D2.466 - More options for the treatment of Chronic Spontaneous Urticaria: Tezepelumab

Thymic stromal lymphopoietin (TSLP) is an alarmin released by damaged endothelium that initiates and perpetuates the inflammatory cascade leading to the release of T2-dependent proinflammatory mediators. It has recently been shown to be elevated in patients with chronic spontaneous urticaria (CSU). Tezepelumab, a monoclonal antibody targeting the TSLP receptor, blocks this inflammatory cascade. Recent clinical trials have demonstrated its efficacy in the treatment of CSU, particularly in patients with low total IgE levels (<40 IU/mL).

Five patients with poorly controlled CSU (UAS >28, UCT <12) are presented. A complete urticaria workup was performed (complete blood count, biochemistry, immunoglobulins, ANA, serum protein electrophoresis, thyroid hormones, and serologies for HBV, HCV, HIV, hydatidosis, and stool parasites). All patients had previously received treatment with up to fourfold-dose H1-antihistamines, omalizumab 300–450 mg every 2–4 weeks, and cyclosporine (3.5 mg/kg/day) when not contraindicated. Two patients experienced partial response to cyclosporine, which was discontinued due to adverse effects (gastrointestinal symptoms and/or gingival hyperplasia). Following failure of prior therapies, subcutaneous tezepelumab 210 mg every 4 weeks was initiated in all cases under compassionate use, after obtaining informed consent.

Allergic evaluation showed low total IgE levels and an autoimmune profile. Despite treatment according to current EAACI international guidelines, patients had poor CSU control, impaired quality of life, multiple annual courses of oral corticosteroids, and frequent emergency department visits.

Tezepelumab 210mg every 4 weeks achieved clinical improvement and reduction in UAS in all five cases. Two patients remain asymptomatic (UAS 0) at 19 and 15 months of follow-up, respectively. The remaining three patients show good or partial disease control with tezepelumab combined with moderate doses of antihistamines (2–3 tablets/day).

Tezepelumab may represent a valid therapeutic option for CSU refractory to conventional treatments, particularly in patients with low total IgE levels and an autoimmune profile.