Neurology, Neurophysiology and Neurobiology Unit, Department of Medicine, Università Campus Bio-Medico di Roma, Rome, Italy.
Neurology, Neurophysiology and Neurobiology Unit, Department of Medicine, Università Campus Bio-Medico di Roma, Rome, Italy.
Mult Scler Relat Disord. 2021 Feb;48:102734. doi: 10.1016/j.msard.2020.102734. Epub 2021 Jan 2.
. Teriflunomide is an immunomodulatory drug approved for Multiple Sclerosis (MS) treatment that inhibits dihydroorotate dehydrogenase, a mitochondrial enzyme involved in the de novo pyrimidine synthesis pathway. This mechanism can produce antiviral effects, thus teriflunomide has gained attention during COVID-19 pandemic. Moreover, in the last months, some case-reports have been published describing MS patients treated with teriflunomide who developed mild and self-limiting forms of COVID-19.
Here, we describe the case of a 57-year-old man affected by MS, and treated with teriflunomide, who developed a mild form of SARS-CoV-2 infection. Moreover, we provide a detailed literature review about the available cases of COVID-19 in MS patients treated with teriflunomide. We report clinical features, disease course and outcome, and we discuss similarities and differences among patients.
Apart from the present report, since February 2020, five papers have been published describing 14 MS patients who developed SARS-CoV-2 infection during teriflunomide treatment. Patients were mostly female (53%), with an average age of 50.5 (±11.3) years. Median EDSS was 2.25 (range 0-6). The average time on treatment with teriflunomide was 3.7 (± 1.6) years. Relevant comorbidities were present in 4 patients (27%). Regarding SARS-CoV-2 infection, the most common symptom was fever (100%) followed by gastrointestinal disturbances (67%), fatigue (55%) and cough (55%). 5 patients were hospitalized and 2 required oxygen support. In patient hospitalized (n=5) compared to the others (n=10), age was significantly higher (59.6 vs 45.9 years, p=0.025) while gender, EDSS, duration of teriflunomide therapy and comorbidities were not significantly different. Outcome was good for all patients with a variable recovery time, ranging from few days to some weeks. Teriflunomide was continued during the entire course of SARS-CoV-2 infection in all patients except for two. Compared to the patients already described, our patient was 7 years older, average time on teriflunomide treatment was about 2.5 years shorter, and median EDSS was 1.5 point lower. Despite significant comorbidities, the outcome was good since our patient was hospitalized but he did not require oxygen supplementation nor intensive care and was able to return at home after only 10 days. Teriflunomide therapy was continued throughout the period.
Available data suggest that teriflunomide therapy should not be discontinued in MS patients who develop SARS-CoV-2 infection, also in presence of significant comorbidities or clinical conditions requiring hospitalization. Additional studies are necessary to assess if the drug can also have a protective role against SARS-CoV-2.
特立氟胺是一种免疫调节药物，已被批准用于多发性硬化症（MS）的治疗，可抑制二氢乳清酸脱氢酶，这是一种参与从头嘧啶合成途径的线粒体酶。这种机制可以产生抗病毒作用，因此特立氟胺在 COVID-19 大流行期间引起了关注。此外，在过去的几个月中，已经发表了一些病例报告，描述了接受特立氟胺治疗的 MS 患者出现了 COVID-19 的轻度和自限性形式。
在这里，我们描述了一名 57 岁男性的病例，该患者患有 MS，接受了特立氟胺治疗，出现了 SARS-CoV-2 感染的轻度形式。此外，我们还提供了关于接受特立氟胺治疗的 MS 患者中 COVID-19 的现有病例的详细文献综述。我们报告了临床特征、疾病过程和结果，并讨论了患者之间的相似点和不同点。
除了本报告外，自 2020 年 2 月以来，已经发表了五篇描述了 14 名在接受特立氟胺治疗期间感染 SARS-CoV-2 的 MS 患者的论文。患者主要为女性（53%），平均年龄为 50.5（±11.3）岁。平均 EDSS 为 2.25（范围 0-6）。接受特立氟胺治疗的平均时间为 3.7（±1.6）年。4 名患者存在相关合并症（27%）。关于 SARS-CoV-2 感染，最常见的症状是发热（100%），其次是胃肠道紊乱（67%）、疲劳（55%）和咳嗽（55%）。5 名患者住院，2 名需要吸氧支持。在住院患者（n=5）与其他患者（n=10）相比，年龄明显更高（59.6 岁比 45.9 岁，p=0.025），而性别、EDSS、特立氟胺治疗持续时间和合并症无明显差异。所有患者的结局均良好，恢复时间不等，从数天到数周不等。除了两名患者外，所有患者在整个 SARS-CoV-2 感染期间都继续接受特立氟胺治疗。与已经描述的患者相比，我们的患者年龄大了 7 岁，接受特立氟胺治疗的平均时间缩短了约 2.5 年，EDSS 中位数低了 1.5 分。尽管存在显著的合并症，但由于我们的患者住院但不需要补充氧气或重症监护，并且仅 10 天后就能回家，因此结局良好。特立氟胺治疗在整个期间都在继续。
现有数据表明，在患有 SARS-CoV-2 感染的 MS 患者中，即使存在显著合并症或需要住院治疗的临床情况，也不应停止特立氟胺治疗。需要进一步的研究来评估该药物是否也具有预防 SARS-CoV-2 的作用。
