Ublituximab is associated with a lower annualized relapse rate (ARR) and fewer new or enlarging brain lesions among patients with relapsing multiple sclerosis (MS) compared with teriflunomide. These are the findings of a study published in The New England Journal of Medicine.
Previous studies have indicated that monoclonal antibodies targeting the activity of B cells are efficacious for MS. Ublituximab is a type 1 chimeric immunoglobulin (Ig)G1 monoclonal antibody which targets the B cell cluster of differentiate 20 (CD20) antigen.
For this analysis, data from the identically designed phase 3 multicenter, double-blind, double-dummy, randomized, active-controlled studies ULTIMATE I (Clinicaltrials.gov Identifier: NCT03277261) and ULTIMATE II (Clinicaltrials.gov Identifier: NCT03277248) conducted between 2017 and 2018 at 104 sites in 10 countries were analyzed for the safety and efficacy of intravenous ublituximab in patients with relapsing MS compared with teriflunomide.
Patients with relapsing MS were randomized in a 1:1 ratio to receive 150 mg intravenous ublituximab on day 1 followed by 450 mg ublituximab on days 15, 24, 48, and 72 with oral placebo for 96 weeks (trial I, n=271; trial II, n=272) or 14 mg oral teriflunomide through week 96 with intravenous placebo on the same schedule (trial I, n=274; trial II, n=272). The primary efficacy outcome was the ARR.
The study cohorts comprised:
- 61.3%-65.4% women; aged mean, 34.5-37.0 years; 97.1%-98.9% were White
- 97.4%-98.5% had relapsing remitting MS
- 50.7%-59.8% had received no prior disease-modifying therapy
- The average number of relapses in the previous 24 months was 1.8-2.0
- 48.2%-57.4% had no magnetic resonance imaging (MRI) lesions at baseline
- The average number of MRI lesions was 1.6-2.6
Compared with teriflunomide, the ARR was over 96 weeks for ublituximab was 0.08 and 0.19 in trial I (rate ratio [RR], 0.41; 95% CI, 0.27-0.62; P <.001) vs 0.09 and 0.18 in trial II (RR, 0.51; 95% CI, 0.33-0.78; P =.002). The mean number of gadolinium-enhancing lesions per magnetic resonance imaging (MRI) scan was 0.02 in the ublituximab group and 0.49 in the teriflunomide group in trial I (RR, 0.03; 95% CI, 0.02-0.06; P <.001) and 0.01 and 0.25, respectively, (RR, 0.04; 95% CI, 0.02-0.06; P <.001) in trial II.
No significant group differences were observed for disability related end points in either trial alone or in the pooled analysis.
Overall, CD19+ B cell counts decreased by 96% after the first ublituximab dose compared with 53% after the first teriflunomide dose. At the end of the double-blind period, the rates of CD19+ B cell counts had decreased by 97% and 18% among the ublituximab and teriflunomide recipients, respectively.
In the pooled analysis of the 2 trials, 89.2% of individuals who received ublituximab and 91.4% of individuals who received teriflunomide reported at least 1 adverse event. Grade 3 or higher adverse events were reported by 21.3% of individuals and 14.1% of individuals in the ublituximab and teriflunomide groups, respectively. The most common events were infusion-related reactions (47.7%), headache (34.3%), and nasopharyngitis (18.3%) in the ublituximab cohort and headache (26.6%), nasopharyngitis (17.9%), and alopecia (15.3%) in the teriflunomide group.
The researchers noted that “Ublituximab was associated with infusion-related reactions.”
“Larger and longer trials are required to determine the efficacy and safety of ublituximab in patients with relapsing multiple sclerosis, including comparison with other disease-modifying treatments such as existing anti-CD20 monoclonal antibodies,” the researchers concluded.
The major limitation of these trials was not comparing ublituximab against other therapies which are more potent than teriflunomide for the treatment of MS.
Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.
Steinman L, Fox E, Hartung H-P, et al. Ublituximab versus teriflunomide in relapsing Multiple Sclerosis. N Engl J Med. Published online August 25, 2022. doi:10.1056/NEJMoa2201904