Patients With High-disease-activity Relapsing-Remitting Multiple Sclerosis in Real-world Clinical Practice: A Population-based Study in Sweden

Abstract

PurposeThis 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. MethodsThe 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. FindingsA 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. ImplicationsCompared 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.