Novartis Real World Data som presenterats på AAN bekräftar Gilenyas (fingolimod) effekt på behandling av MS

Novartis real-world data at AAN confirms benefit of Gilenya® on four key measures of disease activity in relapsing MS
*  Over 16 months, more than 75% of patients on Gilenya had either no relapses, no new or enlarged MRI lesions or no disability progression; around 58% showed brain shrinkage levels broadly within the range expected for people without MS
*  Approximately 60% of patients achieved NEDA-3 (no relapses, no MRI lesions and no disability progression combined) and 38% achieved NEDA-4 (NEDA-3 plus no brain shrinkage), further supporting findings from clinical trials
*  First real-world multicenter study showing that monitoring brain shrinkage using routine imaging methods is reliable and could be adopted in daily clinical practice

Novartis today announced data from the Phase IV Multiple Sclerosis and clinical outcome and MRI in the US (MS-MRIUS) study, which confirmed the effectiveness of Gilenya® (fingolimod) in the real-world setting, supporting previous findings from Phase III trials[1],[2]. Results show that Gilenya impacted four key measures of MS disease activity (relapses, MRI lesions, disability progression and brain shrinkage), in people with relapsing-remitting multiple sclerosis (RRMS) for up to 16 months[1]. This is also the first time a multicenter study has evaluated and shown that routine magnetic resonance imaging (MRI) scans taken in the every-day clinical setting can reliably be used to measure brain shrinkage, a key measure of disease progression, in people with RRMS[3]. Full results are presented at the 69th American Academy of Neurology (AAN) Annual Meeting, in Boston, Massachusetts, USA.

The MS-MRIUS study is a multicenter (33 centers), retrospective, real-world study of 590 people with RRMS receiving Gilenya treatment[1]. At median follow-up of 16 months, 85.8% of individuals treated with Gilenya remained on treatment[1]. Of individuals eligible for NEDA-3 assessment (no relapses, no new or enlarged MRI lesions and no disability progression combined, n=586), 59.6% achieved NEDA-3 status[1]. Of those eligible for NEDA-4 assessment (NEDA-3 plus no brain shrinkage (brain volume loss), n= 325), more than a third (37.5%) achieved NEDA-4 status[1]. The study showed that among the NEDA-4 patients, 86.5% treated with Gilenya had no relapses, 91.1% experienced no disability progression and 79.7% had no new or enlarged MRI lesions[1]. In addition, 58.2% of patients had no MS-related brain shrinkage over 0.4%, which is broadly within the range one would expect to see in people without MS[1].

”These data build on the wealth of clinical and real-world evidence that show Gilenya is a highly efficacious, long-term treatment option for controlling disease activity in relapsing MS,” said Vas Narasimhan, Global Head of Drug Development and Chief Medical Officer, Novartis. ”Measuring brain shrinkage has historically been dependent on specialist brain scanning techniques. These ground-breaking new data showing brain shrinkage can be reliably measured by routine MRI scans have the potential to change how this key measure of disease progression is monitored, to ultimately help patients and physicians observe and manage treatment success and outcomes.”

The data showed for the first time that MRI scans with techniques readily available in clinical practice (FLAIR – fluid attenuation inversion recovery MRI), was a reliable method for measuring brain shrinkage in more than 95% of people included in the study[3].

Results from the MS-MRIUS study confirm the importance of addressing the four key measures of MS disease activity – relapses, MRI lesions, disability progression and brain shrinkage – through early and effective treatment to impact the course of RRMS and preserve patients’ physical and cognitive function over the long-term.

About the MS-MRIUS study
The Multiple Sclerosis and clinical outcome and MRI in the US (MS-MRIUS) study is a Phase IV multicenter (33 sites), retrospective study including 590 people with relapsing-remitting multiple sclerosis (RRMS)[1]. The study investigated the effect of Gilenya on achieving ’no evidence of disease activity’ (NEDA), magnetic resonance imaging (MRI) efficacy measures among people with RRMS, and also the feasibility of measuring brain shrinkage in routine clinical practice[1]-[3]. 586 patients were eligible for NEDA-3 and 325 patients were eligible for NEDA-4 evaluation, based on the availability of high resolution scans[1].

