The matching-adjusted analysis compared separate trials, was funded by the drug’s European commercialisation partner, and is described by its authors as exploratory.
Written By: Aasritha Thippavajjala, PharmD
Reviewed By: Pharmacally Editorial Team
TG Therapeutics announced on October 12, 2026, the publication of a five-year matching-adjusted indirect comparison (MAIC) evaluating BRIUMVI (ublituximab-xiiy) against ocrelizumab and ofatumumab in relapsing multiple sclerosis (RMS). Published online in Multiple Sclerosis and Related Disorders, the analysis associated BRIUMVI with a lower estimated hazard of 24-week confirmed disability progression (CDP24) than either comparator. The findings are exploratory and do not establish comparative superiority because the therapies were not evaluated in a head-to-head trial.
How the comparison was conducted
The analysis used individual patient data from 545 participants in the Phase 3 ULTIMATE I and II trials and their open-label extension (NCT03277261, NCT03277248, NCT04130997). These data were compared with published aggregate results from the Phase 3 OPERA I/II trials of ocrelizumab and ASCLEPIOS I/II trials of ofatumumab. One ublituximab participant was excluded because baseline matching information was missing, leaving 544 participants for the analysis.
Investigators reweighted the ublituximab data separately for each comparison to align available baseline characteristics with those reported for the comparator populations. Characteristics included age, sex, Expanded Disability Status Scale (EDSS) score, MRI lesion measures, prior relapse activity and time since diagnosis, where corresponding data were available. For time-to-event analyses, comparator patient-level data were reconstructed from digitised Kaplan–Meier curves and numbers at risk. Weighting can improve balance in measured characteristics, but it cannot remove bias from unmeasured differences between trials.
The analysis was unanchored. The ocrelizumab trials used interferon beta-1a as a comparator, while the ublituximab and ofatumumab programmes used teriflunomide. As there was no single common comparator across all three treatment programmes, the analysis relied on stronger assumptions than an anchored indirect comparison. The authors described the post hoc analysis as exploratory.
Disability-progression estimates
The adjusted hazard ratio for CDP24 was 0.560 (95% confidence interval [CI] 0.380–0.826) versus ocrelizumab and 0.509 (95% CI 0.350–0.741) versus ofatumumab. These estimates correspond to 44.0% and 49.1% lower relative hazards, respectively. A hazard reduction describes the relative rate of events over time, not the percentage of patients who avoided progression.
At 240 weeks, estimated cumulative CDP24 was 9.3% with ublituximab versus 16.1% with ocrelizumab, and 9.4% versus 17.9% with ofatumumab. The slightly different ublituximab estimates reflect the separate weighting used for each comparison.
Because proportional hazards may not hold over long follow-up, the authors also assessed restricted mean survival time (RMST) through 240 weeks. The model estimated 8.1 additional weeks free from confirmed progression versus ocrelizumab (95% bootstrap CI 2.3–14.1) and 13.1 additional weeks versus ofatumumab (95% CI 6.7–19.3). Both confidence intervals excluded zero. These are model-based estimates derived from weighted and reconstructed data, not observed differences from a randomized head-to-head trial.
Relapse activity
The MAIC-adjusted annualized relapse rate (ARR) for ublituximab declined from 0.118 in Year 1 to 0.032 in Year 5 in the comparison with ocrelizumab, and from 0.116 to 0.030 in the comparison with ofatumumab. Published ARR estimates for ocrelizumab were 0.140 in Year 1 and 0.070 in Year 5; corresponding estimates for ofatumumab were 0.128 and 0.034.
The estimates were not uniformly lower for ublituximab across all years. In Year 3, for example, the estimated ARR was 0.054 for ublituximab and 0.053 for ofatumumab. Comparator variance estimates were not consistently reported, preventing formal statistical comparisons of the long-term ARR estimates.
Limitations and funding
An unanchored MAIC assumes that all relevant prognostic factors and treatment-effect modifiers have been measured and appropriately adjusted for. Prior disease-modifying therapy and detailed MRI burden were not consistently reported and could not be included, leaving potential for residual confounding. The analysis also did not model comparator dropout, treatment switching or selection into extension phases. A sensitivity check applying the ASCLEPIOS-matched weights to the ULTIMATE teriflunomide arm produced an ARR ratio of 0.86 (95% CI 0.68–1.05) against published ASCLEPIOS teriflunomide results. The authors described this as partial validation.
Neuraxpharm, TG Therapeutics’ European commercialisation partner for BRIUMVI, funded the study. Optimax Access Ltd conducted the analyses; two authors were Optimax employees and one was affiliated with Neuraxpharm. TG Therapeutics and Neuraxpharm supplied the ULTIMATE data.
Interpretation
The analysis suggests directionally favourable five-year estimates for BRIUMVI on disability progression and relapse activity, but its unanchored design, reliance on published comparator data and potential residual confounding limit causal interpretation. The findings should be considered exploratory and complementary to randomized trial evidence, pending confirmation in direct comparative studies or robust real-world analyses.
References
TG Therapeutics Announces Publication of Five-Year Comparative Analysis of BRIUMVI Versus Ocrelizumab and Ofatumumab in Relapsing Multiple Sclerosis 12 October 2026
Gold R, Ansaripour A, Schmierer K et al, Long-Term Comparative Outcomes in Relapse Activity and Disability Progression Among Anti-CD20 Therapies in Relapsing Multiple Sclerosis: An Unanchored Matching-Adjusted Indirect Comparison, Multiple Sclerosis and Related Disorders, 2026; 115, https://doi.org/10.1016/j.msard.2026.107953
Study to Assess the Efficacy and Safety of Ublituximab in Participants with Relapsing Forms of Multiple Sclerosis (RMS) (ULTIMATE 1), NCT03277261
Study to Assess the Efficacy and Safety of Ublituximab in Participants with Relapsing Forms of Multiple Sclerosis (RMS) (ULTIMATE II), NCT03277248
An Extension Study of Ublituximab in Participants with Relapsing Multiple Sclerosis, NCT04130997
About the Writer
Aasritha Thippavajjala (Linkedin) is a pharm D student and aspiring medical writer with medical writing, clinical training experience and a strong interest in clinical research and patient safety She has hands-on exposure to clinical pharmacy activities including medication profile assessment, clinical case review, identification of potential drug-related problems, ADR awareness, patient counselling, and clinical documentation. She has also gained experience in medical literature review, evidence synthesis, and scientific communication through her published review article on digital twin-based patient simulation and her poster presentation at the 74th Indian Pharmaceutical Congress. Certified in ICH Good Clinical Practice (E6(R3)) and Scientific Writing in Health Research, she is passionate about applying her clinical knowledge and research skills to medical writing ,clinical research and contributing to accurate, evidence-based healthcare.