Specks U, Fervenza F C, McDonald T J, Hogan M C
Division of Pulmonary and Critical Care Medicine, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
Arthritis Rheum. 2001 Dec;44(12):2836-40. doi: 10.1002/1529-0131(200112)44:12<2836::aid-art471>3.0.co;2-w.
We report on the successful, compassionate use of the anti-CD20 chimeric monoclonal antibody rituximab in a patient with chronic, relapsing cytoplasmic antineutrophil cytoplasmic antibody (cANCA)-associated Wegener's granulomatosis (WG). The patient initially responded to treatment with glucocorticoids and cyclophosphamide. However, bone marrow toxicity during cyclophosphamide treatment of a relapse precluded its further use. Azathioprine and mycophenolate mofetil treatment had failed to maintain remission of the WG, and methotrexate was contraindicated. Because the patient's 5-year course was characterized by close correlation of cANCA levels with disease activity, selective elimination of cANCA was deemed a treatment option for his latest relapse. He was given 4 infusions of 375 mg/M2 of rituximab and high-dose glucocorticoids. Complete remission was associated with the disappearance of B lymphocytes and cANCA. Glucocorticoid treatment was then discontinued. After 11 months, the cANCA recurred, and rituximab therapy was repeated, without glucocorticoids. At 8 months after the second course of rituximab (18 months after the first course), the patient's WG has remained in complete remission. Elimination of B cells by rituximab therapy may prove to be an effective and safe new treatment modality for ANCA-associated vasculitis and possibly other autoimmune diseases. This modality warrants closer examination in a carefully conducted clinical trial.
我们报告了抗CD20嵌合单克隆抗体利妥昔单抗在一名患有慢性复发性胞浆抗中性粒细胞胞浆抗体（cANCA）相关韦格纳肉芽肿（WG）患者中的成功且人道的应用。该患者最初对糖皮质激素和环磷酰胺治疗有反应。然而，环磷酰胺治疗复发时出现的骨髓毒性使其无法继续使用。硫唑嘌呤和霉酚酸酯治疗未能维持WG的缓解，且甲氨蝶呤禁用。由于该患者5年病程的特点是cANCA水平与疾病活动密切相关，选择性清除cANCA被认为是其最近一次复发的一种治疗选择。他接受了4次375 mg/M2的利妥昔单抗输注和高剂量糖皮质激素治疗。完全缓解与B淋巴细胞和cANCA的消失相关。随后停用了糖皮质激素治疗。11个月后，cANCA复发，再次进行利妥昔单抗治疗，未使用糖皮质激素。在第二疗程利妥昔单抗治疗8个月后（第一疗程后18个月），患者的WG仍处于完全缓解状态。利妥昔单抗治疗清除B细胞可能被证明是ANCA相关血管炎以及可能其他自身免疫性疾病的一种有效且安全的新治疗方式。这种方式值得在精心开展的临床试验中进行更深入的研究。
