Tim Spelman1, Jonatan Freilich2, Bengt Anell3, Schiffon L Wong4, Jan Hillert5. 1. Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden. Electronic address: tim.spelman@ki.se. 2. Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden; Parexel International, Stockholm, Sweden. 3. Parexel International, Stockholm, Sweden. 4. EMD Serono Research and Development Institute, Inc, Billerica, MA, USA. 5. Department of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden.
Abstract
PURPOSE: This study aims to compare the disease progression and disease-modifying treatment-switching patterns between patients with high-disease-activity (HDA) relapsing-remitting multiple sclerosis (RRMS) and patients with low-disease-activity (LDA) RRMS in real-world clinical practice. METHODS: The confirmed disease progression and time to switch of 6647 patients from the Swedish multiple sclerosis registry were analyzed using a marginal structural model that compared patients with relapsing HDA (HDA-R) and lesion HDA (HDA-L) following definitions in European labels of disease-modifying therapies with patients with LDA. Time to milestone and stratified drug cohort analyses were used for internal validation. FINDINGS: A total of 262 patients with LDA, 985 patients with HDA-R, and 683 patients with HDA-L were included in the primary analysis. The HDA-R subgroup had statistically significant greater risk of disease progression (hazard ratio = 1.23; 95% CI, 1.03-1.46) and no difference in time to switch compared with the LDA subgroup. The HDA-L subgroup had statistically significant shorter time to switch (hazard ratio = 1.47; 95% CI, 1.31-1.66) and no difference in disease progression compared with the LDA subgroup. IMPLICATIONS: Compared with past research on HDA RRMS grounded mainly in randomized controlled trials of individual disease-modifying therapies, the main contribution of this study is that HDA, as identified by relapses, in real-world clinical settings has a clearer association with disease progression than HDA identified by new magnetic resonance imaging lesions. Taking into account that the HDA-L subgroup had a shorter time to switch, there is evidence of an unmet need for effective treatments in clinical practice for both the HDA-R and HDA-L subgroups.
PURPOSE: This study aims to compare the disease progression and disease-modifying treatment-switching patterns between patients with high-disease-activity (HDA) relapsing-remitting multiple sclerosis (RRMS) and patients with low-disease-activity (LDA) RRMS in real-world clinical practice. METHODS: The confirmed disease progression and time to switch of 6647 patients from the Swedish multiple sclerosis registry were analyzed using a marginal structural model that compared patients with relapsing HDA (HDA-R) and lesion HDA (HDA-L) following definitions in European labels of disease-modifying therapies with patients with LDA. Time to milestone and stratified drug cohort analyses were used for internal validation. FINDINGS: A total of 262 patients with LDA, 985 patients with HDA-R, and 683 patients with HDA-L were included in the primary analysis. The HDA-R subgroup had statistically significant greater risk of disease progression (hazard ratio = 1.23; 95% CI, 1.03-1.46) and no difference in time to switch compared with the LDA subgroup. The HDA-L subgroup had statistically significant shorter time to switch (hazard ratio = 1.47; 95% CI, 1.31-1.66) and no difference in disease progression compared with the LDA subgroup. IMPLICATIONS: Compared with past research on HDA RRMS grounded mainly in randomized controlled trials of individual disease-modifying therapies, the main contribution of this study is that HDA, as identified by relapses, in real-world clinical settings has a clearer association with disease progression than HDA identified by new magnetic resonance imaging lesions. Taking into account that the HDA-L subgroup had a shorter time to switch, there is evidence of an unmet need for effective treatments in clinical practice for both the HDA-R and HDA-L subgroups.
Authors: Mohammad Ehsanul Karim; Fabio Pellegrini; Robert W Platt; Gabrielle Simoneau; Julie Rouette; Carl de Moor Journal: Mult Scler Date: 2020-11-12 Impact factor: 5.855
Authors: David Ellenberger; Peter Flachenecker; Firas Fneish; Niklas Frahm; Kerstin Hellwig; Friedemann Paul; Alexander Stahmann; Clemens Warnke; Paulus S Rommer; Uwe K Zettl Journal: Brain Date: 2020-12-05 Impact factor: 13.501