Gilenya® data confirm reducing brain shrinkage matters for people with MS due to its association with long-term disability progression

Novartis announced today that new data presented at the Joint ACTRIMS-ECTRIMS Meeting in Boston, USA, reinforces the clinical importance of measuring brain shrinkage (brain volume loss) in multiple sclerosis (MS). An association between the rate of brain shrinkage and increased risk of long-term disability progression was confirmed in patients with MS¹. In pooled data from the phase III FREEDOMS core and extension studies, patients were categorized into four groups (quartiles) based on the mean change in brain volume from the start of the study to year-two. The analysis showed that 24.2% of patients who had the highest rate of brain shrinkage at 2 years had confirmed six-month disability progression at four years, compared to 15.4% of patients with the lowest rate of brain shrinkage (p=0.018)¹.

A separate analysis from the long-term follow-up extension study LONGTERMS, showed that the rate of brain shrinkage in patients treated with Gilenya^® (fingolimod) remained similar throughout the six-year period, between 0.33% and 0.46%². This was broadly in the range you would expect to see in people without MS, while the typical rate of brain shrinkage experienced by patients with MS is approximately 0.5% to 1.35% per year^3,4,5,6.

“Novartis is committed to generating data that advances science and clinical practice to improve the outcomes of patients. These new findings strengthen the link between brain shrinkage and long-term disability progression, supporting the significance of brain shrinkage for people with MS,” said Vasant Narasimhan, Global Head of Development at Novartis Pharmaceuticals. “The new data showing sustained low rates of brain shrinkage in Gilenya-treated patients with MS are reassuring because of the chronic debilitating nature of the disease.”

The rate of brain shrinkage for people with MS is around three to five times faster than people without the disease^3,4,5,6, and what is lost cannot be recovered. Brain shrinkage can start early,^7,8,9,10 often goes unnoticed and is associated with a loss of physical and cognitive (i.e. memory) function for patients with MS¹¹.

Analyses of the pooled data from the phase III FREEDOMS core and extension studies showed that irrespective of treatment received brain shrinkage was associated with future long-term disability progression².

References

1.  Jeffrey D et al. Brain volume change by quartile and disability progression in multiple sclerosis: a 4-year analysis of the phase 3 FREEDOMS trial and its extension. Abstract presented at: 2014 Joint ACTRIMS-ECTRIMS Meeting; September 10-13, 2014; Boston, Massachusetts. Abstract 36. Free communication FC2.3.
2. Radue E.W. et al. Sustained low rate of brain volume loss under long-term fingolimod treatment in relapsing multiple sclerosis: Results from the LONGTERMS study. Abstract presented at: 2014 Joint ACTRIMS-ECTRIMS Meeting; September 10-13, 2014; Boston, Massachusetts. Abstract 1346. Poster 439.
3. De Stefano N et al. Proportion of patients with BVL comparable to healthy adults in fingolimod phase 3 MS studies. Abstract presented at: 66th AAN Annual Meeting; April 26 – May 3, 2014; Philadelphia, Pennsylvania. Oral session S13:006.
4. Barkhof F et al. Imaging outcomes for neuroprotection and repair in multiple sclerosis trials. Nat Rev Neurol. 2009;5(5):256-266.
5. Bermel RA & Bakshi R. The measurement and clinical relevance of brain atrophy in multiple sclerosis. Lancet Neurol. 2006;5(2):158-170.
6. Hedman AM et al. Human Brain Changes Across the Life Span: a review of 56 longitudinal magnetic resonance imaging studies. Human Brain Mapping 2012; 33: 1987-220
7. Di Stefano N et al. Clinical Relevance of Brain Volume Measures in Multiple Sclerosis. CNS Drugs 2014; published online January 22, 2014.
8. Pérez-Miralles F et al. Clinical impact of early brain atrophy in clinically isolated syndromes. Mult Scler. Published online: May 7, 2013.
9. Filippi M et al. Evidence for widespread axonal damage at the earliest clinical stage of multiple sclerosis. Brain. 2003;126(Pt 2):433-437.
10. Filippi M et al. The contribution of MRI in assessing cognitive impairment in multiple sclerosis. Neurology 2010; 75: 2121-28.
11. Popescu V. et al; on behalf of the MAGNIMS Study Group. Brain atrophy and lesion load predict long term disability in multiple sclerosis. J Neurol Neurosurg Psychiatry. Mar 23, 2013.