三级神经免疫诊所的医源性中枢神经系统炎症的患病率。

Prevalence of iatrogenic CNS inflammation at a tertiary neuroimmunology clinic.

机构信息

Multiple Sclerosis and Neuroimmunology Program, University Hospitals Cleveland Medical Center, Cleveland, OH, USA; Case Western Reserve University School of Medicine, Cleveland, OH, USA; Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USA; University Hospitals Specialty Pharmacy, Cleveland, OH, USA; VA Multiple Sclerosis Center of Excellence, Cleveland VA Medical Center, Cleveland, OH, USA.

出版信息

J Neuroimmunol. 2022 Sep 15;370:577928. doi: 10.1016/j.jneuroim.2022.577928. Epub 2022 Jul 14.

DOI:10.1016/j.jneuroim.2022.577928

PMID:35853358

Abstract

BACKGROUND

Various vaccines, tumor-necrosis-factor-alpha inhibitors (TNFAIs), immune-checkpoint inhibitors (ICIs), and other immunomodulators have been linked to inflammatory CNS events. The prevalence of iatrogenic events in the neuroimmunology clinic is unknown.

OBJECTIVE

To evaluate the prevalence and clinical characteristics of iatrogenic CNS inflammation in a tertiary neuroimmunology clinic.

METHODS

We analyzed 422 consecutive patients seen over five years at a tertiary neuroimmunology clinic who were systematically screened for exposure to vaccines, TNFAIs, ICIs, or other immunomodulators. In patients with suspected iatrogenic events, the Naranjo Adverse Drug Reaction Probability Scale was used to score the probability of iatrogenicity.

RESULTS

In total, 27 potential iatrogenic events were observed, accounting for 6.4% of all new referrals. The average Naranjo score was 5.78 +/- 1.65 with 74% of the cases scored as probable and 26% scored as possible. The clinical phenotypes included MS relapses (37%); autoimmune encephalitis (30%); NMOSD attacks (15%); transverse myelitis (11%); optic neuritis (4%); and MOGAD attacks (4%). A monophasic course was observed in 44% of cases while 41% had a relapsing course. All patients stopped or interrupted treatment with the offending agent. In addition, 41% of the iatrogenic events were fully responsive to corticosteroids; 22% were partially responsive; and 15% resolved spontaneously. The most common potential triggers were vaccines (37%) followed by TNFAIs (33%) then ICIs (26%). A significantly higher number of probable iatrogenic events were observed among the ICI and vaccine groups compared to a higher number of possible events among the TNFAI group. The latter group also had a significantly longer interval since exposure. The ICI group was more likely to present with monophasic autoimmune encephalitis.

CONCLUSION

Iatrogenic CNS inflammation is rare and typically involves steroid-responsive monophasic events. A subset of iatrogenic events can unmask or worsen relapsing disorders. The probability of iatrogenicity was higher in vaccine and ICI-related events compared to TNFAI-related events.

摘要

背景

各种疫苗、肿瘤坏死因子-α 抑制剂（TNFAIs）、免疫检查点抑制剂（ICIs）和其他免疫调节剂与中枢神经系统炎症性事件有关。神经免疫诊所中医源性事件的发生率尚不清楚。

目的

评估三级神经免疫诊所中医源性中枢神经系统炎症的发生率和临床特征。

方法

我们分析了在三级神经免疫诊所就诊的 422 例连续患者，对其进行了系统的疫苗、TNFAIs、ICIs 或其他免疫调节剂暴露筛查。在疑似医源性事件的患者中，使用 Naranjo 药物不良反应概率量表评估医源性的可能性。

结果

共观察到 27 例潜在的医源性事件，占所有新就诊患者的 6.4%。平均 Naranjo 评分为 5.78 +/- 1.65，74%的病例评为可能，26%评为很可能。临床表型包括 MS 复发（37%）；自身免疫性脑炎（30%）；NMOSD 发作（15%）；横贯性脊髓炎（11%）；视神经炎（4%）；MOGAD 发作（4%）。44%的病例表现为单相病程，41%为复发病程。所有患者均停止或中断了致病药物的治疗。此外，41%的医源性事件对皮质类固醇完全有效；22%部分有效；15%自发缓解。最常见的潜在触发因素是疫苗（37%），其次是 TNFAIs（33%），然后是 ICIs（26%）。ICI 组和疫苗组观察到的可能性医源性事件明显更多，而 TNFAI 组观察到的可能性事件更多。后者组暴露后时间间隔也明显更长。ICI 组更有可能表现为单相自身免疫性脑炎。