A recent phase 3 clinical trial has revealed significant findings on the efficacy and safety of benralizumab, an eosinophil-depleting anti–interleukin-5 receptor α monoclonal antibody, in treating eosinophilic esophagitis (EoE). The study, published in The New England Journal of Medicine, shows that benralizumab is significantly more effective than a placebo in achieving a histologic response in patients with EoE.
Benralizumab treats eosinophilic esophagitis (EoE) by targeting the interleukin-5 receptor (IL-5R) on eosinophils. It blocks IL-5 signaling, which is essential for eosinophil survival and function, and induces antibody-dependent cell-mediated cytotoxicity (ADCC) to destroy eosinophils. This dual action significantly reduces eosinophil levels in the esophagus, thereby decreasing inflammation and alleviating symptoms such as difficulty swallowing, food impaction, and esophageal pain.
The double-blind, randomized, placebo-controlled trial involved 211 patients aged 12 to 65 years with symptomatic and histologically active EoE. Patients were randomly assigned in a 1:1 ratio to receive either subcutaneous benralizumab (30 mg) or placebo every four weeks. The primary efficacy endpoints were achieving a histologic response, defined as ≤6 eosinophils per high-power field, and the change from baseline in the dysphagia symptom questionnaire (DSQ) score at week 24. The DSQ score ranges from 0 to 84, with higher scores indicating more frequent or severe dysphagia symptoms.
At the 24-week mark, 87.4% of patients receiving benralizumab achieved the histologic response compared to just 6.5% in the placebo group. This represents a significant difference of 80.8 percentage points (95% confidence interval [CI], 72.9 to 88.8; P<0.001), underscoring the efficacy of benralizumab efficacy in reducing eosinophil levels in the esophagus.
However, the results were less encouraging regarding symptomatic relief. The change from baseline in DSQ scores did not show a statistically significant difference between the benralizumab and placebo groups (difference in least-squares means, 3.0 points; 95% CI, –1.4 to 7.4; P=0.18). Additionally, no substantial difference was observed between the two groups in the Eosinophilic Esophagitis Endoscopic Reference Score, which measures endoscopic abnormalities. Safety profiles for benralizumab were consistent with previous studies, with adverse events reported in 64.1% of the benralizumab group and 61.7% of the placebo group. Importantly, no patients discontinued the trial due to adverse events, suggesting that benralizumab is well-tolerated.
EoE is a chronic immune system disease characterized by the accumulation of eosinophils in the esophagus, leading to inflammation and damage. Patients with EoE often experience difficulty swallowing and food impaction, significantly impacting their quality of life. Epidemiologic studies have documented EoE cases globally, with the incidence ranging from 0.1 to 1.2 per 10,000 people. Current treatments for EoE include dietary management, corticosteroids, and proton pump inhibitors. However, there is a continuous search for more effective and targeted therapies. In this context, the results of the benralizumab trial offer new insights into the treatment landscape for this chronic condition.
These results indicate that while benralizumab is highly effective in achieving histologic remission in EoE patients, its impact on dysphagia symptoms remains limited. The disconnect between histologic and symptomatic improvement highlights the complexity of EoE and suggests that eosinophil depletion alone may not be sufficient to alleviate all clinical symptoms. In a study, Pyne et.al., also concluded that benralizumab is effective in eosinophil depletion and has some improvement in symptoms of EoE.
In conclusion, this trial demonstrates the potential of benralizumab as a histologic treatment for EoE, offering hope for better disease management. However, searching for treatments that can significantly improve histologic and symptomatic outcomes continues. Further research is needed to explore combination therapies or additional targets to provide comprehensive relief for EoE patients.
References
- Rothenberg ME, Dellon ES, Collins MH, Bredenoord AJ, Hirano I, Peterson KA, et al. Eosinophil Depletion with Benralizumab for Eosinophilic Esophagitis. New England Journal of Medicine. 2024 Jun 26;390(24):2252–63.
- Pyne AL, Uchida AM, Hazel MW, Stubben CJ, Chang JW, Bailey DD, et al. Effect of benralizumab on histopathology and inflammatory signatures in a clinical cohort of eosinophilic esophagitis. Diseases of the Esophagus. 2024 Jul 11;doae031.
- Roussel JM, Pandit S. Eosinophilic Esophagitis. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 [cited 2024 Jul 30]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK459297/