The Effect of Three Times a Week Glatiramer Acetate on Cerebral T1 Hypointense Lesions in Relapsing-Remitting Multiple Sclerosis

J Neuroimaging. 2015 Nov-Dec;25(6):989-95. doi: 10.1111/jon.12293. Epub 2015 Sep 22.

Abstract

Background and purpose: Two definitions of T1 hypointense (T1H) lesions can be derived from pre-contrast images: those that may or may not have a corresponding gadolinium-enhancing correlate on post-contrast images (T1H total), and those that are simultaneously non-gadolinium-enhancing on post-contrast scans (T1H non-enhancing). To determine the differences in lesion evolution between these two T1H definitions, we examined the effect of glatiramer acetate 40 mg/mL three times weekly subcutaneous injection (GA40) on the number of new or enlarging T1H total and T1H non-enhancing lesions in patients with relapsing-remitting multiple sclerosis (RRMS).

Methods: The Phase III GALA study randomized 1404 RRMS subjects 2:1 to receive GA40 or placebo for 12 months. MRI scans were obtained at baseline and at months 6 and 12. Cumulative numbers of T1H total and of T1H non-enhancing lesions were analyzed using an adjusted negative binomial regression model. A total of 1,357 patients had MRI data collected at either the month 6 or month 12 visit.

Results: Among the 1,357 patients with MRI scans performed at either the month 6 or month 12 visit, 883 treated with GA40 developed an adjusted cumulative mean of 1.72 T1H total lesions versus 2.62 in 440 placebo controls (risk ratio, .66; 95% CI, .54-.80; P < .0001). On T1H non-enhanced scans, GA40-treated patients developed an adjusted cumulative mean of 1.35 T1H non-enhancing lesions versus 1.91 in placebo controls (risk ratio, .71; CI, .58-.87; P = .0009).

Conclusions: GA40 significantly reduced the number of new or enlarging T1H total lesions and T1H non-enhancing lesions compared with placebo. Although the treatment effect magnitude was comparable with both definitions, the use of T1H non-enhancing lesions may be more relevant for more uniform standardization in future clinical trials.

Keywords: Glatiramer acetate; T1 hypointense lesions; gadolinium-enhancing lesions; relapsing-remitting multiple sclerosis.

Publication types

  • Clinical Trial, Phase III
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Brain / diagnostic imaging
  • Brain / drug effects*
  • Drug Administration Schedule
  • Female
  • Gadolinium
  • Glatiramer Acetate / administration & dosage
  • Glatiramer Acetate / pharmacology
  • Glatiramer Acetate / therapeutic use*
  • Humans
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / pharmacology
  • Immunosuppressive Agents / therapeutic use*
  • Magnetic Resonance Imaging*
  • Male
  • Middle Aged
  • Multiple Sclerosis, Relapsing-Remitting / diagnostic imaging
  • Multiple Sclerosis, Relapsing-Remitting / drug therapy*
  • Treatment Outcome

Substances

  • Immunosuppressive Agents
  • Glatiramer Acetate
  • Gadolinium