Rituximab therapy for refractory autoimmune bullous diseases: A multicenter, open-label, single-arm, phase 1/2 study on 10 Japanese patients
Rituximab therapy for refractory autoimmune bullous diseases: A multicenter, open-label, single-arm, phase 1/2 study on 10 Japanese patients
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DOI：
10.1111/1346-8138.14732
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发表时间：
2019-02-01
影响因子：
3.1
通讯作者：
Amagai, Masayuki
中科院分区：
文献类型：
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作者：
Kurihara, Yuichi;Yamagami, Jun;Amagai, Masayuki
这是一项利妥昔单抗（一种针对CD20的嵌合单克隆免疫球蛋白G抗体）治疗难治性自身免疫性大疱性疾病（天疱疮和类天疱疮）的多中心研究。10例患者（3例寻常型天疱疮，6例落叶型天疱疮，1例大疱性类天疱疮）接受单周期利妥昔单抗治疗（每周输注4次，剂量为375 mg/m2体表面积）。主要终点是严重不良事件的数量和40周时的完全缓解率。5例患者（50%）在最低限度治疗后达到完全缓解（定义为无活动性病变，全身皮质类固醇剂量低于泼尼松龙10 mg/天）。在4名未能达到完全缓解的天疱疮患者中观察到临床评分（天疱疮疾病面积指数）的改善和血清中自身抗体滴度的降低。这表明利妥昔单抗在10例中的9例中有效。观察到两起严重不良事件（卡氏肺孢子虫肺炎和感染性关节炎引起的败血性休克），并通过住院进行了充分治疗。外周血中的CD 19阳性B淋巴细胞在利妥昔单抗治疗后第29天减少，并且在整个观察期（280天）保持在低水平。我们的研究结果证实了利妥昔单抗治疗难治性自身免疫性大疱性疾病在日本的疗效。
This was a multicenter study of rituximab, a chimeric monoclonal immunoglobulin G antibody directed against CD20, for the treatment of refractory autoimmune bullous diseases (pemphigus and pemphigoid). Ten patients (three with pemphigus vulgaris, six with pemphigus foliaceus and one with bullous pemphigoid) were treated with a single cycle of rituximab (four weekly infusions at a dose of 375 mg/m(2) of body surface area). The primary end-points were the number of serious adverse events and rate of complete remission at 40 weeks. Five patients (50%) achieved complete remission with minimal therapy (defined as no active lesions with lower doses of systemic corticosteroids compared to that with prednisolone 10 mg/day). Improvements in clinical scores (Pemphigus Disease Area Index) and decreases in autoantibody titers in the sera were observed in the four pemphigus patients who failed to achieve complete remission. This suggests that rituximab was effective in nine of 10 cases. Two serious adverse events (Pneumocystis carinii pneumonia and septic shock due to infectious arthritis) were observed and adequately treated with hospitalization. CD19-positive B lymphocytes in the peripheral blood decreased on day 29 following rituximab treatment, and remained at low levels throughout the observation period (280 days). Our results confirmed the efficacy of rituximab therapy for refractory autoimmune bullous diseases in Japan.