Ublituximab Outperforms Teriflunomide in Improving Fatigue in Multiple Sclerosis

Enrique Alvarez, MD, PhD

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 multiple sclerosis (MS), resulted in greater improvements in fatigue in comparison with teriflunomide (Aubagio; Sanofi).

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). The data were presented by lead investigator Enrique Alvarez, MD, PhD, associate professor of neurology, University of Colorado School of Medicine, at the 2023 Consortium of Multiple Sclerosis Centers (CMSC) Annual Meeting, May 31 to June 3, in Aurora, Colorado.

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.

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Ublituximab gained FDA approval in December 2022 based on results from ULTIMATE 1 and 2, in which treatment with the agent resulted in significant reductions in annualized relapse rate for patients with relapsing MS. All told, investigators observed ARRs of 0.08 and 0.09 in UTLIMATE 1 and 2 at week 96, compared with rates of 0.19 and 0.18 for the teriflunomide-treated group in the respective studies (P <.001; P <.002). Ublituximab was associated with infusion-related reactions, though, which occurred in 47.75 of the treated participants compared with 12.2% of those on teriflunomide.

In the prespecified pooled analysis, 5.2% of those on ublituximab had worsening of disability confirmed at 12 weeks, compared with 5.9% of those in the teriflunomide group (hazard ratio [HR], 0.84; 95% CI, 0.50-1.41; P = .51). Worsening of disability confirmed at 24 weeks was found in 3.3% of ublituximab-treated patients vs 4.8% of teriflunomide-treated patients, but was not considered significant. In the prespecified pooled tertiary analysis that was not included in the hierarchical analysis and from which no conclusions can be drawn, 12.0% of the participants who received ublituximab had a lessening of disability confirmed at 12 weeks, as compared with 6.0% of the participants who received teriflunomide (HR, 2.16; 95% CI, 1.41 to 3.31).

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REFERENCES
1. 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
2. TG Therapeutics Announces FDA Approval of BRIUMVI™ (ublituximab-xiiy). News release. TG Therapeutics. December 28, 2022. Accessed May 31, 2023. https://ir.tgtherapeutics.com/news-releases/news-release-details/tg-therapeutics-announces-fda-approval-briumvitm-ublituximab