To the Editor, Eosinophilic granulomatosis with polyangiitis (EGPA) is a systemic necrotizing vasculitis that occurs in individuals with a history of bronchial asthma or allergic disease, and is characterized by peripheral eosinophilia and eosinophilic inflammation of multiple organs. Allergic manifestations such as asthma or allergic rhinitis typically precede the vasculitic phase, during which both ischemic injury and eosinophil-mediated inflammation contribute to organ damage 1–3. Histopathological studies have demonstrated that activated eosinophils undergo eosinophil extracellular trap cell death (EETosis), releasing cytoplasmic granule proteins and galectin-10, which promote vascular injury and thrombosis 4,5. To suppress eosinophilic activation, mepolizumab, an anti-interleukin-5 monoclonal Ab, has been used effectively 6. More recently, benralizumab, an anti-interleukin-5 receptor monoclonal Ab, has emerged as an alternative therapeutic option 7. Although both drugs target eosinophilic inflammation, they differ in mechanism, dosing frequency, and cost. Data on the clinical impact of switching from mepolizumab to benralizumab in patients with established EGPA remain scarce 8–10. Belarizumab received health insurance approval in Japan in January 2025. Regarding frequency and cost: Mepolizumab (100 mg) requires 3 subcutaneous injections per monthly treatment (¥479,673-/3 syringes/3 pens), while Benralizumab (300 mg) requires 1 subcutaneous injection per treatment (¥335,309-/syringe, ¥351,731-/pen). The cost difference per treatment is ¥144,364 for the syringe and ¥127,942 for the pen. The annual difference (13 treatments/52 wk) is ¥1,876,732 for the syringe and ¥1,663,246 for the pen. After providing the above information to our outpatient patients, we implemented a drug switch at their request, despite no significant issues with their previous treatment course. We retrospectively analyzed 6 patients with EGPA who had been treated with mepolizumab for over 1 year and were subsequently switched to benralizumab at our outpatient clinic. Clinical symptoms, laboratory data, and pulmonary function were compared between the pre-switch period (mepolizumab) and 3 months after switching to benralizumab. Statistical analysis was performed using paired t-tests (Table 1). Table 1. - Patient characteristics and changes in body weight and laboratory parameters before and after switching therapy 0 Month 3 Month P value Patiants (N = 6) Body weight (kg) 55.3 ± 9.0 57.0 ± 9.5 0.005 6 Labo deta WBC (/μL) 7,338.3 ± 1,138.5 7,046.7 ± 1,424.7 6 Eosinophils (/μL) 33.2 ± 8.6 0 ± 0 0.003 6 ACTH (pg/mL) 10.1 ± 4.8 2.3 ± 1.0 0.003 4 Cortisol (μg/mL) 2.3 ± 1.0 0.9 ± 0.5 0.003 4 TARC (pg/mL) 617.7 ± 180.5 444 ± 131 0.001 6 IgE (IU/mL) 417.5 ± 130.3 355.7 ± 167.4 0.001 6 MPO-ANCA (IU/mL) ND (<1.0) ND (<1.0) 6 Six patients were included (ACTH and cortisol were not measured in patients off prednisolone). Paired t-tests were performed to compare laboratory data before switching and 3 months after switching to benralizumab. Statistical significance was defined as P < 0.05. Other routine laboratory parameters relevant to EGPA disease activity are summarized in the table.ACTH, adrenocorticotropic hormone; MPO-ANCA, myeloperoxidase–antineutrophil cytoplasmic antibody; IgE, immunoglobulin E; TARC, thymus and activation-regulated chemokine; WBC, white blood cell. At baseline, all patients were clinically stable under mepolizumab therapy, with a mean prednisolone (PSL) dose of 3.5 mg (range 1–8 mg) and a mean Birmingham Vasculitis Activity Score (BVAS) of 5.3 (range 1–9). Asthma and neurological symptoms were well controlled (Supplemental Tables 1–3, https://links.lww.com/PA9/A93). However, patients expressed a preference for benralizumab due to its less frequent administration and lower treatment cost. After switching to benralizumab, all 6 patients showed weight gain, which we interpreted as improved activity and appetite associated with better asthma control. Laboratory data revealed a significant decrease in peripheral eosinophil counts and serum thymus and activation-regulated chemokine levels. In the 4 patients who continued PSL, adrenocorticotropic hormone and cortisol levels decreased significantly after switching to benralizumab but remained within the normal range, and no clinical signs of adrenal insufficiency were observed. Symptom assessment indicated that disease control appeared to