Ofatumumab improves cognitive processing speed

In the phase 3 ASCLEPIOS I/II trials, ofatumumab was associated with more clinically meaningful improvements in cognitive processing speed (CPS) compared with teriflunomide, as measured by changes in Symbol Digit Modalities Test (SDMT) scores. This was observed in the overall population and in the subgroup of patients recently diagnosed with multiple sclerosis (MS).

Cognitive impairment presents in 40–70% of MS patients, can start early in the disease course, and can have a profoundly negative effects on quality-of-life. Cognitive impairment, particularly CPS, also seems to be able to predict MS progression. In trials, CPS is often measured with the SDMT. Early baseline screening with the SMDT or a similar validated test is recommended for clinically stable patients. The phase 3 ASCLEPIOS I and II trials (NCT02792231, NCT02792218), using the SDMT, showed that ofatumumab significantly reduced inflammatory disease activity, relapses, and delayed disability worsening compared with teriflunomide in patients with relapsing MS. A subanalysis, presented by Prof. Ralph H.B. Benedict (University at Buffalo, NY, USA), assessed the effect in the overall populations of ofatumumab (n=946) versus teriflunomide (n=936) on SDMT performance. A ≥4-point improvement (or a ≥10% change) in SDMT score is considered to be clinically meaningful. A recent diagnosis was defined as diagnosed within the last 3 years.

Ofatumumab significantly improved SDMT scores from baseline to month 24 in the overall group; improvement was even more pronounced in the recently diagnosed subgroups (see Figure) [1]. More patients on ofatumumab had ≥4-point sustained improvement on SDMT (25%) versus teriflunomide (19.6%) in the overall group; there was a similar pattern in the recently diagnosed group (26.9% and 20.2%, respectively). Ofatumumab increased the probability of time-to-first 6-month confirmed cognitive improvement in the overall population (HR 1.14; 95% CI 0.96–1.36), in the recently diagnosed subgroup (HR 1.19; 95% CI 0.93–1.52), and in the group without baseline cognitive impairment (HR 1.23; 95% CI 0.98– 1.56). The observed trends for greater benefits of ofatumumab in those without cognitive impairment at baseline and in the recently diagnoses population provides further support for initiating a high-efficacy therapy early in the disease course to preserve cognitive function.

Figure: Change from baseline in SDMT score of ofatumumab versus teriflunomide for overall and recently diagnosed patient populations [1]



SDMT, Symbol Digit Modalities Test; M, month.

At the same session, Prof. Francesco Saccà (University of Naples Federico II, Italy) presented cumulative data for up to 4 years that indicated that longer-term safety of ofatumumab is good, with no new safety risks identified [2]. Adverse events and serious adverse events remained consistent with observations in the phase 3 trials. The rate of serious infections remained stable, as did the mean levels of immunoglobulin. Most reported cases of COVID-19 were not serious (90.2%) and most patients (98.4%) recovered. The risk of malignancies was not increased over time.

1. Benedict RHB, et al. Improvement in Cognitive Processing Speed with Ofatumumab in Patients with Relapsing Multiple Sclerosis. OPR-130, EAN 2022, 25–28 April, Vienna, Austria.
2. Saccà F, et al. Longer-term Safety of Ofatumumab in Patients With Relapsing Multiple Sclerosis. OPR-134, EAN 2022, 25–28 April, Vienna, Austria.

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Posted on 22 August 2022