Hypogammaglobulinemia, infections and COVID-19 in people with multiple sclerosis treated with ocrelizumab.

ABSTRACT

OBJECTIVE: To determine the influence of immunoglobulins (Ig) level on the rate of infections in people with multiple sclerosis (pwMS) treated with ocrelizumab. METHODS: We enrolled 109 consecutive pwMS treated with ocrelizumab with a mean follow-up of 2.69±0.56 (1.36-4.27) years. We have retrospectively searched our electronic database and the following information was collected age, sex, MS characteristics, number of ocrelizumab cycles, infections, duration of the infection, hospitalization due to infection, treatment of the infection, and COVID-19 characteristics. Ig levels were measured within 14 days before each ocrelizumab infusion. RESULTS: Number of pwMS with values of IgM and IgG below lower level of normal at baseline was 3 (2.8%) and 2 (2.8%), respectively; and before 6th cycle of ocrelizumab 5 (13.5%) and 5 (13.5%), respectively. Levels of IgM were steadily decreasing over time, while levels of IgG started to show statistically significant drop only after 5th cycle of ocrelizumab. 58.7% pwMS experienced infection during treatment, with a median number of infections per pwMS being 1, range 0-4. Female sex increased the risk of any infection (HR 2.561, 95%CI 1.382-4.774, p=0.003). Higher age and smaller drop in IgM before 3rd ocrelizumab cycle increased the risk for infection requiring hospitalization (HR 1.086, 95%CI 1.018-1.159, p=0.013 and HR 9.216, 95%CI 1.124-75.558, p=0.039, respectively). Longer disease duration increased the risk for COVID-19 (HR 1.075, 95%CI 1.002-1.154, p=0.045). CONCLUSION: The present findings broaden limited real-world data on infection and COVID-19 risk in pwMS treated with ocrelizumab.