Individuals were required to undergo MRI scans within six months before, or one month after, the start of Gilenya treatment, followed by another MRI scan between nine and 24 months after the start of treatment[1].

Evaluation of NEDA was based on measurement of annualized relapse rate, MRI lesions and disability progression, as measured by the mean Expanded Disability Status Scale (EDSS) score, (NEDA-3) and MS-related brain shrinkage (NEDA-4), measured using whole brain volume loss (no MS-related brain shrinkage >0.4%)[1].

To assess the feasibility of measuring brain shrinkage in routine clinical practice, changes in lateral ventricle volume (LVV) were evaluated using fluid attenuation inversion recovery (FLAIR) MRI scans. LVV could be used as a proxy for whole brain volume changes, measured in high resolution MRI scans[3].

References
[1] Weinstock-Guttman B et al. Assessing no evidence of disease activity status in patients with relapsing-remitting multiple sclerosis receiving fingolimod: results from a longitudinal, multicenter, real-world study. Poster presented at the 69th American Academy of Neurology Annual Meeting; April 22-28, Boston, Massachusetts, USA. Poster 388.
[2] Zivadinov R et al. Impact of fingolimod on MRI brain volume measures in routine clinical practice: results from MS-MRIUS, a longitudinal observational, multicenter real-world outcome study in RRMS patients. Poster presented at the 69th American Academy of Neurology Annual Meeting; April 22-28, Boston, Massachusetts, USA. Poster 350.
[3] Dwyer MG et al. Feasibility of brain atrophy measurement in clinical routine: Results from MS-MRIUS, a longitudinal observational, multicenter real-world outcome study in RRMS patients. Platform presentation at the 69th American Academy of Neurology Annual Meeting; April 22-28, Boston, Massachusetts, USA. Abstract 004.
[4] Gilenya US Prescribing Information. https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/gilenya.pdf (link is external). Accessed April 2017.
[5] Brinkmann V et al. FTY720 (fingolimod) in Multiple Sclerosis: therapeutic effects in the immune and the central nervous system. Br J Pharmacol. 2009;158(5):1173-1182.
[6] De Stefano N et al. Effect of fingolimod on diffuse brain tissue damage in relapsing-remitting multiple sclerosis patients. Mult Scler Relat Disord. 2016;7:98-101.
[7] Warrender-Sparkes M et al. The effect of oral immunomodulatory therapy on treatment uptake and persistence in multiple sclerosis. Mut Scler. 2016;22(4):520-532.
[8] Khatri B et al. Comparison of fingolimod with interferon beta-1a in relapsing-remitting multiple sclerosis: a randomised extension of the TRANSFORMS study. Lancet Neurol. 2011;10(6):520-529.
[9] Giovannoni G et al. ”No evident disease activity”: The use of combined assessments in the management of patients with multiple sclerosis. Mult Scler. 2017. Doi 10.1177/1352458517703193.
[10] De Stefano N et al. Effect of Fingolimod on Brain Volume Loss in Patients with Multiple Sclerosis. CNS Drugs. 2017;31(4):289-305.
[11] Kappos L et al. Inclusion of brain volume loss in a revised measure of ’no evidence of disease activity’ (NEDA-4) in relapsing-remitting multiple sclerosis. Mult Scler. 2016;22(10):1297-1305.
[12] Lizac N et al. Highly active immunomodulatory therapy ameliorates accumulation of disability in moderately advanced and advanced multiple sclerosis. J Neurol Neurosurg Psychiatry. 2017;88(3):196-203.
[13] Gilenya EMA Summary of Product Characteristics. http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/002202/WC500104528.pdf (link is external). Accessed April 2017.
[14] Data on file. Novartis Pharmaceuticals.
[15] PubMed Heath. Multiple Sclerosis (MS). http://www.ncbi.nlm.nih.gov/pubmedhealth/PMH0001747/ (link is external) (link is external). Accessed April 2017.
[16] MS Society. Types of MS. https://www.mssociety.org.uk/what-is-ms/types-of-ms (link is external). Accessed April 2017.
[17] Multiple sclerosis international federation. Atlas of MS 2013. https://www.msif.org/wp-content/uploads/2014/09/Atlas-of-MS.pdf (link is external). Accessed April 2017.