Patterns and predictors of multiple sclerosis phenotype transition

• Published in: Brain communications Vol. 6; no. 6; p. fcae422
• Main Authors: Pontieri, Luigi, Greene, Nupur, Wandall-Holm, Malthe Faurschou, Geertsen, Svend Sparre, Asgari, Nasrin, Jensen, Henrik Boye, Illes, Zsolt, Schäfer, Jakob, Jensen, Rikke Marie, Sejbæk, Tobias, Weglewski, Arkadiusz, Mahler, Mie Reith, Poulsen, Mai Bang, Prakash, Sivagini, Stilund, Morten, Kant, Matthias, Rasmussen, Peter Vestergaard, Svendsen, Kristina Bacher, Sellebjerg, Finn, Magyari, Melinda
• Format: Journal Article
• Language: English
• Published: UK Oxford University Press 2024
• Subjects: real-world data; secondary progressive multiple sclerosis; registry study; multiple sclerosis
• ISSN: 2632-1297; 2632-1297
• DOI: 10.1093/braincomms/fcae422

Abstract Currently, there are limited therapeutic options for patients with non-active secondary progressive multiple sclerosis. Therefore, real-world studies have investigated differences between patients with relapsing-remitting multiple sclerosis, non-active secondary progressive multiple sclerosis and active secondary progressive multiple sclerosis. Here, we explore patterns and predictors of transitioning between these phenotypes. We performed a cohort study using data from The Danish Multiple Sclerosis Registry. We included patients with a relapsing-remitting phenotype, registered changes to secondary progressive multiple sclerosis and subsequent transitions between relapsing and non-relapsing secondary progressive multiple sclerosis, which was defined by the presence of relapses in the previous 2 years. We analysed predictors of transitioning from relapsing-remitting multiple sclerosis to relapsing and non-relapsing secondary progressive multiple sclerosis, as well as between the secondary progressive states using a multi-state Markov model. We included 4413 patients with relapsing-remitting multiple sclerosis. Within a median follow-up of 16.2 years, 962 were diagnosed with secondary progressive multiple sclerosis by their treating physician. Of these, we classified 729 as non-relapsing and 233 as relapsing secondary progressive multiple sclerosis. The risk of transitioning from relapsing-remitting to non-relapsing secondary progressive multiple sclerosis included older age (hazard ratio per increase of 1 year in age: 1.044, 95% confidence interval: 1.035–1.053), male sex (hazard ratio for female: 0.735, 95% confidence interval: 0.619–0.874), fewer relapses (hazard ratio per each additional relapse: 0.863, 95% confidence interval: 0.823–0.906), higher expanded disability status scale (hazard ratio per each additional point: 1.522, 95% confidence interval: 1.458–1.590) and longer time on disease-modifying therapies (hazard ratio per increase of 1 year in treatment, high-efficacy disease-modifying therapy: 1.095, 95% confidence interval: 1.051–1.141; hazard ratio, moderate-efficacy disease-modifying therapy: 1.073, 95% confidence interval: 1.051–1.095). We did not find significant predictors associated with the transition from relapsing secondary progressive multiple sclerosis to non-relapsing secondary progressive multiple sclerosis, whereas older age (hazard ratio per increase of 1 year in age: 0.956, 95% confidence interval: 0.942–0.971) prevented the transition from non-relapsing secondary progressive multiple sclerosis to relapsing secondary progressive multiple sclerosis. Our study suggests that transitioning from relapsing-remitting multiple sclerosis to non-relapsing secondary progressive multiple sclerosis depends on well-known factors affecting diagnosing secondary progressive multiple sclerosis. Further transitions between non-relapsing and relapsing secondary progressive multiple sclerosis are only affected by age. These findings add to the knowledge of non-active secondary progressive multiple sclerosis, a patient group with unmet needs in terms of therapies. Pontieri et al. found that 22% of patients diagnosed with relapsing-remitting multiple sclerosis had transitioned to secondary progressive multiple sclerosis after 22 years, and the majority were no longer experiencing relapses. These data support the view of multiple sclerosis being a continuum with varying contributions of relapsing and progressive biology. Graphical Abstract Graphical Abstract