DMT23
Infusion-Related Reactions with Ublituximab in the Phase 3 Ultimate I and II Studies in Relapsing Multiple Sclerosis

Thursday, June 2, 2022
Prince George's Exhibit Hall (Gaylord National Resort & Convention Center)
Edward J Fox, MD, PhD , Central Texas Neurology Consultants, Round Rock, TX
Lawrence Steinman, MD , Beckman Center for Molecular Medicine, Stanford University Medical Center, Stanford, CA
Hans-Peter Hartung, MD , Heinrich Heine University, Dusseldorf, Germany, Department of Neurology, Medical University of Vienna, Vienna, Austria, Department of Neurology, Palacky University, Olomouc, Czech Republic, Brain and Mind Centre, University of Sydney, Sydney, Australia
Enrique Alvarez, MD, PhD , University of Colorado, Aurora, CO
Peiqing Qian, MD , Swedish Medical Center, Seattle, WA
Sibyl Wray, MD , Hope Neurology MS center, Knoxville, TN
Derrick Robertson, MD , University of South Florida, Tampa, FL
DeRen Huang, MD, PhD , Center for Multiple Sclerosis, Mount Carmel Health System, Westerville, OH
Krysztof Selmaj, MD, PhD , Center of Neurology, Lodz, Poland, Department of Neurology, University of Warmia & Mazury, Olsztyn, Poland
Daniel Wynn, MD , Consultants in Neurology MS Center, Northbrook, IL
Koby Mok, PhD , TG Therapeutics, New York, NY
Denise Campagnolo, MD , TG Therapeutics Inc, New York, NY
Bruce A Cree, MD, PhD, MAS , UCSF Weill Institute for Neurosciences, Department of Neurology, University of California San Francisco, San Francisco, CA
PDF


Background: Ublituximab, a novel monoclonal antibody targeting a unique epitope on the CD20 antigen, is glycoengineered for enhanced antibody-dependent cellular cytotoxicity and administered in 1-hour maintenance infusions after the first infusion. In the ULTIMATE I and II studies in patients with relapsing multiple sclerosis (RMS), ublituximab met its primary endpoint of significantly reduced annualized relapse rate vs teriflunomide.

Objectives: To characterize frequency, severity, and type of infusion-related reactions (IRRs) with ublituximab.

Methods: ULTIMATE I (N=549) and II (N=545) evaluated ublituximab 450 mg intravenous (IV) 1-hour infusion every 24 weeks (following Day 1 infusion of 150 mg and Day 15 infusion of 450 mg) or teriflunomide 14 mg oral once daily for 96 weeks in patients with RMS. The teriflunomide group received placebo infusions; the ublituximab group received oral placebo. Participants received antihistamine and corticosteroid premedication (oral IV, or intramuscular [IM] at investigator discretion) 30-60 minutes prior to ublituximab/placebo infusions. Pooled IRR data from both trials were analyzed.

Results: Across ULTIMATE studies, the total number of infusions was 2644 for ublituximab and 2637 for placebo. Overall, 96.6% of ublituximab infusions were completed without interruption. The proportion of patients with IRRs was 47.7% and 12.2% in the ublituximab and placebo infusion groups, respectively. The proportion of ublituximab-treated patients experiencing an IRR during the first infusion was 43.3%, with the frequency of IRRs markedly decreasing during subsequent infusions. Of ublituximab patients with an IRR, 67.7% had 1 IRR only; of these patients, 93.2% experienced the IRR at first dose. Most IRRs in the ublituximab group were mild to moderate. One patient experienced a Grade 4 IRR (anaphylaxis) with ublituximab at the Day 15 infusion (drug interrupted/withdrawn). The proportion of ublituximab patients with pyrexia, chills, headache, and influenza-like illness was 9.5%, 7.9%, 7.5%, and 5.9%, respectively. Six patients discontinued ublituximab due to an IRR. IRR incidence in ublituximab patients receiving oral, IV, IM, and mixed oral/IV/IM premedication will be presented.

Conclusions: IRRs were the prevailing adverse event with ublituximab in ULTIMATE I and II; the majority occurred at the first dose and had minimal impact on infusion completion.

See more of: Disease-Modifying Therapy
See more of: Posters
<< Previous Abstract | Next Abstract >>