Recapping Research From 2023 CMSC Annual Meeting

In recent months, the NeurologyLive® team has been covering the news and conducting interviews with experts on the latest updates in the clinical care of patients with neurological diseases, such as dementia or Alzheimer, epilepsy, headache or migraine, movement disorders, multiple sclerosis (MS), neuromuscular diseases, sleep medicine, and stroke.

To recap the 2023 Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting, held May 31 to June 3, in Aurora, Colorado, the team has culminated some of the biggest pieces of news to offer updates on new developments in the literature about MS to spread awareness on prevention and treatment approaches.

Click here for more coverage of CMSC 2023.

Latest Literature

Low-Fat Diet Intervention Demonstrates Significant Impact on Multiple Sclerosis Fatigue

Findings from a randomized, controlled study of individuals with relapsing MS showed significant effects on fatigue while on a low-fat diet over a 12-week period.¹ The study included 39 individuals who were randomly assigned to either low-fat diet (n = 20) or wait-list diet (n = 19), or control, for 14 weeks. The diet group received 1 to 2 weeks of nutrition counseling followed by a strict adherence to a low-fat diet for 12 weeks, with diet adherence measured by a monthly food frequency questionnaire and 24-hour food recall. The study used change in Modified Fatigue Impact Scale (MFIS) as the primary end point, with several other secondary and clinical outcomes.

Between the 2 groups, the diet group had a higher mean age (52 [±10] years vs 47 [±13]) and a higher mean Expanded Disability Status Scale (EDSS) score (4.2 [±1.3] vs 3.4 [±1.4]). At the end of the randomized, 14-week period, findings showed a mean decrease in MFIS of 4.00 (95% CI, –12.04 to 4.04) in comparison with controls. Fatigue Severity Scale (FSS), another major outcome, was decreased by 0.41 (95% CI, –1.18 to 0.36) in those on the low-fat diet in relation to controls.

After excluding 5 specific outliers, sensitivity analyses further strengthened the magnitude of association with a mean MFIS decrease of 13.93 (95% CI, –20.65 to –7.20) and mean FSS decrease of 1.22 (95% CI, –1.94 to –0.50) in comparison with controls. Patients on the low-fat diet also saw additional benefits, with a decrease of 10.56% (95% CI, –18.50% to –2.97%) in calories from fat compared with controls.

Ublituximab Outperforms Teriflunomide in Improving Fatigue in Multiple Sclerosis

Post hoc data from the phase 3 ULTIMATE studies (NCT03277261; NCT03277248) showed that treatment with ublituximab (Briumvi; TG Therapeutics), a recently approved therapy for relapsing forms of MS, resulted in greater improvements in fatigue in comparison with teriflunomide (Aubagio; Sanofi).² Using the Fatigue Impact Scale (FIS), investigators observed significantly greater reductions with ublituximab across all individual time points (week 24: –6.4 vs –3.1; P = .027; week 48: 8.2 vs –4.4; P = .018; week 96: –9.1 vs –4.4; P = .008).

Ublituximab, an agent designed to target a unique epitope on CD20-expressing B-cells, was approved based on the ULTIMATE trials, which featured 1094 patients with relapsing MS across 10 countries. In the studies, patients received either 1-hour infusion of ublituximab 450-mg intravenously every 24 weeks or teriflunomide 14 mg orally once daily for 96 weeks. The analysis included subgroups of individuals with baseline FIS score less than or equal to median or greater than median.

Across the individual time points, ublituximab outperformed teriflunomide on FIS physical dimension score (week 24: –2.4 vs –1.4; P = .029; week 48: –2.9 vs –1.6; P = .009; week 96: –3.2 vs –1.4; P = .001). The anti-CD20 therapy also showed significantly greater reductions in cognitive dimension score at weeks 24 and 48 and in social dimension score at week 96 (P <.05). Among those with baseline FIS score less than or equal to median, FIS total score was significantly improved from baseline in favor of ublituximab at week 48 (–1.3 vs 3.0; P = .007) and week 96 (–1.5 vs 4.8; P = .001). In contrast, in the subgroup with baseline FIS score greater than median, no significant differences were observed for ublituximab vs teriflunomide at any time point.

Mindfulness-Based Stress Reduction Intervention Shows Potential to Treat Silent Symptoms of Multiple Sclerosis

In a recently concluded small-scale study of individuals with MS, implementation of a mindfulness-based stress reduction (MBSR) intervention resulted in several positive benefits on patient-reported outcomes (PROs).³ The study featured 23 females with relapsing-remitting MS who were offered 8 weeks of MBSR free of charge. After a 12-week observation period, treatment with MBSR was associated with robust (d >.08) improvements across a range of unadjusted PROs, including stress, anxiety, depression, fatigue, loneliness, well-being, and interoceptive awareness (all P <.01).

The cohort of individuals assessed had a median Expanded Disability Status Scale score of 2.0 (±1.2) and showed no new clinical/MRI disease activity during the 12-week observation period. More than half (57%) were on a B-cell depleting agent, and 91% completed the course.

The conserved transcriptional response to adversity (CTRA) score was determined using well-established methods from 53 prespecified blood gene expression markers representing a composite of inflammation, interferon response, and immunoglobulin expression. Coming into the study, investigators hypothesized that MBSR would modulate systemic and central nervous system inflammation through top-down neurocognitive control over forebrain limbic areas responsible for the neurobiological stress response.

