Tezepelumab Demonstrates Sustained Post-Treatment Reductions in CSU Disease Activity, Inflammatory Markers

Treatment with tezepelumab in individuals with chronic spontaneous urticaria (CSU) who were naïve to anti-IgE therapy was associated with sustained reductions in disease activity and levels of interleukin (IL)-5 and IL-3 at 32 weeks after treatment cessation, reductions that were not seen with either omalizumab or with placebo.

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The findings, presented at the 2024 American Academy of Allergy, Asthma, and Immunology (AAAAI) annual meeting point to a sustained effect of thymic stromal lymphopoietin (TSLP) blockade after ending treatment, according to presenting author Marcus Maurer, MD, professor of dermatology and allergy and executive director of the institute of Allergology at from Charite-Universitatsmedizin Berlin, and colleagues.

The AAAAI meeting is being held in Washington, DC, February 23-26, 2024.

Tezepelumab, a monoclonal antibody that inhibits TSLP, is an “upstream-targeted therapy” that the researchers say may have potential to block multiple pathways in CSU. In a late-breaking abstract session, Maurer presented results of the phase 2b INCEPTION study (NCT04833855), which evaluated the effects of tezepelumab in a group of anti-IgE-naïve individuals with CSU.

Investigators recruited adults with persistent CSU symptoms despite treatment with second-generation antihistamines. They randomly assigned participants in a 1:1:1:1 ratio to receive subcutaneous placebo, tezepelumab 210 mg every 4 weeks, tezepelumab 420 mg every 2 weeks, or omalizumab 300 mg every 4 weeks, for 16 weeks. (The study was not powered to compare tezepelumab with omalizumab, according to the abstract.)

The primary endpoint for INCEPTION was the change from baseline to week 16 in the Urticaria Activity Score over 7 days (UAS7). In exploratory analyses, the researchers evaluated tezepelumab efficacy after treatment discontinuation at study week 32 as well as levels of serum biomarkers IL-5 and IL-13.

The study cohort numbered 125 with 32 receiving placebo and 31 in each group receiving tezepelumab 210 mg, tezepelumab 420 mg, and omalizumab 300 mg.

Maurer and colleagues reported numeric improvement in UAS7 at week 16, however the primary endpoint was not met, according to the study abstract.

Least square mean (standard error):

• tezepelumab 210 mg, –17.0(2.0)
• tezepelumab 420 mg, –16.9(1.9)
• placebo –14.7(1.9); P > .05 tezepelumab vs placebo)
• omalizumab 300mg –19.5(2.0)

Sixteen weeks later, at week 32 and 18 to 20 weeks after the last dose was administered, the team did find significant improvements from baseline in UAS7:

• tezepelumab 210 mg, –18.0(2.1) (P = .037 vs placebo)
• tezepelumab 420 mg, –17.2(2.1)(P = .062 vs placebo)
• placebo, –11.7(2.1)
• omalizumab, not observed, –12.6 (2.1)

Further, according to the abstract, the sustained effect of tezepelumab was independent of participants’ baseline IgE and of changes in IgE on-study, and “occurred alongside continued reduction of IL-5 and IL-13.”

Tezepelumab is approved in the US s add-on maintenance treatment of adults, adolescents and children aged 12 years and older with severe, uncontrolled asthma.

Source: Maurer M, McLaren J, Chon Y, et al. Sustained improvements in UAS7 after 16-week treatment with tezepelumab in biologic-naïve adults with CSU: results of the phase 2b INCEPTION study. Abstract L39 presented at: 2024 American Academy of Allergy, Asthma, and Immunology Annual Meeting; February 23-26, 2024; Washington, DC. Accessed February 20, 2024. https://www.jacionline.org/pb-assets/Health%20Advance/journals/ymai/AAAAI_2024_February23-1707140438697.pdf