To the best of our knowledge, this is the first case of EoE complicated by severe asthma that improved clinically and histologically improvement and went into remission after being treated with benralizumab. In this case, although 20 mg/day of prednisolone and budesonide oral therapy reduced peripheral blood eosinophilia, they were ineffective. After the addition of benralizumab, the patient’s clinical symptoms significantly improved, and prednisolone administration was successfully discontinued. Furthermore, after discontinuing benralizumab, the patient had no EoE recurrence for more than 6 months.
In EoE, IL-5/IL-5Rα signaling promotes esophageal remodeling, while in asthma, it promotes bronchial wall remodeling [20]. When compared to wild-type mice, IL-5-deficient mice were protected from the development of esophageal remodeling. Furthermore, esophageal collagen and basal layer thickness were increased in transgenic mice overexpressing IL-5 [21]. Therefore, anti-IL-5 and anti-IL-5Rα antibodies may be effective in preventing esophageal remodeling caused by EoE. In addition, benralizumab can function as an affcosylated antibody with increased antibody-dependent cellular cytotoxicity (ADCC) against IL-5Rα expressed cells including eosinophils [22]. Because of its ADCC function, benralizumab has the potential to reduce eosinophils more rapidly and effectively than mepolizumab and reslizumab [23]. Based on these findings, benralizumab was approved for the treatment of severe asthma in the United States, Europe, and Japan in 2017–2018 [24]. Furthermore, the U.S. Food and Drug Administration granted benralizumab Orphan Drug Designation for the treatment of eosinophilic polyangiitis granuloma and EoE in August 2019. In line with these findings, some case studies report the clinical efficacy of anti-IL-5 or anti-IL-5Rα antibodies against EoE [25–32]. Previous case reports have demonstrated that the temporal efficacies of benralizumab against EoE, however, several digestive symptoms remained or relapsed even during treatment [30–31]. In contrast, our patient experienced complete rapid remission of clinical symptoms as well as endoscopic- and histologic findings after benralizumab administration. Furthermore, the patient was still in remission more than 4 years after starting benralizumab despite her clinical characteristics and examination findings appearing similar to her previous reports. One reason for the high treatment efficacy is that our patient was treated with benralizumab in addition to rabeprazole sodium, budesonide and prednisolone unlike previous reports. Like treating multiple drug combinations in severe asthma, it is possible that the treatment with multiple drugs affected the therapeutic effect of complete remission.
We did not observe any side effects in this patient after administering benralizumab, even in combination with other several drugs, indicating that benralizumab could be well tolerated even by elderly patients. Benralizumab’s safety profile had previously been evaluated in the SIROCCO, CALIMA, ZONDA, and MELTEMI trials for patients from 10 to 75 years of age with severe EA [33]. These pivotal trials demonstrated good tolerability during 5 years of follow-up, with the benralizumab group experiencing no more adverse events than the placebo group. The incidence of serious infections, hypersensitivity reactions and malignancies were 5 (1.1%), 23 (5.2%) and 3 (0.7%), respectively, with no deaths during the treatment period and the most commonly reported adverse events were nasopharyngitis (11.9%), asthma (7.4%), headache (5.0%), and bronchitis (4.3%) [33]. Furthermore, no concomitant medications have been reported for benralizumab. These results suggesting that combination treatment strategies including benralizumab may be preferable for elderly patients who usually take many medications. On the other hand, if we had diagnosed EoE earlier and intervened with treatment, this patient could have avoided suffering from long-term gastrointestinal symptoms. Widespread recognition of EoE and advances in diagnostic techniques for early detection will be needed, as well as further elucidation of the pathogenesis of the disease.
In our case, benralizumab in combination with other multiple drugs significantly improved the symptoms and examination findings of an elderly Asian woman with EoE. Furthermore, she experienced no side effects or recurrence even after discontinuing benralizumab withdrawal, indicating that benralizumab is an appropriate therapeutic option for such patients. Large-scale studies are expected to determine the optimal efficacy and safety of benralizumab against EoE, particularly in elderly patients who are resistant to PPIs and steroid therapy.