Stasi R, Stipa E, Del Poeta G, Amadori S, Newland A C, Provan D
Department of Medical Sciences, Regina Apostolorum Hospital, Via San Francesco, 50, 00041 Albano Laziale, Italy.
Rheumatology (Oxford). 2006 Nov;45(11):1432-6. doi: 10.1093/rheumatology/kel098. Epub 2006 Apr 21.
Rituximab, a chimeric anti-CD20 monoclonal antibody, has been shown to be quite effective in the treatment of immune disorders resulting from autoantibodies. We prospectively studied the long-term effects of rituximab in 10 patients with anti-neutrophil cytoplasmic antibody (ANCA)-positive vasculitis refractory to conventional therapy (n=3) or in second or subsequent relapse (n=7).
The median age of patients was 53 yrs (range 38-70 yrs). Eight were classified as Wegener's granulomatosis, and two as microscopic polyangiitis. Clinical activity was assessed using the Birmingham Vasculitis Activity Score modification for Wegener's granulomatosis. Treatment consisted of intravenous infusions of rituximab given at the dose of 375 mg/m2 weekly for four consecutive weeks.
All patients experienced a rapid clinical improvement following the administration of rituximab, with nine complete responses and one partial response at 6 months. With a median follow-up of 33.5 months (range 26-45 months), three patients have thus far relapsed. Retreatment with the monoclonal antibody at the same dose and schedule resulted in a new sustained response in all these patients. Rituximab therapy resulted in prolonged B-cell depletion. The ANCA titres decreased significantly in all patients, with eight out of 10 becoming ANCA-negative and three remaining ANCA-negative even after B-cell recovery. Infusion-related side effects were observed in one patient, but were of mild intensity and did not require discontinuation of treatment.
Rituximab is an effective and well-tolerated treatment for patients with ANCA-associated vasculitis and should be strongly considered in severely affected patients who do not respond to standard therapy or in those in whom cytotoxic therapy bears a high risk of morbidity.
利妥昔单抗是一种嵌合抗CD20单克隆抗体，已被证明在治疗自身抗体引起的免疫紊乱方面相当有效。我们前瞻性地研究了利妥昔单抗对10例抗中性粒细胞胞浆抗体（ANCA）阳性血管炎患者的长期疗效，这些患者对传统治疗无效（3例）或处于第二次或后续复发阶段（7例）。
患者的中位年龄为53岁（范围38 - 70岁）。8例被归类为韦格纳肉芽肿，2例为显微镜下多血管炎。使用针对韦格纳肉芽肿的伯明翰血管炎活动评分修正版评估临床活动度。治疗包括静脉输注利妥昔单抗，剂量为375 mg/m²，每周一次，连续四周。
所有患者在给予利妥昔单抗后临床迅速改善，6个月时9例完全缓解，1例部分缓解。中位随访33.5个月（范围26 - 45个月），截至目前有3例患者复发。用相同剂量和方案再次使用单克隆抗体治疗后，所有这些患者均获得了新的持续缓解。利妥昔单抗治疗导致B细胞长期耗竭。所有患者的ANCA滴度均显著下降，10例中有8例变为ANCA阴性，3例即使在B细胞恢复后仍保持ANCA阴性。1例患者观察到与输注相关的副作用，但程度较轻，无需中断治疗。
利妥昔单抗是治疗ANCA相关血管炎患者的一种有效且耐受性良好的治疗方法，对于对标准治疗无反应或细胞毒性治疗有高发病风险的重症患者应强烈考虑使用。
