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

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.