consequential change is structural. Where omalizumab previously stood alone as the add-on option beyond antihistamines, the guidelines now position remibrutinib and dupilumab alongside it as advanced systemic therapies for antihistamine-refractory disease, with second-generation H1 antihistamines titrated up to fourfold dosing remaining first line.

Remibrutinib, an oral Bruton tyrosine kinase (BTK) inhibitor dosed at 25 mg twice daily, and dupilumab, an IL-4 receptor alpha antagonist that reduces IL-4 and IL-13 signaling, each received conditional recommendations based on phase 3 data. In the REMIX-1 and REMIX-2 trials, remibrutinib produced significantly greater Urticaria Activity Score over 7 days (UAS7) reductions than placebo by week 12, sustained through week 24, with a favorable safety profile aside from a modest increase in petechiae.2

In the LIBERTY-CSU CUPID trials, dupilumab improved UAS7 regardless of prior omalizumab exposure or response.3

Bunick noted that cross-trial comparison of UAS7 curves suggested remibrutinib reaches a 15-point improvement in roughly 2 weeks, compared with approximately 10 weeks for dupilumab, consistent with BTK inhibition's more upstream mechanism in mast cells and B cells.4

The guidelines also formalize outcome measures for practice, primarily UAS7, which separates skin (wheal) and itch subscores on a 0-to-42 scale, alongside the urticaria control test and disease-specific quality-of-life instruments. For patients with angioedema-predominant disease, the panel recommends checking complement C4 and C1 inhibitor levels to rule out hereditary or acquired angioedema.

Collectively, the update signals a shift from a single-agent bottleneck to individualized, mechanism-informed selection among 3 systemic options, a change both hosts characterized as likely to expand who can manage CSU beyond allergy and immunology and into broader dermatology practice.

Relevant disclosures for Bunick include AbbVie, South Beach Symposium, Almirall, Apogee Therapeutics, Arcutis Biotherapeutics, Daiichi Sankyo, Eli Lilly, LEO Pharma, US, Novan, Novartis, Ortho Dermatologics, Palvella Therapeutics, Pfizer Inc., Sanofi, Sun Pharmaceutical Industries Ltd., Timber Pharmaceuticals, and UCB. Relevant disclosures for Ackerman include AbbVie, Alumis, Amgen, Arcutis, Beiersdorf, Boehringer Ingelheim, Bristol Myers Squibb, Dermavant, Galderma, L'Oréal, Novartis, Sun Pharmaceutical, and UCB.

References

1. 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:https://doi.org/10.1111/all.70210

2. Maurer M, Casale TB, Saini SS, et al. Dupilumab in patients with chronic spontaneous urticaria (LIBERTY-CSU CUPID): Two randomized, double-blind, placebo-controlled, phase 3 trials. J Allergy Clin Immunol. 2024;154(1):184-194. doi:https://doi.org/10.1016/j.jaci.2024.01.028

3. Metz M, Giménez-Arnau A, Hide M, et al. Remibrutinib in Chronic Spontaneous Urticaria. N Engl J Med. 2025;392(10):984-994. doi:https://doi.org/10.1056/NEJMoa2408792

4. Giménez-Arnau AM, Szalewski R, Hide M, et al. Remibrutinib in chronic spontaneous urticaria: 52-week results from two phase 3 studies. J Allergy Clin Immunol. 2025;157(1):143-154. doi:https://doi.org/10.1016/j.jaci.2025.09.028