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. 2019 May:30:136-140.
doi: 10.1016/j.msard.2019.02.013. Epub 2019 Feb 11.

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

Pavan Bhargava  1 , Cassie Wicken  2 , Matthew D Smith  2 , Roy E Strowd  2 , Irene Cortese  3 , Daniel S Reich  3 , Peter A Calabresi  2 , Ellen M Mowry  2
Affiliations

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

Pavan Bhargava et al. Mult Scler Relat Disord. 2019 May.

Abstract

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.

Keywords: Clinical trial; Intrathecal rituximab; Leptomeningeal inflammation; Progressive multiple sclerosis.

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Figures

Figure 1.
Figure 1.. Trial design and the effect of IT rituximab on B cell populations and biomarkers in CSF
The design of the trial is depicted in panel A; timeline is in weeks. Panel B depicts three examples of leptomeningeal contrast enhancing lesions noted in participants in the trial (yellow arrows). Panel C shows change in peripheral B cell counts over the course of the trial (individual participant data in gray, median across participants in red), while panel D shows CSF B cell counts. We also assessed change in CSF levels of markers of various immune cell populations: E (sCD27), F (sCD21), and G (sCD14). The changes in CSF levels of cytokines/chemokines are depicted in panel H (BAFF), I (CXCL-13), J (CCL-19), and K (CCL-21). Lastly, we measured levels of neurofilament-light chain (NfL) in the CSF (panel L). Comparisons were made with either paired t-test or Wilcoxon sign rank test. * p<0.05
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