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

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 6(th) 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 5(th) 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 3(rd) 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.