Ocrelizumab (OCR), an anti-CD20 antibody, was approved in the US in March 2017 for treating relapsing (RMS) and primary progressive MS (PPMS). Infections were more commonly seen in patients receiving OCR in earlier trials. Last year European Medicines Agency updated the OCR prescribing information to include the association between a reduction in immunoglobulins especially IgG and serious infections.
To determine if there is a relationship in baseline and follow up immunoglobulins levels and the risk of having an infection
MS patients in our OCR registry with at least one IgM/IgG value and who received ≥2 doses of OCR were included. IgG/IgM levels were obtained within a month of each infusion. Wilcoxon rank-sum tests and linear models were used to examine the relationships between IgM/IgG and infections.
337 patients were included. 72.4% were female; median age was 53.2 [IQR = 19.8] years with a median disease duration of 13.5 [IQR = 11.8] years. 78% had RMS, 13.4% had SPMS, and 8.6% had PPMS. 27% of patients were treatment naïve. Median time on OCR was 26 [IQR = 8.9] months. 88.7% of patients had more than one IgG and IgM value. Infections were seen in 226 (67.1%) patients. The median age of patients who did and did not have an infection was 53.5 [IQR =20.2] and 53 [IQR = 18.1] respectively. Prior natalizumab use was associated with a higher rate of infection, 46 of 62 (74%). No significant differences were found between IgM levels nor IgG levels for cases of infection (56 [IQR = 53], 792 [IQR = 294.5] mg/dL) and non-infection (52 [IQR = 51], 828.5 [IQR = 310.2]) mg/dL) (
Older patients with longer duration of disease and OCR therapy have been found to have more infections, but we did not observe age as a risk factor for infection in this cohort. Furthermore, neither baseline nor follow up IgM or IgG levels predicted infections in this study. However, the median time on OCR was a little over 2 years which may be too soon to see a difference in the rate of infection and immunoglobulin levels.