Prior to adjustment, no pre-post changes were noted in average hair cortisol, structural MRI, or CTRA as related to completion of MBSR. In mixed-effect analyses adjusting for age, race, body mass index, medical therapy, and time, changes in inflammatory gene expression (CTRA; n = 12) correlated inversely with changes in patient-reported stress (P <.0001), loneliness (P = .002), hair cortisol (P = .01), and aspects of interoceptive awareness. In similar exploratory mixed-effect regression with parcellated MRI data, a higher CTRA was associated with larger left (P = .02) and smaller right (P = .02) anterior insula cortical thickness.

Certain Factors May Assist in Predicting Clinical Phenotype Following Optic Neuritis

New research has suggested that several factors at the time of initial presentation of optic neuritis (ON) are associated with specific clinical phenotypes, and may help predict which neuroimmunological condition a patient will develop. Ultimately, utilizing these early predictors in clinical practice could better inform prognosis and management decisions, the study investigators noted.⁴

The trial aimed to determine final clinical phenotypes of either idiopathic ON, multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), myelin oligodendrocyte antibody disease (MOGAD) or secondary ON in a cohort of 64 individuals who presented with an initial, isolated attack of ON. Led by Hesham Abboud, MD, associate professor, Case Western Reserve University, univariate analyses on age, gender, race, laterality, visual acuity, relative afferent pulpillary defect, red desaturation, optical coherence tomography (OCT), fundoscopy, MRI, recovery, steroid response, need for plasma exchange (PLEX), and visual improvement were carried out to determine predictors of the final clinical phenotype.

The trial featured mostly females (78.1%), with an average age of onset of 41.3 (SD, 13.3) years and time to final diagnosis of 8.3 months. MS, the final phenotype in 22 individuals (34%), was associated with White race, unilateral ON, short segment hyperintensity on orbital MRI, and not receiving PLEX.

Following MS, the final phenotypes were idiopathic ON (n = 14; 22%), MOGAD (n = 11; 17%), NMOSD (n = 10; 16%), and secondary ON (n = 7; 11%). Findings showed that older age, poor steroid responsiveness, and receiving PLEX was associated with NMOSD, while Black race, bilateral ON, papillitis on fundoscopy, and long-segment hyperintensity on orbital MRI was associated with NMOSD. As for idiopathic ON, factors such as normal or thinned retinal nerve fiber layer on OCT and short-segment hyperintensity on orbital MRI were associated with final clinical phenotype. Of note, the initial visual acuity did not differentiate among final phenotypes at the time of initial presentation.

Positive Long-Term Safety, Low Discontinuation Rates Seen With Vidofludimus Calcium

Data from the open-label extension of the phase 2 EMPhASIS trial (NCT03846219) showed that treatment with vidofludimus calcium (Immunic), an investigational agent in development for MS, was safe and tolerable, with some patients staying on the therapy for more than 4 years.⁵

Vidofludimus calcium, or IMU-838, is a highly selective oral second-generation dhydroorotate dehydrogenase inhibitor designed to potentially provide broad-spectrum antiviral activity against different pathogenic viruses, including Epstein-Barr virus, which has been considered essential for onset of MS. In total, 254 individuals with relapsing-remitting MS completed the 24-week, double blind treatment period, and 209 remained on OLE treatment where they received either 30 or 45 mg of IMU-838 once daily.

In the study, 193 patients received at least 96 weeks of treatment and 144 were treated for at least 144 weeks. Notably, there was a low discontinuation rate, with 5.3% of patients dropping out. Of note, 4 treatment-emergent adverse events (TEAEs) led to treatment discontinuation.

In the OLE, the most common TEAEs were COVID-19 (9.1%), nasopharyngitis (4.7%), back pain (2.8%), and urinary tract infection (2.0%). Investigators recorded rates of 0.023 and 0.015 per treatment year for renal and liver TEAEs, respectively. Throughout the OLE, 14 serious AEs were reported, yielding a rate of 0.027 per patient per treatment year; however, none were considered to be related to the study drug. Additionally, no new safety signals were observed and no signal for changes in hematology parameters were seen.

REFERENCES
1. Chase E, Lane MA, Srikanth P, et al. Randomized, controlled trial of low-fat diet for fatigue in multiple sclerosis. Presented at: 2023 CMSC Annual Meeting; held May 31-June 3; Aurora, CO. Abstract DMX02
2. Alvarez E, Robertson D, Wynn D, et al. Ublituximab is associated with significant improvement in fatigue: results from ULTIMATE 1 and II. Presented at: 2023 CMSC Annual Meeting; May 31-June 3; Aurora, CO. Abstract DMT02
3. Hemond CC, Deshpande M, Morales IB, Slavich GM, Cole SW. An unblinded observational study of mildfulness-based stress reduction in MS: MRI and biological inflammatory correlates of patient-reported outcomes. Presented at: 2023 CMSC Annual Meeting; May 31-June 3; Aurora, CO. Abstract IMG06.
4. Sarin S, Modak N, Sun R, et al. Predicting the final clinical phenotype after the first attack of optic neuritis. Presented at: 2023 CMSC Annual Meeting; May 31 to June 3; Aurora, CO. Abstract NID13
5. Fox RJ, Wolf C, ONdrus M, Sciacca V, Muehler A. Assessment of long-term safety and tolerability of vidofludimus calcium in patients with relapsing-remitting multiple sclerosis in the open-label extension period of the phase 2 trial (EMPhASIS). Presented at: 2023 CMSC Annual Meeting; May 31 to June 3; Aurora, CO. Abstract DMT51