New findings support ofatumumab as first-line therapy in early MS

A post-hoc analysis of the ASCLEPIOS I/II trials comparing ofatumumab with teriflunomide focused on newly diagnosed relapsing MS (RMS) patients with low disease activity. In this subgroup, ofatumumab was associated with >2-fold higher odds of remaining free of disease activity at 1 year and an 18-fold higher odds at 2 years [1].

The rationale for this post-hoc analysis was the well-documented evidence that early use of high-efficacy therapy is associated with less accrual of long-term disability [2–4]. In the phase 3 ASCLEPIOS I/II trials (NCT02792218/NCT02792231), the anti-CD20 monoclonal antibody ofatumumab demonstrated a favourable safety and superior efficacy versus teriflunomide in the overall RMS population, as well as in the recently diagnosed (≤3 years) and treatment-naïve subgroups [5,6]. Prof. Heinz Wiendl (University of Freiburg, Germany) presented the results from a subgroup analysis of 261 treatment-naïve patients with early MS and low disease activity, defined as no more than 1 relapse in the 2 years prior to enrolment. The primary efficacy endpoint was no evidence of disease activity (NEDA-3).

In year 1, the proportions achieving NEDA-3 were 43.9% with ofatumumab versus 28.9% with teriflunomide (OR 2.38). In year 2, these proportions were 89.9% versus 34.4%, respectively (OR 18.27).

Despite the low clinical disease activity, ofatumumab demonstrated a pronounced effect on MRI activity and neurofilament light (NfL) levels, and a trend toward a lower annualised relapse rate (ARR):

Adjusted number of gadolinium-enhancing (Gd+) T1 lesions: 0.02 versus 0.30 (RR 0.08; 95% CI 0.03–0.21; P<0.001).
Adjusted number of new or newly enlarging T2 lesions: 0.62 versus 3.59 (RR 0.17; 95% CI 0.12–0.26; P<0.001).
ARR: 0.07 versus 0.10 (RR 0.63; 95% CI 0.32–1.26; P=0.192).
Serum NfL levels: a relative reduction with ofatumumab of 20.4% in year 1 (P=0.258) and 15.2% in year 2 (P<0.001).

The safety of ofatumumab was consistent with that observed in the overall ASCLEPIOS I/II population. Adverse events occurred in 86.7% of patients in the ofatumumab group and 88.7% in the teriflunomide group. Rates of serious adverse events and serious infections were similar between groups (5.8% versus 7.1%).

Prof. Wiendl and colleagues concluded that these findings support the early use of ofatumumab as first-line therapy in RMS patients, even in the presence of low disease activity.

Wiendl H, et al. Efficacy and safety of ofatumumab in treatment-naive people with early RMS and low clinical disease activity. P134, ACTRIMS Congress 2026, 4–7 February, San Diego, California, USA.
Kappos L, et al. JAMA Neurol. 2020;77(9):1132–1140.
Lublin FD, et al. Brain. 2022;145(9):3147–3161.
He A, et al. Lancet Neurol. 2020;19(4):307–316.
Hauser SL, et al. N Engl J Med. 2020;383(6):546–557.
Gärtner J, et al. Mult Scler. 2022;28(10):1562–1575.