Radue et al. Impact of Fingolimod Therapy on Magnetic Resonance Imaging Outcomes in Patients With Multiple SclerosisImpact of Fingolimod Therapy in Multiple Sclerosis.Arch Neurol. 2012 Jul 2:1-11. [Epub ahead of print]
OBJECTIVE To assess the impact of fingolimod (FTY720) therapy on magnetic resonance imaging measures of inflammatory activity and tissue damage in patients participating in a 2-year, placebo-controlled, phase 3 study.
DESIGN Patients with active relapsing-remitting multiple sclerosis were randomized to receive fingolimod, 0.5 mg; fingolimod, 1.25 mg; or placebo for 2 years. Standardized magnetic resonance imaging scans were obtained at months 0, 6, 12, and 24 and centrally evaluated for number and volume of T1 gadolinium-enhancing, T2 hyperintense, and T1 hypointense lesions and for percentage of brain volume change. Findings were compared across subgroups by treatment and baseline characteristics. SETTING Worldwide, multicenter clinical trial.
PATIENTS Patients were part of the fingolimod FTY720 Research Evaluating Effects of Daily Oral Therapy in Multiple Sclerosis (FREEDOMS) clinical trial for relapsing-remitting multiple sclerosis (N = 1272). MAIN OUTCOME MEASURES We measured the effect of therapy on acute inflammatory activity, burden of disease, and irreversible loss of brain volume.
RESULTS Fingolimod therapy resulted in rapid and sustained reductions in inflammatory lesion activity as assessed by gadolinium-enhancing and new/newly enlarged T2 lesions after 6, 12, and 24 months of therapy (P<0.001, all comparisons vs placebo). Changes in T2 hyperintense and T1 hypointense lesion volume also significantly favored fingolimod (P <0.05, all comparisons). Fingolimod, 0.5 mg (licensed dose), significantly reduced brain volume loss during months 0 to 6, 0 to 12, 12 to 24, and 0 to 24 (P<0.05, all comparisons) vs placebo, and subgroup analyses confirmed these effects over 2 years irrespective of the presence/absence of gadolinium-enhancing lesions, T2 lesion load, previous treatment status, or level of disability.
CONCLUSION These results, coupled with the significant reductions in relapse rates and disability progression reported previously, support the positive impact on long-term disease evolution.
TRIAL REGISTRATION NCT00289978.
We have already heard about the clinical effects of Gilenya in the FREEDOMS where it dropped the relapse rate by about 50-55%. This study reports the MRI imaging data. This again suggests that Gilenya is active in virtually all outcomes and a drop in clinical activity was associated with slowing of brain shrinkage.
CoI Multiple. This study was sponsored by Novartis the Maker of Gilenya
What is the relationship between brain atrophy and the progressive component of the disease? That is, most DMTs show an effect on brain atrophy but prove to be no help for those in the progressive phase of the disease. Yet progressive disease is all about ongoing loss of neurons, isn't it?
ReplyDeleteHow do you know this, when you say no help for progressive MS?
ReplyDeleteThe studies have not been completed in progressive MS yet, but are ongoing in PPMS.
Brain atrophy may be associated with cognitive decline, whereas EDSS is more associated with movement effects, which will involve notably the spinal cord and bits of the brain.
There is no doubt in my mind that stopping immunity from causing havoc in the brain is going to save nerves.
'There is no doubt in my mind that stopping immunity from causing havoc in the brain is going to save nerves.'
ReplyDeleteMD, do you mean that fingolimod could be beneficial for progressive MS?
There are clearly gadolium-enhancing progressive MSers, I am pretty confident that this group of MSers will respond positiviely to Gilenya.
ReplyDeleteNovaritis hope, as evidence shows, also that there are other targets besides the immune system that give Gilenya a chance that it will work in Progressive MS.
I have my views but what is important is that the trial is
ongoing and I belive fully recruited. we shall see. Hopefully it will work.