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

Abstract

BACKGROUND AND PURPOSETwo 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).METHODSThe 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.RESULTSAmong 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).CONCLUSIONSGA40 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.

An MRI-defined measure of cerebral lesion severity to assess therapeutic effects in multiple sclerosis

“…Consistent with this hypothesis, a placebo-controlled phase III clinical trial showed that the percentage of new cerebral lesions evolving into chronic T1 hypointensities was lower in GA-treated vs. placebo-treated RRMS patients [ 18 ]. Such a treatment effect of GA has been confirmed in subsequent studies of different patient populations [ 31 , 32 ]. In the present study, when comparing the change in zT1/T2 between groups, a significant difference was found favoring GA treatment vs. no treatment.…”

Higher satisfaction and adherence with glatiramer acetate 40 mg/mL TIW vs 20 mg/mL QD in RRMS

“…The rationale for this study design was the desire to assess the potential advantages of a less frequently administered (GA40) versus a more frequently administered formulation (GA20). The question of relatively efficacy between the GA40 and GA20 formulations has been evaluated in previous trials designed for that purpose (Khan et al, 2013;Zivadinov et al, 2018Zivadinov et al, , 2015.…”