Purpose: 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.
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Article Synopsis
- Natalizumab (NTZ) is an effective treatment for active relapsing-remitting multiple sclerosis (MS), but many patients experience reactivation of the disease after stopping treatment.
- A study analyzed 89 patients from four Finnish hospitals to identify risk factors for reactivation within 12 months after discontinuing NTZ, using criteria such as prior relapse frequency and disability status.
- Results indicated that patients with more relapses before starting NTZ and higher disability scores were more likely to have reactivation, while subsequent treatments did not prevent relapses, particularly when there was a longer washout period after NTZ.
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