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Arjan Bredenoord, MD, details how tezepelumab's selective TSLP inhibition sustained EoE remission through week 52 of the CROSSING trial.
Tezepelumab (Tezspire) produced sustained histologic remission and dysphagia symptom improvement through week 52 in patients with eosinophilic esophagitis (EoE), meeting both co-primary and all key secondary endpoints in the phase 3 CROSSING trial, according to AstraZeneca and Amgen.1,2
Investigators enrolled patients who remained symptomatic and histologically active despite maintenance therapy, a population in which roughly a quarter to half fail to achieve adequate control with first-line options or cannot tolerate them. Tezepelumab, a first-in-class monoclonal antibody targeting thymic stromal lymphopoietin (TSLP), has already demonstrated efficacy in severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP), making EoE its third epithelial-driven inflammatory indication.3 The FDA granted tezepelumab orphan drug designation for EoE in October 2021.4
"Tezepelumab is very effective in patients with eosinophilic esophagitis, both adolescents and adult patients," said CROSSING investigator Arjan Bredenoord, MD, gastroenterologist and professor, Amsterdam University Medical Center, in an interview with HCPLive. “It reduces, and in most cases completely results in, histologic remission, [along with] substantial symptomatic improvement.”
CROSSING is a randomized, double-blind, placebo-controlled, multicenter, parallel-group phase 3 trial evaluating subcutaneous tezepelumab dosed every 4 weeks against placebo in patients aged 12 to 80 years with symptomatic, histologically active EoE.¹ Investigators randomized 368 patients in a 1:1:1 ratio to a low dose of tezepelumab, a high dose, or placebo, with stable background EoE medications, including proton pump inhibitors and swallowed topical corticosteroids.¹ Bredenoord noted patients on stable background therapy in both study arms continued to experience symptoms and inflammation, limiting any influence on the placebo-adjusted comparison.
At week 24, tezepelumab produced statistically significant improvement in histologic remission, defined as a peak esophageal eosinophil count of 6 eosinophils per high-power field or fewer, compared with placebo.¹ The trial's second co-primary endpoint, mean change from baseline in the 4-item Dysphagia Symptom Questionnaire (DSQ) scored from 0 to 84 over 14-day intervals, also favored tezepelumab.¹ Both co-primary results were sustained through week 52 in the low- and high-dose arms, though exact effect sizes have not yet been released and are expected at an upcoming medical meeting.
Key secondary endpoints assessed histologic remission and dysphagia symptoms at week 52, along with endoscopic disease features measured by the EoE Endoscopic Reference Score (EoE-EREFS) and histologic severity and extent measured by the EoE Histology Scoring System (EoE-HSS) at weeks 24 and 52.¹ Additional week 52 secondary endpoints, including endoscopic response, inflammatory remission, and total endoscopic remission, all favored tezepelumab over placebo.¹ Bredenoord said endoscopic improvement tracked closely with histologic findings, with reductions in edema and other inflammatory signs visible on repeat endoscopy.
"This medicine also works for other atopic conditions, such as allergic asthma,” Bredenoord said. "If a patient has both asthma and eosinophilic esophagitis, this treatment could be a solution for both diseases, instead of prescribing different treatments for each."
The safety profile observed in CROSSING was generally consistent with tezepelumab's established profile in its approved indications, according to AstraZeneca, with no new safety signals identified across either dose arm.¹
AstraZeneca and Amgen plan to present full safety and secondary endpoint data from CROSSING at the United European Gastroenterology (UEG) Week meeting in Barcelona in October 2026, with regulatory submissions to follow.¹ Tezepelumab is currently approved for severe asthma and for CRSwNP in the US and other regions.3
Bredenoord has no reported disclosures.
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