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

Background Evidence suggests that treating relapsing multiple sclerosis (RMS) initially with a high-efficacy disease-modifying therapy (DMT) is superior to an escalating approach at reducing disability progression and relapse rate. Objectives To evaluate the efficacy of ublituximab versus teriflunomide in participants without prior DMT (treatment-naïve population) and in a subset of treatment-naïve participants with symptom onset ≤ three years (early treatment subpopulation). Methods Pooled post hoc analyses of ULTIMATE I/II were conducted at Week 96. Results The annualized relapse rate was 0.081 for ublituximab ( n = 345) versus 0.188 for teriflunomide ( n = 377) ( p < 0.001) in the treatment-naïve population and 0.130 for ublituximab ( n = 139) versus 0.334 for teriflunomide ( n = 140) in the early treatment subpopulation ( p = 0.004). Twelve-week confirmed disability improvement rates were 10.7% versus 5.3% ( p = 0.010) in the treatment-naïve population and 14.4% versus 3.6% ( p = 0.002) in the early treatment population (ublituximab vs. teriflunomide). Significant reductions in gadolinium-enhancing T1 lesions and new/enlarging T2 lesions, respectively, occurred for ublituximab versus teriflunomide (treatment naïve: 0.031 vs. 0.791 and 0.390 vs. 4.144; p < 0.001 for both; early treatment: 0.051 vs. 1.030 and 0.508 vs. 6.068; p < 0.001 for both). Conclusions Ublituximab was associated with significant treatment benefits at Week 96 in treatment-naïve participants and those receiving treatment within three years of symptom onset. Clinical trial registration https://clinicaltrials.gov/study/NCT03277261 and https://clinicaltrials.gov/study/NCT03277248 , identifiers NCT03277261 and NCT03277248.