Trial of intrathecal rituximab in progressive multiple sclerosis patients with evidence of leptomeningeal contrast enhancement

Background: Leptomeningeal inflammation is associated with increased cortical damage and worse clinical outcomes in MS. It may be detected on contrast-enhanced T2-FLAIR imaging as focal leptomeningeal contrast-enhancement (LME). Objective: To assess the safety of intrathecal (IT) rituximab in progressive MS (PMS) and to assess its effects on LME and CSF biomarkers. Methods: PMS patients had a screening MRI to detect LME. Participants satisfying eligibility criteria underwent two IT administrations of 25 mg rituximab 2 weeks apart. Follow-up lumbar puncture and MRI were performed at 8 and 24 weeks after the first treatment. Results: Of 36 patients screened 15 had LME, 11 consented, and 8 received study treatment. Mean age was 56.7 years and number of LME lesions ranged from 1 to 3. No serious adverse effects occurred. We noted profound reductions in peripheral B cells from baseline to week 2 and 8 with some return at week 24. We also observed transient reductions in CSF B cells and CXCL-13 levels with an increase in BAFF levels. However, the number of LME did not change following treatment. Conclusions: IT rituximab was well tolerated in PMS patients and had transient effects on CSF biomarkers but did not change LME.