be improved or maintained overall. No significant worsening was observed in airway inflammation or pulmonary function tests. While some indicators showed significant changes in certain items, various biases exist, suggesting that further observation is necessary. Combining these findings, switching from mepolizumab to benralizumab does not worsen EGPA activity and may instead contribute to improvements in eosinophilic conditions, asthma control, and respiratory function. For example, regarding weight changes, the Japanese Ministry of Health, Labour and Welfare guidelines also mention symptoms caused by vasculitis among the primary clinical findings of EGPA 11. Regarding other vasculitis-related symptom changes, detailed BVAS assessment items showed that changes in scores for cardiovascular and neurological items contributed to overall BVAS improvement (Fig. 1A–F). Therefore, weight change may be related to vascular inflammation.Figure 1.: Changes in questionnaire scores, airway allergic inflammation, and pulmonary function after switching from mepolizumab to benralizumab. Questionnaire data were obtained from 6 patients; physiological tests were performed in 5 patients. (A) Birmingham Vasculitis Activity Score (BVAS) as an indicator of EGPA disease activity (N = 6); the vertical axis is the BVAS scores. (B) Asthma control test (ACT) as a marker of asthma control (N = 6); the vertical axis is ACT scores. (C) Fractional exhaled nitric oxide (FeNO) as a marker of eosinophilic airway inflammation (N = 5); the vertical axis is FeNO (ppb). (D) Neuropathic pain screening (NPS) score for EGPA-related neuropathic symptoms (N = 6); the vertical axis is the BVAS scores. Paired t-tests were used to compare pre- and post-switch results. Statistical significance was defined as P < 0.05. (E and F) pulmonary function tests showing total lung capacity (TLC: L) and diffusing capacity for carbon monoxide (DLCO: mL/min/mmHg) (N = 6 and 5, respectively). One patient was excluded (N = 5) from physiological testing because cognitive impairment prevented proper instruction compliance. *P < 0.05 compared with preswitch values (0 month). EGPA, eosinophilic granulomatosis with polyangiitis.Although the sample size was limited, no worsening of control was observed across multiple clinical parameters following the switch. This suggests benralizumab as a switch option for maintenance therapy in EGPA patients receiving mepolizumab 9,10,12. When selecting between mepolizumab and benralizumab, it is also important to consider multiple factors, such as patient burden (number of injections) and economic impact. This study had a small number of cases, a short observation period, and was influenced by seasonal changes. Therefore, it is important to conduct a prospective cohort study with a sufficient number of cases over a full year. This study received ethical from the Institutional Review Board of Saitama Medical University Hospital (Chairperson Prof. Yasuhito Terui, approved numbers: 2025-095, C-T2025-0213, approval date September 26, 2025), and was registered in the UMIN Clinical Trials Registry (UMIN: 000059198). Regarding the publication of this study, we have posted a notice on our hospital website using an opt-out format, and we have confirmed the explanation and consent of outpatients and recorded it in their medical records. Acknowledgements We sincerely thank the nursing staff of the Departments of General Internal Medicine and Respiratory Medicine at Saitama Medical University Hospital for their valuable support. Our study did not receive any research funding from the commercial or public sectors. This study was approved by the local Ethics Committee of Saitama Medical University Hospital (Chairperson Prof. Yasuhito Terui, approved numbers: 2025-095, C-T2025-0213, approval date September 26, 2025), and was registered in the UMIN Clinical Trials Registry (UMIN: 000059198). Conflicts of interest The authors have no financial conflicts of interest. Author contributions Takao Atsumi and Takehito Kobayashi designed the study. Takehito Kobayashi and Kazuyuki Nakagome performed the experiments using conventional methods. Takehito Kobayashi, Takashi Ishiguro, and Makoto Nagata analyzed the data. Takehito Kobayashi, Tomoyuki Soma, Yotaro Takaku, Tomoko Suzuki, and Keiji Yamamoto drafted the manuscript. All authors read and approved the final manuscript.
Kobayashi et al. (Fri,) studied this question.