From the Department of Neurology (E.M., S.C., B.E., R.A.C.), Dell Medical School, University of Texas at Austin; Department of Neurology (L.S.), Stanford University School of Medicine, Palo Alto, CA; Division of Microbiology and Immunology (M.S.P.), Yerkes National Primate Research Center, and Department of Pathology and Laboratory Medicine, Emory University, Atlanta, GA; Department of Neurology and Program in Immunology (S.S.Z.), University of California San Francisco; and Departments of Neurology (E.M.F., T.C.F.), Ophthalmology & Neurosurgery, Dell Medical School at the University of Texas at Austin.
Neurol Neuroimmunol Neuroinflamm. 2020 Aug 7;7(6). doi: 10.1212/NXI.0000000000000868. Print 2020 Nov 5.
To determine whether the punctuated administration of low-dose rituximab, temporally linked to B-cell hyperrepopulation (defined when the return of CD19 B cells approximates 40%-50% of baseline levels as measured before alemtuzumab treatment inception), can mitigate alemtuzumab-associated secondary autoimmunity.
In this hypothesis-driven pilot study, 10 patients received low-dose rituximab (50-150 mg/m), a chimeric anti-CD20 monoclonal antibody, after either their first or second cycles of alemtuzumab. These patients were then routinely assessed for the development of autoimmune disorders and safety signals related to the use of dual monoclonal antibody therapy.
Five patients received at least 1 IV infusion of low-dose rituximab, following alemtuzumab therapy, with a mean follow-up of 41 months. None of the 5 patients developed secondary autoimmune disorders. An additional 5 patients with follow-up over less than 24 months received at least 1 infusion of low-dose rituximab treatment following alemtuzumab treatment. No secondary autoimmune diseases were observed.
An anti-CD20 "whack-a-mole" B-cell depletion strategy may serve to mitigate alemtuzumab-associated secondary autoimmunity in MS by reducing the imbalance in B- and T-cell regulatory networks during immune reconstitution. We believe that these observations warrant further investigation.
This study provides Class IV evidence that for people with MS, low-dose rituximab following alemtuzumab treatment decreases the risk of alemtuzumab-associated secondary autoimmune diseases.
确定低剂量利妥昔单抗的间歇性给药是否可以减轻阿仑单抗相关的继发性自身免疫。这种给药方式与 B 细胞过度增殖有关（当 CD19 B 细胞恢复到接近基线水平的 40%-50%时定义为 B 细胞过度增殖，该基线水平在阿仑单抗治疗开始前测量）。
在这项假设驱动的试点研究中，10 名患者在接受阿仑单抗治疗的第一或第二周期后，接受了低剂量利妥昔单抗（50-150mg/m）治疗，这是一种嵌合抗 CD20 单克隆抗体。然后，这些患者常规评估自身免疫性疾病的发展和与使用双单克隆抗体治疗相关的安全信号。
5 名患者在接受阿仑单抗治疗后至少接受了 1 次 IV 输注低剂量利妥昔单抗，平均随访 41 个月。这 5 名患者均未发生继发性自身免疫性疾病。另外 5 名随访时间少于 24 个月的患者在接受阿仑单抗治疗后至少接受了 1 次低剂量利妥昔单抗治疗。未观察到继发性自身免疫性疾病。
抗 CD20 的“打地鼠”B 细胞耗竭策略可能通过减少免疫重建期间 B 细胞和 T 细胞调节网络的失衡，从而减轻 MS 患者阿仑单抗相关的继发性自身免疫。我们认为这些观察结果值得进一步研究。
这项研究提供了 IV 级证据，表明对于多发性硬化症患者，阿仑单抗治疗后接受低剂量利妥昔单抗治疗可降低阿仑单抗相关继发性自身免疫性疾病的风险。
