Epidemiologic and Clinical Highlights in MS Care From ECTRIMS 2021

Ruth Ann Marrie, MD, PhD, FRCPC, FCAHS

Over the course of the 37th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), October 13-15, a vast number of data sets were presented, highlighting the research that is being conducted into the epidemiology, clinical care, and intervention of multiple sclerosis (MS).

In the final day’s plenary session, which included the Charcot Lecture, various clinical highlights were presented, including some underlined works identified by Ruth Ann Marrie, MD, PhD, FRCPC, FCAHS, professor of medicine and community health sciences, Max Rady College of Medicine, University of Manitoba. These included works focused on the epidemiology of MS, as well as some data offering practical insights for clinical care.¹

Genetic Implications of MS

She began with work from Marijne Vandebergh, PhD, fellow, Laboratory for Neuroimmunology, KU Leuven, and colleagues which identified an HR of 2.03 (95% CI, 1.55-2.67) in the discovery cohort (n = 506), 2.53 (95% CI, 1.58-4.05) in the replication cohort (n = 485), and 2.15 (95% CI, 1.70-2.78) in the cohorts combined (n = 991). The discovery cohort had a baseline age of 31 years and duration of disease of 4 years (range, 1.35-12.07) while the replication cohort had a baseline age of 33 years and duration of disease of 0.50 years (range, 0.25-2.57).²

“As you know, multiple sclerosis is a highly heterogeneous condition, and as relapses are the hallmark of disease, Vandebergh et al looked at genetic factors that might account for differences in relapse rate,” Marrie said in the plenary.¹ “They found that WNT9B was associated with more than double the hazard for a relapse. Interestingly, this particular factor is associated with nervous system development, providing potential areas for future investigation in terms of contributing genetic factors.”

READ MORE: Stable Immunity Observed After COVID-19 Infection in Patients With Multiple Sclerosis

Comorbidity and MS Disease Progression

Marrie then highlighted work from Stefanie Binzer, MD, PhD, Department of Neurology, Sygehus Lillebaelt, and colleagues, in which the group focused on the role of comorbidity in MS disease progression, utilizing data from the Swedish MS Registry. In a cohort of 8972 patients, they identified that 1.0% (n = 88) had type 1 diabetes, 0.9% (n = 78) had ulcerative colitis, and 0.9% (n = 77) had Crohn disease.³

Ultimately, they observed that type 1 diabetes and Crohn disease, along with comorbidity overall—as measured by the Charlson’s Summary Comorbidity Index—were associated with faster time to Expanded Disability Status Scale (EDSS) scores of 3, 4, and 6. “This highlights the critical importance of preventing comorbidity, as well as early intervention and treatment as mechanism to reduce adverse outcomes,” Marrie said.

Disease Progression Independent of Relapse Activity

“As we continue to try and understand factors that contribute to the accumulation of disability progression, the Italian group led by [Mattia] Fonderico, [MD, research assistant, University of Florence] looked at factors associated with relapse-associated worsening vs progression independent of relapse activity, or PIRA,” Marrie said. She noted that a particularly interesting finding from the work was that observed percentage of time spent on disease-modifying therapy (DMT) for MS was associated with PRIA.⁴

Fonderico et al observed that those individuals who had spent more time on DMT had a lower risk of PIRA (HR, 0.18 [95% CI, 0.15-0.21]) compared with those with less time (P <.001). Disease duration had the highest HR, at 1.52 (95% CI, 1.25-1.85; P <.001), followed by disease course, defined as either relapsing–remitting or clinically isolated syndrome, at 1.44 (95% CI, 1.28-1.61; P <.001). The total patient sample included 5287 individuals with a mean baseline age of 31.8 years (±9.9), mean disease duration of 0.42 years (±0.27), and a mean EDSS of 1.7 (±1.2).⁴

Treatment Initiation Options

Among the final highlights summarized by Marrie was the work of Peter Alping, MD, clinical assistant and PhD student, Department of Clinical Neuroscience, Karolinska Institutet, and colleagues in the COMBAT-MS trial, which assessed the effectiveness of initial MS treatment options. The options assessed included injectables (n = 585), dimethyl fumarate (Tecfidera; Biogen)(n = 339), natalizumab (Tysabri; Biogen)(n = 269), and rituximab (Rituxan; Genentech) (n = 472), all used as first-ever therapies for 1938 instances of treatment initiation.

All told, they observed that the lowest risk of relapse, of MRI lesions, and the lowest probability of switching were all associated with rituximab use, with similar EDSS scores at 3 years to the other agents, though slightly worse with injectables. Compared with rituximab, the HRs for relapse were 6.0 (95% CI, 3.7-9.6) for injectables, 2.9 (95% CI, 1.7-4.8) for dimethyl fumarate, and 1.8 (95% CI, 1.0-3.3) for natalizumab.⁵

“[These data point] to a possible value of using more effective therapies at the beginning of the disease,” Marrie said. “Nonetheless, given that the EDSS still worsened, we’re still in need of additional therapies.”

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REFERENCES
1. Marrie RA. Clinical Highlights. Presented at ECTRIMS Congress 2021; October 13-15; Virtual. Session 61815.
2. Vandebergh M, Andlauer T, Zhou Y, et al. Genetic variation in WNT9B increases relapse hazard in multiple sclerosis. Presented at ECTRIMS Congress 2021; October 13-15; Virtual. Presentation 078
3. Binzer S. Concomitant autoimmunity and risk of multiple sclerosis worsening. Presented at ECTRIMS Congress 2021; October 13-15; Virtual. Presentation P129
4. Fonderico M, Portaccio E, Bellinvia A, et al. Progression independent of relapse activity in early multiple sclerosis patients. Presented at ECTRIMS Congress 2021; October 13-15; Virtual. Presentation 037
5. Alping P, Burman J, Fink K, et al. Effectiveness of initial MS treatments in the COMBAT-MS trial: injectables, dimethyl fumarate, natalizumab, and rituximab. Presented at ECTRIMS Congress 2021; October 13-15; Virtual. Presentation 078