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

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

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.

MeSH terms

  • Antigens, CD / cerebrospinal fluid
  • B-Lymphocytes / pathology
  • Cytokines / cerebrospinal fluid
  • Disability Evaluation
  • Female
  • Follow-Up Studies
  • Humans
  • Immunologic Factors / therapeutic use*
  • Injections, Spinal
  • Magnetic Resonance Imaging
  • Male
  • Meninges / diagnostic imaging
  • Meninges / pathology*
  • Middle Aged
  • Multiple Sclerosis, Chronic Progressive / cerebrospinal fluid
  • Multiple Sclerosis, Chronic Progressive / diagnostic imaging
  • Multiple Sclerosis, Chronic Progressive / drug therapy*
  • Multiple Sclerosis, Chronic Progressive / pathology*
  • Organic Chemicals / cerebrospinal fluid
  • Rituximab / therapeutic use*
  • Statistics, Nonparametric
  • Treatment Outcome

Substances

  • Antigens, CD
  • Cytokines
  • Immunologic Factors
  • Organic Chemicals
  • Rituximab
  • kretazine