Institute of Clinical Neuroimmunology, Ludwig Maximilians University, D-81377 Munich, Germany.
Neurology. 2011 Apr 12;76(15):1310-5. doi: 10.1212/WNL.0b013e3182152881.
Neuromyelitis optica (NMO) is a severe autoimmune disease targeting optic nerves and spinal cord. The monoclonal anti-CD20 B-cell antibody rituximab is an emerging therapeutic option in NMO. However, neither long-term efficacy or safety of rituximab, nor the correlation between B-cell counts, B-cell fostering cytokines, aquaporin-4 antibodies (AQP4-ab), and disease activity in NMO, have been investigated prospectively.
We performed a prospective long-term cohort study of 10 patients with NMO who were treated up to 5 times with rituximab as a second-line therapy. Clinical examinations, B-cell counts, and serum concentrations of BAFF (B-cell activating factor of the TNF family; also called TNFSF13b), APRIL (a proliferation-inducing ligand; also called TNFSF13), AQP4-ab, and immunoglobulin levels were measured every 3 months.
Repeated treatment with rituximab led to sustained clinical stabilization in most patients with NMO. Disease activity correlated with B-cell depletion, but not clearly with AQP4-ab or levels of APRIL. BAFF levels increased after application of rituximab and indicated persisting efficacy of the drug but did not correlate with disease activity. Overall, rituximab was well-tolerated even after up to 5 consecutive treatment courses; however, we observed several severe adverse reactions.
Our data indicate that long-term therapy with rituximab is effective in NMO as a second-line therapy and has an acceptable safety profile. Retreatment with rituximab should be applied before reappearance of circulating B cells.
This study provides Class IV evidence that repeated doses of rituximab result in stabilization in most patients.
视神经脊髓炎（NMO）是一种针对视神经和脊髓的严重自身免疫性疾病。单克隆抗 CD20 B 细胞抗体利妥昔单抗是 NMO 的一种新兴治疗选择。然而，尚未前瞻性研究利妥昔单抗的长期疗效和安全性，以及 NMO 中 B 细胞计数、B 细胞滋养细胞因子、水通道蛋白-4 抗体（AQP4-ab）与疾病活动之间的相关性。
我们对 10 例 NMO 患者进行了前瞻性长期队列研究，这些患者接受了多达 5 次利妥昔单抗二线治疗。每 3 个月进行一次临床检查、B 细胞计数和血清 BAFF（肿瘤坏死因子家族的 B 细胞激活因子；也称为 TNFSF13b）、APRIL（增殖诱导配体；也称为 TNFSF13）、AQP4-ab 和免疫球蛋白水平的测定。
利妥昔单抗重复治疗可使大多数 NMO 患者的临床状况持续稳定。疾病活动与 B 细胞耗竭相关，但与 AQP4-ab 或 APRIL 水平不相关。利妥昔单抗应用后 BAFF 水平升高，表明药物持续有效，但与疾病活动无关。总体而言，利妥昔单抗即使在连续 5 个疗程后也具有良好的耐受性；然而，我们观察到了一些严重的不良反应。
我们的数据表明，利妥昔单抗作为二线治疗长期治疗 NMO 有效，且安全性良好。在循环 B 细胞再次出现之前，应重复利妥昔单抗治疗。
本研究提供了 IV 级证据，表明重复剂量的利妥昔单抗可使大多数患者的病情稳定。
