The ULTIMATE trials: are there advantages of ublituximab over teriflunomide in relapsing multiple sclerosis?

The involvement of B-cells in multiple sclerosis has only recently emerged. Ublituximab is a monoclonal antibody that binds to the B-cell antigen CD20 with enhanced B-cell targeting.

This evaluation is of the identical ULTIMATE (UbLiTuximab In Multiple Sclerosis Treatment Effects) I and II trials comparing ublituximab (TG-1101) and teriflunomide in relapsing multiple sclerosis. The primary efficacy end point was the annualized relapse rate and was lower in the ublituximab than the teriflunomide group.

The continuation rates to oral teriflunomide in ULTIMATE were higher than in other trials, possibly because of the supervised double-dummy protocol used with intravenous ublituximab. This may have contributed to the higher efficacy with teriflunomide in this trial than previously reported. Nevertheless, ublituximab was more effective than teriflunomide at reducing the annualized relapse rates and MRI endpoints, but not for no evidence of disease activity (NEDA). Subsequently, a meta-analysis of the ULTIMATE trials did show that ublituximab was superior to teriflunomide in NEDA. Long-term studies of the adverse effects of ublituximab are required. Despite the positive results from ULTIMATE for ublituximab, it is still under the scrutiny of the Food and Drug Administration (FDA), and conclusions should await their findings.