Tezepelumab for the Treatment of Chronic Spontaneous Urticaria: Results of the Phase 2b INCEPTION Study.

Abstract

Background: Tezepelumab, a monoclonal antibody inhibiting thymic stromal lymphopoietin (TSLP), is an upstream-targeted therapy with potential to inhibit multiple pathways in chronic spontaneous urticaria (CSU).

Objective: To evaluate tezepelumab efficacy and safety in CSU patients despite sgAH treatment.

Methods: This phase 2b study randomized 183 patients (125 anti-IgE therapy-naïve; 58 anti-IgE therapy-experienced) to placebo Q2W, tezepelumab 210 mg Q4W, tezepelumab 420 mg Q2W, or omalizumab 300 mg Q4W (anti-IgE-naïve only) for 16-week treatment. The primary endpoint was change from baseline in UAS7 at week 16. Safety and exploratory endpoints were evaluated through week 32.

Results: The 16-week primary endpoint was not met: In the overall population, tezepelumab 210 mg and 420 mg did not significantly improve UAS7 versus placebo (LSM [SE]: -13.5 [1.6] and -14.7 [1.5], respectively, vs -13.6 [1.6], p = 0.99, nominal and p = 0.60, nominal, respectively). Greater improvement in UAS7 versus placebo was observed in the anti-IgE-naïve tezepelumab-treated populations (nominal significance); a trend toward significance was observed with omalizumab. In the anti-IgE-naïve population there was delayed, sustained, 32-week off-treatment improvement in UAS7 versus placebo with tezepelumab 210 mg (nominally significant) and 420 mg (trend), but not with omalizumab. This effect was larger in patients with lower baseline IgE levels and longer CSU duration and accompanied sustained IL-5 and IL-13 reductions. Tezepelumab and placebo safety findings were balanced.

Conclusion: Although the 16-week primary endpoint was not met, tezepelumab showed post-treatment reductions in CSU activity through week 32, suggesting a delayed, sustained, TSLP blockade treatment effect.