Author Of 1 Presentation
PS05.02 - Validation of three Secondary Progressive Multiple Sclerosis classification methods in five registries within the SPMS Research Collaboration Network
Abstract
Background
Assigning Secondary Progressive Multiple Sclerosis (SPMS) course consistently is challenging as it is based on a gradual worsening in neurological disability independent of relapses. Clinical SPMS assignment may therefore vary between registries depending on clinical practice. Consequently, a comparison of SPMS between registries would benefit from an objective definition of SPMS.
Objectives
To validate three different methods for classifying patients into Relapsing Remitting Multiple Sclerosis (RRMS) or SPMS, compared to the clinical assignment, in five European Multiple Sclerosis (MS) registries.
Methods
Data from MS registries in Czech Republic (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. Patients with either RRMS or SPMS, age ≥ 18 years at index date (date with the latest Expanded Disability Status Scale (EDSS) observation) were included. Index period was 01/2017 - 12/2019. Three EDSS centric classification methods were applied; method 1: a modified real world EXPAND criteria (Kappos, L. et al., 2018. The Lancet 391(10127), 2018), method 2: the data-derived definition from Melbourne University but without pyramidal Functional Score (Lorscheider, J. et al., 2016. Brain 139(9)), method 3: the decision tree classifier from Karolinska Institutet (Ramanujam, R. et al., 2020. medRxiv, 2020.07.09.20149674). The classifications were compared to the clinical assignment, where sensitivity (SPMS as true positive), specificity (RRMS as true negative) and accuracy were calculated as similarity measurements.
Results
The overall classification performance (sensitivity, specificity, accuracy) among classifiable patients were; method 1: (0.47, 0.85, 0.79), method 2: (0.77, 0.87, 0.85), method 3: (0.84, 0.83, 0.84). The proportions of unclassifiable patients with each method were; method 1: 20.0%, method 2: 32.2%, method 3: 0%. Methods 2 & 3 provided a high sensitivity, specificity and accuracy, while method 1 provided high specificity but low sensitivity. Method 3 was the only method having no unclassifiable patients.
Conclusions
Our findings suggest that these methods can be used to objectively assign SPMS with a fairly high performance in different registries. The method of choice depends on the research question and to what degree unclassifiable patients are tolerable.
Author Of 3 Presentations
P0145 - Relation of EDSS to patient-reported outcome measurements in MS: Real-world data from a Swedish nationwide study of fingolimod (IMSE 2) (ID 674)
Abstract
Background
Fingolimod (FGL) is an oral disease-modifying therapy (DMT) for patients with relapsing-remitting multiple sclerosis, introduced in Sweden 2011. Already from launch, FGL was included in the Swedish “Immunomodulation and Multiple Sclerosis Epidemiology Study” (IMSE) in order to enable long-term surveillance of effectiveness and safety aspects in a large population-based cohort.
Objectives
To assess the relation between Expanded Disability Status Scale (EDSS) and patient-reported outcome measurements (PROMS) in patients treated with FGL.
Methods
Swedish MS patients are registered into the nationwide Swedish MS Registry. Demographic data, EDSS and the Multiple Sclerosis Impact Scale (MSIS-29), Symbol Digit Modalities Test (SDMT), European Quality of Life - 5 Dimensions Test (EQ-5D), Visual Analog Scale (VAS) were collected for FGL patients who agreed to participate in the IMSE 2 study. Spearman rank correlation were used to determine associations between EDSS and PROMS.
Results
From September 2011 until June 2020, 1670 MS patients (68% female) were included in IMSE 2. Mean age at treatment start was 39 years and mean treatment duration in the entire cohort was 44 months (M). Out of 1670 patients, 560 (63% female) had been treated with FGL for at least 60 M. Mean age was 40 years and mean treatment duration 81 M. Significant (p<0.05) correlations was found between EDSS and all PROMs. The strongest correlation was found between the physical component of MSIS-29 for both baseline (r=0.60, n=778) and 60 M (r=0.64, n=109). Also, for both EQ-5D and VAS, Spearman coefficient indicates a moderate correlation for baseline (EQ-5D; r=-0.48, n=744 and VAS; -0.43, n=706) and 60 M (EQ-5D; r=-0.47, n=102 and VAS; -0.48, n=102) respectively. The correlation between EDSS and SDMT and the psychological component of MSIS-29, both indicated a weak correlation for baseline (SDMT; r=-0.28, n=771 and MSIS-29 psychological; r=0.28, n=778). For 60 M the correlations were stronger and indicated a moderate correlation (SDMT; r= -0.42, n=114 and MSIS-29 psychological; r=0.33, n=109).
