Rituximab for the treatment of patients with autoimmune hepatitis who are refractory or intolerant to standard therapy
Rituximab for the treatment of patients with autoimmune hepatitis who are refractory or intolerant to standard therapy
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DOI：
10.1155/2013/512624
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发表时间：
2013-05-01
影响因子：
2.7
通讯作者：
Myers, Robert P.
中科院分区：
文献类型：
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作者：
Burak, Kelly W.;Swain, Mark G.;Myers, Robert P.
背景：虽然大多数自身免疫性肝炎(AIH)患者对泼尼松和/或硫唑嘌呤治疗有反应，但一些患者对标准治疗不耐受或难治。利妥昔单抗是一种抗CD20单抗，可消耗B细胞，在其他自身免疫疾病中已显示出疗效。AIMS：在一项开放的、单中心的试点研究中，评估利妥昔单抗在难治性AIH患者中的安全性和有效性。方法：6名确诊的AIH患者，经强的松和硫唑嘌呤治疗失败，每两周注射两次利妥昔单抗1000 mg，并进行72周的随访。结果：利妥昔单抗耐受性良好，没有严重的不良事件。24周时，平均(+/-SD)天冬氨酸氨基转移酶水平明显改善(90.0+/-23.3U/L比31.3+/-4.2U/L；P=0.03)，平均免疫球蛋白G水平下降(16.4+/-2.0g/L比11.5+/-1.1g/L；P=0.056)。四名受试者中有三名停用了泼尼松剂量，一名受试者在停用类固醇后出现疼痛。在48周再次接受肝活检的所有四名受试者中，炎症分级均有所改善。FoxP3免疫组织化学检测的调节性T细胞水平与炎症活动平行，并且在后续的活检中没有增加。从基线到24周，血清趋化因子或细胞因子水平没有显著变化(n=5)，尽管干扰素-γ诱导的蛋白10水平在5个受试者中有3个改善。结论：利妥昔单抗是安全的，耐受性良好，并导致难治性AIH患者的生化改善。这些结果支持进一步研究利妥昔单抗作为治疗AIH的方法。
BACKGROUND: Although most patients with autoimmune hepatitis (AIH) respond to treatment with prednisone and/or azathioprine, some patients are intolerant or refractory to standard therapy. Rituximab is an anti-CD20 monoclonal antibody that depletes B cells and has demonstrated efficacy in other autoimmune conditions.AIMS: To evaluate the safety and efficacy of rituximab in patients with refractory AIH in an open-label, single-centre pilot study.METHODS: Six patients with definite, biopsy-proven AIH who failed prednisone and azathioprine treatment received two infusions of rituximab 1000 mg two weeks apart and were followed for 72 weeks.RESULTS: Rituximab was well tolerated with no serious adverse events. By week 24, mean (+/- SD) aspartate aminotransferase (AST) levels had significantly improved (90.0+/-23.3 U/L versus 31.3+/-4.2 U/L; P=0.03) and mean immunoglobulin G levels had fallen (16.4+/-2.0 g/L versus 11.5+/-1.1 g/L; P=0.056). The prednisone dose was weaned in three of four subjects, with one subject flaring after steroid withdrawal. Inflammation grade improved in all four subjects who underwent repeat liver biopsy at week 48. Regulatory T cell levels examined by FoxP3 immunohistochemistry paralleled inflammatory activity and did not increase on follow-up biopsies. There was no significant change in serum chemokine or cytokine levels from baseline to week 24 (n=5), although interferon-gamma-induced protein 10 levels improved in three of five subjects.CONCLUSIONS: Rituximab was safe, well tolerated and resulted in biochemical improvement in subjects with refractory AIH. These results support further investigation of rituximab as a treatment for AIH.