Fingolimod (FTY720) reduces brain volume loss over 12 months compared with intramuscular interferon beta-1a: subgroup analyses of TRANSFORMS data based on inflammatory disease activity

BACKGROUND: Fingolimod (FTY720) 0.5mg once-daily is the first oral therapy approved in the European Union for relapsing–remitting multiple sclerosis (RRMS) with high disease activity. In the TRANSFORMS study, fingolimod 0.5mg not only significantly reduced brain volume loss by 32% over 1 year vs intramuscular (IM) interferon beta-1a (IFNB-1a), but had a favourable effect on MRI measures of inflammatory disease activity that could influence fluid shifts and volume changes. OBJECTIVES: To assess reductions in brain volume loss over 12 months in relation to MRI inflammatory disease activity at baseline or during therapy with fingolimod or IFNB-1a IM. METHODS: Here we studied patients with RRMS randomized to fingolimod 0.5mg or weekly IFNB-1a IM 30mcg for 12 months. Mean percentage brain volume change (PBVC) during months 0–12 was obtained using Structural Image Evaluation, using Normalisation, of Atrophy (SIENA); part of FSL. PBVC was analyzed in subgroups of patients with (n=245) or without (n=466) gadolinium-enhancing (Gd+) lesions at baseline, with (n=364) or without (n=350) new disease activity (Gd+ lesions and new/newly enlarged T2 lesions) at month 12, and with (n=440) or without (n=267) baseline Gd+ lesions and new disease activity at month 12. Between-group comparisons of PBVC were assessed using rank analysis of covariance adjusted by treatment, country, and baseline normalized brain volume. RESULTS: Over 12 months, fingolimod 0.5mg reduced PBVC more than IFNB-1a IM in all subgroups. In both treatment groups, PBVC was numerically greater in patients with baseline Gd+ lesions (fingolimod 0.5mg, –0.48%; IFNB-1a IM, –0.66%; p=0.178) than in those without Gd+ lesions (fingolimod 0.5mg, –0.22%; IFNB-1a IM, –0.32%; p=0.049), greater in patients with new disease activity at month 12 (fingolimod 0.5mg, –0.40%, IFNB-1a IM, –0.52%; p=0.023) than in those without such activity (fingolimod 0.5mg, –0.22%, IFNB-1a IM, –0.37%; p=0.046), and greater in patients with both baseline Gd+ lesions and new disease activity at month 12 (fingolimod 0.5mg, –0.39%, IFNB-1a IM, –0.55%; p=0.012) than in those without such activity (fingolimod 0.5mg, –0.19%, IFNB-1a IM, –0.26%; p=0.536). CONCLUSIONS: PBVC was greater in patients with inflammatory lesions than in those without. The effect of fingolimod vs IFNB-1a IM in reducing brain volume loss occurred irrespective of inflammatory lesion activity at baseline or new disease activity during 1 year of therapy.