Tezepelumab for the treatment of chronic spontaneous urticaria: Results of the phase 2b INCEPTION study

BACKGROUND: Tezepelumab, an mAb inhibiting thymic stromal lymphopoietin, is an upstream-targeted therapy with potential to inhibit multiple pathways in chronic spontaneous urticaria (CSU). OBJECTIVE: antihistamines. METHODS: This phase 2b study randomized 183 patients (125 anti-IgE therapy-naive; 58 anti-IgE therapy-experienced) to placebo every 2 weeks, tezepelumab 210 mg every 4 weeks, tezepelumab 420 mg every 2 weeks, or omalizumab 300 mg every 4 weeks (anti-IgE-naive only) for 16-week treatment. The primary end point was change from baseline in weekly Urticaria Activity Score (UAS7) at week 16. Safety and exploratory end points were evaluated through week 32. RESULTS: The 16-week primary end point was not met. In the overall population, tezepelumab 210 mg and 420 mg did not significantly improve UAS7 versus placebo (least squares mean [SE]: -13.5 [1.6] and -14.7 [1.5], respectively, vs -13.6 [1.6], P = .99, nominal and P = .60, nominal, respectively). Greater improvement in UAS7 versus placebo was observed in the anti-IgE-naive tezepelumab-treated populations (nominal significance); a trend toward significance was observed with omalizumab. In the anti-IgE-naive 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 end point was not met, tezepelumab showed post-treatment reductions in CSU activity through week 32, suggesting a delayed, sustained, thymic stromal lymphopoietin blockade treatment effect.