Author Of 1 Presentation
P0881 - “Mild disease course of carry-over progressive multifocal leukoencephalopathy after switching from natalizumab to ocrelizumab” (ID 1406)
Abstract
Background
Natalizumab is an effective disease modifying therapy (DMT) for relapsing remitting multiple sclerosis (RRMS). However, it is associated with an increased risk of progressive multifocal leukoencephalopathy (PML). Nine confirmed cases of PML have been reported in patients using ocrelizumab, another effective DMT for MS. In 8 cases, patients previously used natalizumab or fingolimod, likely causing PML. This phenomenon has been described as carry-over PML.
Objectives
To describe the disease course of carry-over PML after switching from natalizumab to ocrelizumab in two patients with RRMS.
Methods
Two case reports with 1 year of follow-up and retrospective longitudinal measurements of serum neurofilament light (sNfL) levels and B-cell count. Both patients provided informed consent.
Results
Regular follow-up showed no disease activity under natalizumab treatment and both patients switched to ocrelizumab following a stringent safety protocol including two additional MRI brain scans and cerebrospinal fluid (CSF) analysis. Both patients received a single infusion of 300 mg ocrelizumab before PML diagnosis. PML was diagnosed ±11 weeks (case 1) and ±13 weeks (case 2) after the last natalizumab infusion. At that time, both patients were asymptomatic. In retrospect, subtle signs suggestive of PML were already present on MRI under natalizumab treatment. One patient developed PML despite extended interval dosing of natalizumab. Both patients developed mild immune reconstitution inflammatory syndrome (IRIS) despite complete B-cell depletion. SNfL levels were 9.9 pg/ml (reference range 1-15 pg/ml) for case 1 and 16.7 pg/ml (reference range 2-18 pg/ml) for case 2 at the time of PML diagnosis and increased to 15.0 pg/ml and 36.5 pg/mL during PML-IRIS. SNfL was not elevated before radiological diagnosis of PML. PML-IRIS lesions stabilized after treatment with mefloquine and mirtazapine followed by methylprednisolone with sNfL levels of 9.0 pg/mL and 12.3 pg/mL, respectively. One patient reported no clinical symptoms and one patient only mild clinical symptoms with full recovery during the disease course of PML-IRIS. Both patients continued with ocrelizumab when B-cells started to repopulate ±10 months after the first ocrelizumab infusion.
Conclusions
The clinical course of carry-over PML was mild in both patients, suggesting that B-cell depletion did not aggravate PML-IRIS in these two patients.