Aouba Achille, Pagnoux Christian, Bienvenu Boris, Mahr Alfred, Guillevin Loïc
Department of Internal Medicine and the French Vasculitis Study Group, Assistance Publique-Hôpitaux de Paris, Université Paris, 5-René-Descartes, Hôpital Cochin, 27, rue du faubourg Saint-Jacques, 75679, Paris Cedex 14, France.
Clin Rev Allergy Immunol. 2008 Feb;34(1):65-73. doi: 10.1007/s12016-007-8026-1. Epub 2007 Sep 12.
Available data on small numbers of patients with refractory and/or relapsing Wegener's granulomatosis support very good overall outcomes with rituximab, an anti-CD20 biotherapy targeting B cells, in combination with ongoing immunosuppressants, apparently independently of antineutrophil cytoplasm antibody (ANCA) status. However, clearly dissociated responses were observed, with constitutional and vasculitis-related symptoms often achieving complete responses within days or weeks, and granulomatous-related manifestations regressing more slowly over a few weeks to several months or not at all, particularly for orbital pseudotumors. Tolerance was good with few side effects, and when relapses occurred, more often after 12 months, a second or even a third rituximab cycle was almost always able to obtain another complete remission. Randomized trials are needed to define rituximab's best place, compared to cyclophosphamide, in initial and maintenance regimens; to determine optimally combined drugs, considering the various responses of granulomatous-related manifestations; and to delineate the role of circulating B-cell monitoring for pre-emptive management decisions. This promising biotherapy opens the way for other therapeutic agents targeting B lymphocytes and to improve our understanding of the pathophysiology of ANCA-associated vasculitis.
关于少数难治性和/或复发性韦格纳肉芽肿患者的现有数据表明，利妥昔单抗（一种靶向B细胞的抗CD20生物疗法）与持续使用的免疫抑制剂联合使用，总体疗效非常好，显然与抗中性粒细胞胞浆抗体（ANCA）状态无关。然而，观察到明显不同的反应，全身症状和与血管炎相关的症状通常在数天或数周内完全缓解，而与肉芽肿相关的表现则在数周至数月内消退得更慢，或根本不消退，特别是眼眶假瘤。耐受性良好，副作用很少，复发通常发生在12个月后，此时第二次甚至第三次利妥昔单抗治疗周期几乎总能再次获得完全缓解。需要进行随机试验，以确定与环磷酰胺相比，利妥昔单抗在初始和维持治疗方案中的最佳位置；考虑到与肉芽肿相关表现的不同反应，确定最佳联合用药；并阐明循环B细胞监测在预防性管理决策中的作用。这种有前景的生物疗法为其他靶向B淋巴细胞的治疗药物开辟了道路，并有助于提高我们对ANCA相关血管炎病理生理学的理解。
