Department of Internal Medicine, National Referral Center for Rare Systemic Autoimmune Diseases, Hospital Cochin, Paris, France.
National Referral Center for Hypereosinophilic Syndrome (CEREO), Department of Internal Medicine, Hopital Foch, Suresnes, France.
Ann Rheum Dis. 2023 Dec;82(12):1580-1586. doi: 10.1136/ard-2023-224624. Epub 2023 Aug 7.
Benralizumab is effective in the treatment of eosinophilic asthma and is being investigated for the treatment of other eosinophil-associated diseases. Reports on the use of benralizumab for the treatment of eosinophilic granulomatosis with polyangiitis (EGPA) are limited to case reports and small case series.
We conducted a multicentre, retrospective study including EGPA patients treated with off-label benralizumab. The primary endpoint was the rate of complete response defined as no disease activity (Birmingham Vasculitis Activity Score=0) and a prednisone dose ≤4 mg/day. Partial response was defined as no disease activity and a prednisone dose ≥4 mg/day.
Sixty-eight patients were included, including 31 (46%) who had previously received mepolizumab. The use of benralizumab was warranted by uncontrolled asthma in 54 (81%), persistent ear, nose and throat (ENT) manifestations in 27 (40%) and persistent glucocorticoids (GCs) use in 48 (74%) patients. Median (IQR) follow-up after starting benralizumab was 23 (9-34) months. Thirty-three patients (49%) achieved a complete response, 24 (36%) achieved a partial response and 10 (15%) did not respond. Among the 57 patients who initially responded, 10 (18%) eventually required further line treatments. GCs were discontinued in 23 patients (38%). Prior mepolizumab use was associated with a higher rate of primary failure (26.7% vs 5.4%, p=0.034) and less frequent GCs discontinuation (14.8% vs 55.9%, p=0.001). Vasculitis flares occurred in 7 patients (11%) and were associated with histological evidence of vasculitis and/or antineutrophil cytoplasmic antibodies positivity at benralizumab initiation (p=0.004).
Benralizumab appears to be an effective treatment for refractory asthma or ENT manifestations in EGPA and allows GC-sparing. However, its efficacy was lower after prior failure of mepolizumab.
贝那鲁肽在治疗嗜酸性粒细胞性哮喘方面具有显著疗效，目前正在研究用于治疗其他嗜酸性粒细胞相关疾病。有关贝那鲁肽治疗嗜酸性粒细胞性肉芽肿伴多血管炎（EGPA）的报告仅限于病例报告和小病例系列。
我们进行了一项多中心回顾性研究，纳入了接受贝那鲁肽超适应证治疗的 EGPA 患者。主要终点是完全缓解率，定义为无疾病活动（伯明翰血管炎活动评分=0）且泼尼松剂量≤4mg/天。部分缓解定义为无疾病活动且泼尼松剂量≥4mg/天。
共纳入 68 例患者，其中 31 例（46%）曾接受美泊利珠单抗治疗。54 例（81%）患者因哮喘控制不佳而使用贝那鲁肽，27 例（40%）患者因持续存在耳鼻喉症状，48 例（74%）患者因持续使用糖皮质激素（GCs）而使用贝那鲁肽。开始使用贝那鲁肽后中位（IQR）随访时间为 23（9-34）个月。33 例（49%）患者达到完全缓解，24 例（36%）患者达到部分缓解，10 例（15%）患者无反应。在 57 例最初有反应的患者中，10 例（18%）最终需要进一步治疗。23 例（38%）患者停用 GCs。既往使用美泊利珠单抗与原发治疗失败率较高相关（26.7% vs. 5.4%，p=0.034），GCs 停药率较低（14.8% vs. 55.9%，p=0.001）。7 例（11%）患者发生血管炎发作，与贝那鲁肽起始时存在血管炎组织学证据和/或抗中性粒细胞胞浆抗体阳性相关（p=0.004）。
贝那鲁肽似乎是治疗 EGPA 中难治性哮喘或耳鼻喉表现的有效治疗方法，可减少 GCs 的使用。然而，在美泊利珠单抗治疗失败后，其疗效降低。
