Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden / Center for Molecular Medicine, Karolinska University Hospital Solna, Stockholm, Sweden.
Immune Regulation Laboratory, Institute for Research in Biomedicine, Bellinzona, Switzerland.
Mult Scler. 2018 Aug;24(9):1224-1233. doi: 10.1177/1352458517720044. Epub 2017 Aug 1.
Rituximab is a chimeric monoclonal anti-CD20 B-cell-depleting antibody increasingly used off-label in multiple sclerosis (MS). The clinical relevance of anti-drug antibodies (ADAs) against rituximab in MS is unknown.
To determine frequency of ADA in relation to B-cell counts, allergic reactions and clinical efficacy in a large cohort of MS-treated patients.
Cross-sectional study with collection of serum samples from 339 MS patients immediately before a scheduled rituximab infusion. ADAs were detected using an in-house-validated electrochemiluminescent immunoassay and a commercial enzyme-linked immunosorbent assay (ELISA) to compare methods. Data on patient demographics and clinical outcomes were retrieved from the Swedish MS Registry and patient records.
ADAs were detected in 37% of relapsing-remitting MS and 26% in progressive forms of MS. Presence of ADAs decreased with increasing number of rituximab infusions. There was a significant association between both presence and titres of ADAs and incomplete B-cell depletion, but not with infusion/adverse reactions or clinical outcomes at the group level. Only five patients terminated rituximab during follow-up, four of which were ADA positive.
Rituximab treatment is associated with a high degree of ADAs, which correlates with efficacy of B-cell depletion; however, the clinical relevance of ADAs remains uncertain.
利妥昔单抗是一种嵌合型单克隆抗 CD20 B 细胞耗竭抗体，在多发性硬化症（MS）中越来越多地被超适应证使用。抗药物抗体（ADAs）在 MS 中对抗利妥昔单抗的临床相关性尚不清楚。
在大量接受 MS 治疗的患者中，确定 ADA 与 B 细胞计数、过敏反应和临床疗效的关系。
这是一项横断面研究，收集了 339 名 MS 患者在预定的利妥昔单抗输注前的血清样本。使用内部验证的电化学发光免疫分析和商业酶联免疫吸附试验（ELISA）检测 ADAs，以比较方法。从瑞典 MS 登记处和患者记录中检索患者人口统计学和临床结局的数据。
在复发缓解型 MS 中，ADA 的检出率为 37%，在进行性 MS 中为 26%。ADA 的存在随利妥昔单抗输注次数的增加而减少。ADA 的存在和滴度与不完全 B 细胞耗竭之间存在显著关联，但与输注/不良反应或组水平的临床结局无关。在随访期间，只有 5 名患者停止使用利妥昔单抗，其中 4 名 ADA 阳性。
利妥昔单抗治疗与高度的 ADA 相关，这与 B 细胞耗竭的疗效相关；然而，ADA 的临床相关性仍不确定。
