Immune-reconstitution Inflammatory Syndrome in Multiple Sclerosis Patients Treated With Natalizumab: A Series of 4 Cases

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• 作者：Rosy N&rsquo ; gbo N&rsquo ; gbo Ikazabo ; MD¹ ; Christian Mostosi ; MD¹ ; Bé ; né ; dicte Quivron ; MD² ; Xavier Delberghe ; MD³ ; Kaoutar El Hafsi ; MS¹ ; Andreas P. Lysandropoulos ; MD¹ ; ^{andreas.lysandropoulos@erasme.ulb.ac.be" class="auth_mail" title="E-mail the corresponding author}
• 关键词：immune-reconstitution inflammatory syndrome ; JC virus ; multiple sclerosis ; natalizumab ; progressive multifocal leukoencephalopathy
• 刊名：Clinical Therapeutics
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：38
• 期：3
• 页码：670-675
• 全文大小：315 K

文摘

Natalizumab (NTZ) is an effective treatment for relapsing-remitting multiple sclerosis (RRMS). Progressive multifocal leukoencephalopathy (PML) is a rare complication of NTZ treatment. In patients developing PML, NTZ cessation causes a reconstruction of cellular immunity, a rapid transition of cells through the blood-brain barrier, and significant inflammation in the central nervous system, leading to immune-reconstitution inflammatory syndrome (IRIS), with potentially poor outcomes. The occurrence of this syndrome is accelerated by plasmapheresis, the standard treatment for NTZ-PML, due to enhanced clearance of NTZ and thus rapid reconstitution of cellular immunity. IRIS can also occur after cessation of NTZ in the absence of PML.

Methods

We describe 4 patients who developed IRIS after NTZ cessation.

Findings

For the first patient, treatment was switched to fingolimod to avoid risk of developing PML. Despite plasmapheresis, corticosteroids, and other therapies, the outcome in this patient was fatal. For the 3 other patients, PML was detected early on magnetic resonance imaging, and IRIS after NTZ cessation was managed with a favorable outcome; 1 of these patients was managed without plasmapheresis or corticosteroid treatment.

Implications

These cases demonstrate the need to consider and manage therapeutic strategies relative to the individual patient’s risk for PML or IRIS. NTZ cessation to avoid PML risk can lead to severe IRIS without PML. On the other hand, if PML develops and is detected early, plasmapheresis may not be considered necessary and IRIS may be limited, with a favorable outcome. These 2 scenarios should be considered when managing NTZ MS patients.