Ofatumumab boasts long-term safety in relapsing multiple sclerosis

Treatment with ofatumumab in the long term (approximately 3.5 years) among patients with relapsing multiple sclerosis (MS) is well-tolerated, with no new safety risks found, according to the results of ALITHIOS, presented at the 2022 Annual Meeting of the American Academy of Neurology.

“This additional safety data will help confirm ofatumumab’s longer-term safety profile and provide further confidence to the MS community,” the researchers said.

ALITHIOS, a phase IIIb, open-label study, sought to assess the long-term safety and tolerability of ofatumumab treatment in patients with relapsing MS. Patients who completed the core ASCLEPIOS I/II, APOLITOS, and APLIOS clinical trials were eligible to enter the umbrella extension trial.

Cumulative data for up to 4 years of ofatumumab treatment (data cutoff: 25 September 2021) in the overall (n=1,969), continuous (ofatumumab in core+extension; n=1,292), and newly switched groups (teriflunomide core and ofatumumab extension; n=677) were analysed.

The researchers evaluated the proportion of patients with treatment-emergent adverse events (AEs), serious AEs, serious infections (ie, opportunistic infections), and malignancies. They also examined laboratory parameters including neutrophils, lymphocytes, and serum immunoglobulin (Ig) G and IgM levels. [Hauser S, et al, AAN 2022]

At data cutoff of 29 January 2021, 1,650 (83.8 percent) experienced at least one AE (exposure-adjusted incidence rate [EAIR], 148.7) and 191 (9.7 percent) had one or more serious AEs (EAIR, 4.8); the incidence of serious infections (2.9 percent; EAIR, 1.4) and malignancies (0.6 percent; EAIR, 0.3) was low.

Mean serum IgG levels remained stable, while mean IgM levels decreased but remained above the lower limit of normal. Of note, reduced Ig levels did not correlate with serious infections.

“Updated safety data representing continuous ofatumumab treatment for up to 4 years will be presented, focusing on the incidence of serious infections including opportunistic infections, incidence of malignancies, and deaths,” the researchers said. “The long-term trend of IgG/IgM levels and their association with serious infections will also be investigated.”

Monthly injections

Of note, monthly ofatumumab subcutaneous injections were less burdensome for patients than other more frequent injections needed, such as with interferon-beta or glatiramer acetate. In addition, ofatumumab rarely induced flu-like symptoms, which were common with interferon-beta. [Mult Scler J 2022;doi: 10.1177/13524585221079731; Mult Scler J 2021;doi:10.1177/13524585211044479]

“These factors provide a plausible explanation for the high adherence observed with ofatumumab treatment (only two out of 1,882 [0.2 percent] patients discontinued from the treatment epoch owing to noncompliance),” the authors said. [PLoS ONE 2015;10:e0127960]

Another advantage of ofatumumab’s subcutaneous route was the convenience of self-administration at home, leading to potential cost-effectiveness benefits.

“One limitation of these new analyses is the lack of a comparator cohort,” the researchers said. “However, this is a common limitation of long-term studies and does not undermine the utility of data reported specifically for long-term safety follow-up.”