TNFα 抑制剂暴露后的中枢神经系统脱髓鞘：一项回顾性队列研究。
CNS demyelination with TNFα inhibitor exposure: A retrospective cohort study.
机构信息
Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
出版信息
J Neuroimmunol. 2021 Jul 15;356:577587. doi: 10.1016/j.jneuroim.2021.577587. Epub 2021 Apr 26.
OBJECTIVE
To study long-term outcomes in patients with CNS demyelinating events exposed to TNFa-inhibitors (TNFai), including subsequent clinical relapse, MRI lesions, and use of disease modifying therapy (DMT) for MS.
METHODS
Adult patients evaluated for a CNS demyelinating disease during TNFai use were identified at Mass General Brigham [01/1998-08/2020] and analyzed in clinically-relevant subgroups. Inclusion criteria required a first neurological event while taking a TNFai, MRI lesions consistent with demyelination, and the absence of a more probable alternative diagnosis.
RESULTS
21 cases (mean age 44 years, 20 female, 14 ≥ 2 MS risk factors) had an index neurological event (INE) at a median of 12 months (range 1-176) from onset of TNFai use (adalimumab in 10, etanercept 6, infliximab 5). MRI lesions were most often present in periventricular (16/20, 80%) and spinal zones (10/20, 50%); 37% (7/19) met ≥ 2 Barkhof criteria at onset. CSF testing was abnormal in 64% (7/11). 67% (10/15) with available follow-up MRIs developed new lesions by a median of 29.5 months of MRI surveillance (median MRI surveillance 60 months); 55% (11/20) met ≥ 2 Barkhof criteria. 47% (8/17) suffered a clinical relapse by a median of 40.5 months of clinic follow-up (median clinic follow-up since INE: 26 months). In patients discontinuing TNFai (18/21, 86%) at INE onset, 56% (10/18) had further evidence of CNS demyelination. Six patients (6/21, 29%) started an MS disease modifying therapy (DMT) at INE of whom 50% (3/6) had subsequent disease activity. Continuing or restarting TNFai was followed by relapse in 75% (3/4). 65% (13/20) met 2017 McDonald criteria for MS at INE with another 10% (15/20, 75%) by study conclusion.
CONCLUSIONS
With extended follow-up, a majority of patients had a relapsing CNS demyelinating disorder-as evidenced by new MRI lesions or clinical relapses-despite TNFai discontinuation.
目的
研究接受 TNFa 抑制剂（TNFai）治疗的中枢神经系统脱髓鞘事件患者的长期预后，包括随后的临床复发、MRI 病变和多发性硬化症的疾病修正治疗（DMT）的使用。
方法
在马萨诸塞州综合医院（Mass General Brigham）[1998 年 1 月至 2020 年 8 月]确定了在 TNFai 治疗期间接受中枢神经系统脱髓鞘疾病评估的成年患者，并在临床相关亚组中进行了分析。纳入标准要求在接受 TNFai 治疗期间出现首次神经事件、MRI 病变与脱髓鞘一致，且无更可能的替代诊断。
结果
21 例（平均年龄 44 岁，20 例女性，14 例≥2 个 MS 危险因素）在 TNFai 使用开始后中位时间 12 个月（范围 1-176）出现索引性神经事件（INE）（阿达木单抗 10 例，依那西普 6 例，英夫利昔单抗 5 例）。MRI 病变最常位于脑室周围（20 例中有 16 例，80%）和脊髓区（20 例中有 10 例，50%）；37%（19 例中有 7 例）在发病时符合≥2 项 Barkhof 标准。64%（11 例中有 7 例）的脑脊液检查异常。在中位 MRI 监测 29.5 个月（中位 MRI 监测 60 个月）时，67%（15 例中有 10 例）出现新的 MRI 病变；55%（20 例中有 11 例）符合≥2 项 Barkhof 标准。在中位临床随访 40.5 个月（自 INE 起的中位临床随访时间：26 个月）时，47%（17 例中有 8 例）发生临床复发。在 INE 发病时停用 TNFai（18/21，86%）的 18 例患者中，56%（18 例中有 10 例）有进一步的中枢神经系统脱髓鞘证据。6 名患者（21 例中有 6 例，29%）在 INE 时开始使用多发性硬化症疾病修正治疗（DMT），其中 50%（6 例中有 3 例）随后出现疾病活动。继续或重新开始 TNFai 后，75%（4 例中有 3 例）出现复发。65%（20 例中有 13 例）在 INE 时符合 2017 年 McDonald 多发性硬化症标准，另有 10%（20 例中有 15 例，75%）在研究结束时符合标准。
结论
尽管停用了 TNFai，但大多数患者仍存在复发性中枢神经系统脱髓鞘疾病，表现为新的 MRI 病变或临床复发，这在延长随访后得到了证实。
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