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利妥昔单抗联合或不联合聚乙二醇化干扰素α-2b加利巴韦林治疗严重丙型肝炎病毒相关性血管炎的疗效和耐受性:32例患者的长期随访研究

Efficacy and tolerability of rituximab with or without PEGylated interferon alfa-2b plus ribavirin in severe hepatitis C virus-related vasculitis: a long-term followup study of thirty-two patients.

作者信息

Terrier Benjamin, Saadoun David, Sène Damien, Sellam Jérémie, Pérard Laurent, Coppéré Brigitte, Karras Alexandre, Blanc François, Buchler Matthias, Plaisier Emmanuelle, Ghillani Pascale, Rosenzwajg Michelle, Cacoub Patrice

机构信息

Department of Internal Medicine, Groupe Hospitalier Pitié-Salpétrière, Assistance Publique-Hôpitaux de Paris (AP-HP), CNRS UMR 7211, and Université Pierre et Marie Curie Paris 6, Paris, France.

出版信息

Arthritis Rheum. 2009 Aug;60(8):2531-40. doi: 10.1002/art.24703.

DOI:10.1002/art.24703
PMID:19644879
Abstract

OBJECTIVE

To report on the long-term followup of a cohort of patients with hepatitis C virus (HCV)-related vasculitis treated with rituximab with or without PEGylated interferon alfa-2b (PEG-IFN alfa-2b) plus ribavirin.

METHODS

The study group comprised 32 HCV RNA-positive patients with HCV-related vasculitis: 20 patients were treated with rituximab and PEG-IFN alfa-2b (9 of whom had not previously received antiviral treatment and 11 of whom had experienced disease resistance to or relapse with antiviral treatment), and 12 antiviral-intolerant patients were treated with rituximab alone.

RESULTS

Treatment with rituximab and PEG-IFN alfa-2b plus ribavirin induced a complete clinical response and a partial clinical response in 80% and 15% of patients, respectively, a complete immunologic response and a partial immunologic response in 67% and 33% of patients, respectively, and a sustained virologic response in 55% of patients. Treatment with rituximab alone induced a complete clinical response and a partial clinical response in 58% and 9% of patients, respectively, and a complete immunologic response and a partial immunologic response in 46% and 36% of patients, respectively. B cell depletion was achieved in 96% of patients, and B cell recovery began after a median delay of 12 months. After a mean+/-SD followup period of 23+/-12 months, 22% of patients experienced a clinical relapse, and 34% of patients experienced an immunologic relapse. All relapses were associated with the absence of virologic control, and 78% of relapses were associated with B cell recovery. Six patients were re-treated with rituximab. All 6 of these patients had a complete clinical response, 50% had a complete immunologic response, and 50% had a partial immunologic response. Rituximab was well tolerated overall.

CONCLUSION

Rituximab is an effective treatment of severe and/or refractory HCV-related vasculitis. Relapses were consistently associated with the absence of virologic control. The clinical and immunologic efficacy of rituximab after repeated infusion appeared to be the same as that observed after induction therapy.

摘要

目的

报告一组丙型肝炎病毒(HCV)相关血管炎患者接受利妥昔单抗联合或不联合聚乙二醇化干扰素α-2b(PEG-IFNα-2b)加利巴韦林治疗的长期随访情况。

方法

研究组包括32例HCV RNA阳性的HCV相关血管炎患者:20例患者接受利妥昔单抗和PEG-IFNα-2b治疗(其中9例此前未接受过抗病毒治疗,11例曾对抗病毒治疗耐药或复发),12例对抗病毒治疗不耐受的患者仅接受利妥昔单抗治疗。

结果

利妥昔单抗联合PEG-IFNα-2b加利巴韦林治疗分别使80%和15%的患者获得完全临床缓解和部分临床缓解,分别使67%和33%的患者获得完全免疫缓解和部分免疫缓解,55%的患者获得持续病毒学缓解。仅用利妥昔单抗治疗分别使58%和9%的患者获得完全临床缓解和部分临床缓解,分别使46%和36%的患者获得完全免疫缓解和部分免疫缓解。96%的患者实现了B细胞耗竭,B细胞恢复的中位延迟时间为12个月。在平均±标准差为23±12个月的随访期后,22%的患者出现临床复发,34%的患者出现免疫复发。所有复发均与病毒学未得到控制有关,78%的复发与B细胞恢复有关。6例患者接受了利妥昔单抗再治疗。所有6例患者均获得完全临床缓解,50%获得完全免疫缓解,50%获得部分免疫缓解。利妥昔单抗总体耐受性良好。

结论

利妥昔单抗是治疗严重和/或难治性HCV相关血管炎的有效方法。复发始终与病毒学未得到控制有关。重复输注后利妥昔单抗的临床和免疫疗效似乎与诱导治疗后观察到的疗效相同。

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