Conclusions
The observed correlations between EDSS and PROMs in patients treated with FGL indicate a weak correlation with SDMT and the psychological component of MSIS-29. These results highlight that different scales capture different dimensions of the physical and psychological impact of MS from the patient’s perspective and have important functions which should continue to be followed.
P0420 - Performance on Symbol Digits Modalities Test preceding conversion to Secondary Progressive Multiple Sclerosis (ID 1254)
Abstract
Background
In an era of emerging new therapies for SPMS, neurologist are searching for robust tools to predict and identify conversion to SPMS. Cognitive impairment is prevalent in 40-75% of MS patients and supposedly more common in SPMS as it increases with age. Symbol Digits Modalities Test (SDMT) is a sensitive, easy administrated test of information processing speed and predicts driving capacity and future income in MS populations.
Objectives
In this pilot study we test if SDMT absolute values could be used to predict SPMS conversion, hypothesizing that SPMS patients prior to conversion have lower scores on SDMT compared to age and gender matched RRMS patients.
Methods
This is a Swedish MS Registry-based study. We extracted first SDMT score and age at testing, available for MS patients included in the registry. Then we selected RRMS patients with first SDMT value at least 4 years (mean ± SD, 6.5 ± 1.98) before SPMS onset n=192 (SPMS converters) and gender matched RRMS patients (n=192) that performed their first SDMT at the same age as SPMS converters. We performed a linear regression analysis using SDMT as dependent variable and age, gender, disease course (SP convert) as independent variables.
Results
RRMS patients that later converted to SPMS, had statistically significant lower SDMT values compared to age and gender matched RRMS patients, p=3.43x10-13. Overall, SDMT decreased with age and was lower for men compared to women (p=0.0002 and p=0.024).
Conclusions
Differences in SDMT absolute values correlate with and precede SPMS conversion at the group level. High variation of inter-individual SDMT performance is likely to limit the usefulness of SDMT to predict SPMS by itself, but SDMT could be an integrated component of a more complex prediction algorithm.
P0834 - A comparative study of teriflunomide and dimethyl fumarate within the Swedish MS Registry (ID 838)
Abstract
Background
Background: Teriflunomide and dimethyl fumarate first-line have similar labels and are used in similar patients and hence provide a suitable comparison.
Objectives
The objective of this study was to compare the effectiveness of teriflunomide and dimethyl fumarate (DMF) in a Swedish real-world setting.
Methods
All relapsing remitting multiple sclerosis (RRMS) patients in the Swedish MS registry initiating teriflunomide or DMF were included in the analysis. The primary endpoint was treatment persistence. Secondary outcomes included annualised relapse rate (ARR); time to first on-treatment relapse, confirmed disability progression and improvement, and patient reported outcomes. Propensity score matching was used to adjust comparisons for baseline confounders. Marginal Cox models were used to compare time-to-event outcomes by matched treatment groups.
Results
Of the 358 teriflunomide and 1767 DMF patients eligible for the analysis, 353 teriflunomide patients were successfully matched to 353 DMF on a 1:1 basis. There was no difference in the rate of overall treatment discontinuation by treatment group across the entire observation period (HR 1.12; 95% CI 0.91, 1.39; p=0.277; reference=teriflunomide). Within the subset of the patients who discontinued their index treatment, the most frequently reported reason for DMF discontinuation was side effects (89/190; 46.8%) whilst lack of effectiveness was reported in 39/190 (20.5%) of discontinuations. By comparison, lack of effectiveness was cited as the most frequent discontinuation reason in the matched teriflunomide group (72/160; 45%) followed by side effects (63/160; 39.4%). ARR was comparable (p=0.237) between DMF (0.07; 95% CI 0.05-0.10) and teriflunomide (0.09; 95% CI 0.07-0.12). Similarly, there was no difference in time to first on-treatment relapse (HR 0.78; 95% CI 0.50, 1.21; p=0.270; reference=teriflunomide). Furthermore, there was no difference by matched treatment group in the rate of six-month confirmed disability progression (HR 0.55; 95% CI 0.27, 1.12; p=0.100; reference=teriflunomide) or six-month confirmed disability improvement (HR 1.17; 95% CI 0.57, 2.36; p=0.672; reference=teriflunomide). MSIS-29 quality of life scores were also similar over time between the two groups.
Conclusions
This population-based real-world study performed on the Swedish MS registry shows similarities in treatment persistence, clinical effectiveness and quality of life outcomes of teriflunomide and dimethyl fumarate.