Ublituximab (Briumvi; TG Therapeutics, Morrisville, NC) treatment was associated with lower relapse rates and lower MRI disease activity than teriflunomide (Aubagio; Sanofi, Bridgewater, NJ) in treatment-naïve participants with relapsing multiple sclerosis (RMS), according to pooled post hoc subpopulation analyses of the phase 3 ULTIMATE I (NCT03277261) and II (NCT03277248) trials published in Frontiers in Immunology.

Investigators analyzed 96-week outcomes from participants in ULTIMATE I and ULTIMATE II, 2 identically designed, randomized, double-blind, active-controlled studies comparing ublituximab with teriflunomide in adults with RMS. The post hoc analysis included a treatment-naïve population, defined as participants who had not received an approved disease-modifying therapy (DMT) in the 5 years before enrollment, as well as an early treatment subpopulation of treatment-naïve participants whose first MS symptom occurred within 3 years before enrollment.

Key results include the following:

  • In the treatment-naïve population, annualized relapse rate was 0.081 with ublituximab compared with 0.188 with teriflunomide, representing a 56.7% relative reduction (P<.001).
  • In the early treatment subpopulation, annualized relapse rate was 0.130 with ublituximab compared with 0.334 with teriflunomide, a 61.0% relative reduction (P=.004).
  • Twelve-week confirmed disability improvement occurred in 10.7% of ublituximab-treated participants and 5.3% of teriflunomide-treated participants in the treatment-naïve population (P=.010).
  • In the early treatment subpopulation, 12-week confirmed disability improvement occurred in 14.4% of participants receiving ublituximab compared with 3.6% receiving teriflunomide (P=.002).
  • Gadolinium-enhancing T1 lesions were reduced by 96.1% with ublituximab versus teriflunomide in the treatment-naïve population and by 95.0% in the early treatment subpopulation.
  • New or enlarging T2 lesions were reduced by 90.6% and 91.6% with ublituximab versus teriflunomide in the treatment-naïve and early treatment populations, respectively.
  • NEDA-3 rates at weeks 24 to 96 were higher with ublituximab than teriflunomide in both the treatment-naïve population (82.7% vs 23.1%; P<.001) and early treatment subpopulation (80.5% vs 23.8%; P<.001).

Rates of 12-week confirmed disability progression were low in both treatment groups and did not differ significantly. The authors noted that the findings support the efficacy of ublituximab in treatment-naïve participants and in those treated within 3 years of symptom onset. Limitations include the post hoc design, smaller sample size in the early treatment subpopulation, low event rates for some disability outcomes, and nominal statistical testing without multiplicity adjustment.

Source: Robertson D, Alvarez E, Steinman L, et al. Disease outcomes with ublituximab in treatment-naïve participants: subpopulation analyses of the phase 3 ULTIMATE I and II studies in participants with relapsing multiple sclerosis. Front Immunol. 2026;17:1771848. doi:10.3389/fimmu.2026.1771848