Effect of treatment with interferon beta-1a on changes in voxel-wise magnetization transfer ratio in normal appearing brain tissue and lesions of patients with relapsing-remitting multiple sclerosis: a 24-week, controlled pilot study

PLoS One. 2014 Mar 13;9(3):e91098. doi: 10.1371/journal.pone.0091098. eCollection 2014.

Abstract

Background: This pilot study investigated changes in remyelinating and demyelinating activity in normal appearing brain tissue (NABT) and lesions, by using voxel-wise magnetization transfer ratio (VW-MTR), in patients with relapsing-remitting multiple sclerosis (RRMS) receiving interferon beta-1a 44 mcg subcutaneously (IFN β-1a SC) three times weekly versus healthy controls (HCs) (NCT01085318).

Methods: Increasing (suggestive of remyelination) and decreasing (suggestive of demyelination) VW-MTR changes in NABT and in T2, T1 and gadolinium (Gd)-enhancing lesion volume were measured over 24 weeks in 23 patients treated with IFN β-1a SC and in 15 HCs (where applicable). VW-MTR changes were tested using the Wilcoxon signed-rank or Wilcoxon rank-sum test.

Results: A trend for greater volume of NABT with increasing VW-MTR at 24 weeks was observed for patients versus HCs (median [range] 1206 [0-15278]; 342 [0-951] mm3; p = 0.061). NABT volume with increasing VW-MTR at 12 weeks was significantly greater in patients than in HCs (852 [6-11577]; 360 [0-1755] mm3; p = 0.028). Similar findings were detected for lesion volumes. Two patients with notably high numbers of Gd-enhancing lesions at baseline had a markedly greater volume of tissue with increasing VW-MTR compared with other patients. Volume of NABT tissue with decreasing VW-MTR was significantly greater in patients versus HCs at 24 weeks (942 [0-6141]; 297 [0-852] mm3; p<0.001).

Conclusions: The significant change in NABT volume with increasing VW-MTR at 12 weeks suggests that active remyelination in patients with RRMS may occur during treatment with IFN β-1a SC. Findings from two patients with the highest number of Gd-enhancing lesions at baseline suggest that extensive remyelination in NABT may occur in patients with high disease activity. Tissue volume with decreasing VW-MTR was greater in patients than in HCs, despite treatment, validating the sensitivity of this technique for detecting MS disease activity.

Trial registration: ClinicalTrials.gov NCT01085318.

Publication types

  • Clinical Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brain / drug effects
  • Brain / pathology*
  • Female
  • Humans
  • Interferon beta-1a / therapeutic use*
  • Magnetic Resonance Imaging
  • Magnetics
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Multiple Sclerosis, Relapsing-Remitting / pathology*
  • Myelin Sheath / metabolism
  • Pilot Projects
  • Treatment Outcome

Substances

  • Interferon beta-1a

Associated data

  • ClinicalTrials.gov/NCT01085318

Grants and funding

This study was sponsored by EMD Serono, Inc., Rockland, MA (www.emdserono.com/), a subsidiary of Merck KGaA, Darmstadt, Germany, and by Pfizer, Inc, New York, NY (www.pfizer.com/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Esther Law and Chris Grantham of Caudex Medical, who assisted in preparing the initial draft of the manuscript, collating the comments of authors and other named contributors, as well as assembling tables and figures, were supported by EMD Serono, Inc., a subsidiary of Merck KGaA, Darmstadt, Germany.