Cognitive dysfunction in MS patients is common, with up to 65% of patients experiencing cognitive difficulties during the course of the disease. The effects of ocrelizumab on cognition have not been studied in a real-world setting.
We sought to determine the effects of ocrelizumab on cognition in patients with relapsing multiple sclerosis (MS) or active secondary progressive multiple sclerosis (aSPMS) using the CogEval app's Processing Speed Test (PST), a validated analogue of the Symbol Digit Modalities Test (SDMT). The PST has three major advantages over the SDMT: 1) PST takes only 2 minutes to complete, and does not require a healthcare professional to be present with the patient during testing, 2) PST has been shown to be more sensitive to T2 lesion volume compared to SDMT, and 3) There is a smaller learning effect with PST compared to SDMT.
We performed the PST on patients in our clinic currently receiving ocrelizumab or who were started on ocrelizumab from January 2019 to April 2020. Only patients who had received at least two doses of ocrelizumab and had at least 3 PST scores were included in the analysis. 28 patients met these criteria. Based on the average of subsequent PST tests performed (Range: 2-5) we analyzed the proportion of patients who improved on PST (>4 points) were stable (no change >4 points or <4 points) or worsened (< 4 points). We performed univariate regression analyses based on age (>40 and <40), gender, smoking, and educational attainment (four-year college degree vs. no college degree). We also performed a sub-group analysis on nine patients starting ocrelizumab therapy with a PST score prior to initiation of ocrelizumab.
Average time on treatment for the cohort was 430 days. 32.1% of patients showed improvement of their PST scores, 50% of patients had stable PST scores, and 17.9% of patients had a worsening of their PST scores. Univariate regression analyses were performed based on age, gender, smoking, and educational attainment (four-year college degree vs. no college degree) and there were no significant trends with any of these analyses. In the sub-group analysis of nine patients with a PST score prior to initiation of ocrelizumab, three patients showed improvement in their PST scores, four patients were stable, and two patients worsened.
To our knowledge, this is the first real-world analysis of the effects of ocrelizumab on cognition using the PST, a validated analogue of SDMT. A substantial majority of patients showed stability or improvement on PST during the course of their treatment with ocrelizumab. Univariate regression analyses looking at age, gender, smoking and educational attainment showed no significant trends, suggesting baseline demographics/disease characteristics did not affect the outcome of PST scores. Longer-term real-world analyses are necessary to determine the effects of prolonged B cell depletion on cognition in MS patients taking ocrelizumab.