Ublituximab versus Teriflunomide in Relapsing Multiple Sclerosis

Ublituximab: A Novel Anti-CD20 Therapy for Multiple Sclerosis

“…20 Subsequently, the identical ULTIMATE I and ULTIMATE II phase III trials evaluating the use of ublituximab for the treatment of relapsing MS were undertaken. 6 These studies were randomized, double blind, multicentre and active-comparator controlled with teriflunomide. Key inclusion criteria were typical for relapsing MS studies and included:…”

“…Patients received antihistamine and corticosteroid premedication 30-60 minutes prior to infusions. 6 Together, the ULTIMATE studies randomized 1,089 patients, 543 to ublituximab (271 in ULTIMATE I and 272 in ULTIMATE II) and 546 to teriflunomide (274 in ULTIMATE I and 272 in ULTIMATE II). Baseline demographics were well balanced between the studies and the treatment groups.…”

“…Overall, 64.2% of the participants were women and 98.0% were white, with 56.7% being treatment-naïve before starting the study. 6 The primary endpoint was ARR at Week 96, for which ublituximab outperformed teriflunomide with an ARR of 0.08 versus 0.19 (rate ratio 0.41; 95% confidence interval [CI] 0.27 to 0.62; p<0.001) and 0.09 versus 0.18 (0.51; 95% CI 0.33 to 0.78; p=0.002) for reduction in clinical relapses of 59% and 49%, respectively, in ULTIMATE I and II. 6 This effect extended to secondary radiographic measures, including the total number of contrast-enhancing lesions, with reductions in the ublituximab group of 97% and 96% (0.02 versus 0.49 [rate ratio 0.03; 95% CI 0.02 to 0.06; p<0.001] and 0.01 versus 0.25 [rate ratio 0.04; 95% CI 0.02 to 0.06; p<0.001]), respectively, in ULTIMATE I and II.…”

“…2 There are currently two anti-CD20 DMTs, ocrelizumab and ofatumumab, approved for the treatment of relapsing MS by the US Food and Drug Administration (FDA), with ocrelizumab also indicated for the treatment of primary progressive MS. 3,4 These drugs also comprise the approved B-cell-directed DMTs, although their fellow anti-CD20 monoclonal antibody rituximab has been used extensively off-label. 5 Ublituximab is a novel anti-CD20 monoclonal antibody that has recently completed the identical phase III ULTIMATE I and ULTIMATE II trials for relapsing MS. 6 A literature search for English language articles and abstracts using the term 'ublituximab' was conducted on PubMed without date restrictions. The focus of this article is to provide a contextual overview of ublituximab's pharmacology, review the available clinical data, and discuss the future considerations for its use as a DMT.…”

All anti-CD20 monoclonal antibodies have similar efficacy and safety risks: Yes

“…However, the choice of comparator influences the ARR ratio, and because not all trials used the same comparator, the comparison of the ARR ratios across trials is limited. Nonetheless, the ASCLEPIOS trials with ofatumumab and the ULTIMATE trials 6 with ublituximab used teriflunomide as the same active comparator. Furthermore, both studies used twinned clinical trial designs with non-overlapping MS centers but identical protocols to ensure that observations made in one study would be replicated in a second independent dataset.…”