T. Hach
Novartis Pharma AGAuthor Of 2 Presentations
P0238 - Sustained reduction of disability and cognitive decline with long-term siponimod treatment in patients with active SPMS: EXPAND data up to 5 years (ID 1471)
Abstract
Background
In the EXPAND Core part, in the subgroup of patients with active secondary progressive multiple sclerosis (aSPMS: presence of relapses in the 2 years prior to screening and/or ≥1 T1 gadolinium-enhancing (Gd+) lesion at baseline), siponimod reduced the risk of 3-/6-month confirmed disability progression on Expanded Disability Status Scale (3m/6mCDP) by 31% and 37%, respectively, and the risk of decline in cognitive processing speed (CPS, 6-month confirmed cognition worsening of ≥4-point on Symbol Digit Modalities Test [6mCCW]) by 27% versus placebo.
Objectives
To assess the long-term efficacy and safety of siponimod in patients with aSPMS in the Core and Extension parts of the EXPAND study.
Methods
In patients with aSPMS who had received ≥1 dose of randomized treatment during Core part, and who entered the Extension (36 month extension data cut-off [6 April 2019]; total study duration ≤5 years), time to 3m/6mCDP, 6mCCW, and annualized relapse rate (ARR) were assessed for the Continuous (siponimod in the Core and Extension) and Switch (placebo in the Core and switched to open-label siponimod in the Core/Extension) groups.
Results
Of the 1651 patients randomized in the EXPAND Core part, 779 were with aSPMS (Continuous group: N=516; Switch group: N=263), of which 582 entered the Extension. The risk of 6mCDP was reduced by 29% (0.71 [0.57‒0.90]; p=0.0044) for the Continuous versus Switch group, corresponding to an about 70% delay in time to 6mCDP across the 25th–40th percentile). Median time to 6mCDP was 48 months for the Switch group and was not reached for the Continuous group. The risk of 6mCCW for the Continuous versus Switch group was reduced by 33% (0.67 [0.53‒0.86]); p=0.0018), corresponding to an about 70% delay in time to 6mCCW across the 25th–30th percentile, median time to 6mCCW (55.5 months) was reached only for the Switch group. In patients without active disease, a nonsignificant trend for reduced risk of disability progression and cognitive worsening was observed for the Continuous vs Switch groups. A significant reduction in ARR for the Continuous versus Switch groups was observed in patients with (0.08 vs 0.12; p=0.0023) or without active disease (0.03 vs 0.08; p<0.0001).
Conclusions
In EXPAND, long-term data analyses in the Continuous versus Switch groups showed that siponimod treatment effects on disability, cognitive processing speed, and relapse outcomes in patients with active SPMS are sustained for up to 5 years, and highlight the value of early treatment initiation.
P0482 - Objective classification methods result in an increased proportion of secondary progressive multiple sclerosis in five patient registries (ID 1120)
Abstract
Background
Secondary progressive MS (SPMS) is a research area that is attracting more attention as better treatment options are still needed for this patient group. The assignment of SPMS by clinicians can differ between countries and may be influenced by drug prescription guidelines, reimbursement issues and other societal limitations.
Objectives
To compare the clinically assigned SPMS proportion to three objective SPMS classification methods in five MS registries.
Methods
Data from MS registries in the Czech Republic (CR) (11,336 patients), Denmark (10,255 patients), Germany (23,185 patients), Sweden (11,247 patients) and the United Kingdom (UK) (5,086 patients) were used. Inclusion criteria were patients with relapsing remitting (RR)MS or SPMS with age ≥ 18 years at the beginning of the index period (1 January 2017 – 31 December 2019). In addition to clinically assigned SPMS three different classification methods were applied; method 1: modified real world EXPAND criteria (Kappos et al, Lancet 2018:391; 1263-1273), method 2: the data-derived definition from Melbourne University without the pyramidal Functional Systems Score (Lorscheider et al, Brain 2016:139; 2395-2405) and method 3: the decision tree classifier from Karolinska Institutet (Ramanujam, R. et al., 2020. medRxiv, 2020.07.09.20149674).
Results
The SPMS proportions per registry, when comparing the clinically assigned SPMS with the results of the three classification methods, were CR: 8.8%, 21.3%, 22.1%, 25.0%; Denmark: 15.5%, 27.5%, 25.4%, 28.0%; Germany: 15.6%, 15.4%, 16.7%, 25.4%; Sweden: 23.7%, 20.8%, 23.2%, 24.6% and UK: 34.3%, 21.7%, 38.4%, 58.3% for clinical SPMS and methods 1, 2 and 3, respectively.
Conclusions
The proportion of clinically assigned SPMS patients varies between MS registries. When applying other classification methods, the SPMS proportion generally increases but remains variable between registries. As some of the classification methods have extensive requirements regarding data density, the number of unclassifiable samples created are considerable for some of the registries, which will influence the results. Providing a classification method that depends on objective information could prove useful when attempting to estimate the proportion of SPMS patients in MS populations but the choice of method may depend on the data characteristics of the individual MS registry.