Efficacy and safety of rituximab in the treatment of eosinophilic granulomatosis with polyangiitis
Efficacy and safety of rituximab in the treatment of eosinophilic granulomatosis with polyangiitis
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DOI：
10.1136/rmdopen-2019-000905
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发表时间：
2019-04-01
期刊：
影响因子：
6.2
通讯作者：
Jayne, David
中科院分区：
文献类型：
--
作者：
Teixeira, Vitor;Mohammad, Aladdin J.;Jayne, David
简介 嗜酸性肉芽肿性多血管炎 (EGPA) 是抗中性粒细胞胞浆抗体 (ANCA) 相关性血管炎的一个亚型，具有独特的病理生理机制、临床特征和治疗反应。利妥昔单抗是治疗肉芽肿性多血管炎和显微镜下多血管炎的许可疗法，但利妥昔单抗治疗 EGPA 的经验有限。 方法 对来自三级中心、接受利妥昔单抗治疗大多数难治性 EGPA 或环磷酰胺禁忌症的 EGPA 患者进行研究。在初始治疗时收集标准化数据集，并在 24 个月内每 3 个月收集一次。缓解定义为伯明翰血管炎活动评分 (BVAS) 为 0，部分缓解定义为 BVAS 较基线降低≥ 50%。缓解定义为泼尼松龙剂量 >= 5 mg 时 BVAS 为 0。 结果 2003 年至 2017 年间，69 名患者（44 名女性）接受了利妥昔单抗治疗。6 个月时观察到改善（缓解和部分缓解）的患者为 76.8%，12 个月时为 82.8%，24 个月时为 93.2%，而复发发生在 2017 年。 24 个月时为 54%，其中哮喘是最常见的表现。中位 BVAS 从基线时的 6 降至 6 个月时的 1，以及 12 和 24 个月时的 0。泼尼松龙剂量（毫克/天，中位）在第 6、12 和 24 个月时分别从 12.5 减少至 7、7.5 和 5。 ANCA 阳性患者的哮喘/耳鼻喉 (ENT) 无复发生存时间较长，缓解时间较短。 讨论 利妥昔单抗在 EGPA 中显示出一定疗效，并导致泼尼松龙需求量减少，但尽管继续治疗，哮喘和 ENT 复发率仍然很高。 ANCA 阳性子集似乎对孤立的哮喘/耳鼻喉科恶化有更持续的反应。
Introduction Eosinophilic granulomatosis with polyangiitis (EGPA) is a subset of antineutrophil cytoplasmic antibodies (ANCA) associated vasculitis with distinct pathophysiological mechanisms, clinical features and treatment responses. Rituximab is a licensed therapy for granulomatosis with polyangiitis and microscopic polyangiitis but there is limited experience of rituximab in EGPA.Methods EGPA patients from a tertiary centre who received rituximab for mostly refractory EGPA or in whom cyclophosphamide was contra indicated were studied. A standardised dataset was collected at time of initial treatment and every 3 months for 24 months. Response was defined as a Birmingham Vasculitis Activity Score (BVAS) of 0 and partial response as >= 50% reduction in BVAS from baseline. Remission was defined as a BVAS of 0 on prednisolone dose >= 5 mg.Results Sixty-nine patients (44 female) received rituximab between 2003 and 2017. Improvement (response and partial response) was observed in 76.8% of patients at 6 months, 82.8% at 12 months and in 93.2% by 24 months, while relapses occurred in 54% by 24 months, with asthma being the most frequent manifestation. The median BVAS decreased from 6 at baseline to 1 at 6 months, and 0 at 12 and 24 months. Prednisolone dose (mg/day, median) decreased from 12.5 to 7, 7.5 and 5 at 6, 12 and 24 months, respectively. ANCA positive patients had a longer asthma/ear, nose and throat (ENT) relapse-free survival time and a shorter time to remission.Discussion Rituximab demonstrated some efficacy in EGPA and led to a reduction in prednisolone requirement, but asthma and ENT relapse rates were high despite continued treatment. The ANCA positive subset appeared to have a more sustained response on isolated asthma/ENT exacerbations.