Ofatumumab, a fully human anti-CD20 monoclonal antibody, previously demonstrated superior efficacy versus teriflunomide in the phase 3 ASCLEPIOS I/II trials in people with relapsing multiple sclerosis (PwRMS).¹ Earlier data had shown that ofatumumab maintained a favorable safety profile and sustained efficacy over 6 years of treatment.¹ At the AAN Annual Meeting 2025, Dr. Gabriel Pardo from the Oklahoma Medical Research Foundation presented updated findings on the long-term safety and disability outcomes associated with continuous ofatumumab treatment for up to 7 years.¹ The analysis also explored the impact of early versus delayed ofatumumab initiation, including outcomes in recently diagnosed (≤3 years) and treatment-naïve (RDTN) patients.¹

This updated analysis included participants who received at least 1 dose of ofatumumab in ASCLEPIOS I/II, APOLITOS, APLIOS, or the ALITHIOS extension study (overall safety population, n=1969), as well as participants from ASCLEPIOS I/II or ALITHIOS who comprised the RDTN subgroup (n=546).¹ Of the 1,882 participants in the efficacy population (OMB-OMB, n=946; TER-OMB, n=936), including 615 RDTN participants (OMB-OMB, n=314; TER-OMB, n=301), a total of 1,367 entered ALITHIOS (OMB-OMB, n=690; TER-OMB, n=677).¹

Key endpoints included safety outcomes (adverse events [AEs], serious infections, immunoglobulin levels, and mortality) and efficacy measures, such as the cumulative event rates of 3- and 6-month confirmed disability worsening (3/6mCDW), 3- and 6-month progression independent of relapse activity (3/6mPIRA), and 3- and 6-month relapse-associated worsening (3/6mRAW), evaluated up to 7 years.¹ At the data cutoff, 76.3% (1,043/1,367) of ALITHIOS participants had completed the 5-year extension period, with 944 entering a subsequent 3-year extension.¹ Approximately 22% had discontinued, mainly due to patient or guardian decision (9.6%) or adverse events (5.1%), while 24 participants remained ongoing.¹ Baseline characteristics were typical of the pwRMS population and were balanced across treatment groups.¹ Among the RDTN subgroup, 465 participants entered ALITHIOS; of these, 355 completed the 5-year extension, 321 proceeded to the 3-year extension, and 103 discontinued, with similar reasons for discontinuation (patient/guardian decision: 9.9%; adverse events: 5.6%).¹

Overall, the safety profile remained consistent with previous 6-year data, with no new safety signals identified.¹ Exposure-adjusted incidence rates of AEs, serious AEs, and infections remained low and stable across the overall and RDTN populations.¹ Regarding efficacy outcomes, nearly 8 in 10 pwRMS receiving continuous ofatumumab (OMB-OMB group) remained free from 6mCDW at 7 years (77.3% vs. 73.8%, p=0.069) for TER-OMB.¹ Among RDTN patients, first-line ofatumumab treatment was associated with even greater benefit, with 81.5% of participants free from 6mCDW compared to 74.3% in the TER-OMB group (p=0.031).¹ A significantly higher proportion of participants remained free from 3mCDW with continuous OMB-OMB compared with TER-OMB in the overall population (73.7% vs. 70.2%; p=0.036) and among RDTN participants receiving first-line therapy (79.3% vs. 71.3%; p=0.021).¹

Results for PIRA further reinforced the advantages of early and continuous ofatumumab treatment.¹ At 7 years, over 8 in 10 pwRMS treated continuously with ofatumumab were free from 6mPIRA (83.7% vs. 82.3% for TER-OMB), with even more pronounced benefits among RDTN participants (87.6% vs. 81.8%).¹ Although differences in 3mPIRA freedom were not statistically significant, numerically higher proportions were consistently observed in favor of the OMB-OMB group.¹ Additionally, the number of 3/6m RAW events in both the overall and RDTN subgroups remained low and consistent with the 6-year data.¹

In conclusion, these long-term data affirm the sustained, favorable benefit–risk profile of ofatumumab through 7 years of treatment and underscore the importance of early initiation.¹ Continuous first-line ofatumumab therapy was associated with significantly greater freedom from disability progression and numerically fewer PIRA events, supporting its role as a preferred early treatment option for PwRMSs.