Ocrelizumab (OCR) is a humanized anti-CD20 monoclonal antibody used in the treatment of MS. The drug targets CD20 and acts to reduce circulating B cells. Infection is a known adverse effect of treatment. It is not a requirement of the licence to monitor the effect of OCR on B cells counts and the relationship between B cell count and adverse effects is unknown.
We aimed to assess the impact of OCR infusions on B cell counts in our patient group and whether there is a relationship between B cell count & adverse events such as infusion reactions or infections
Lymphocyte subsets were measured for each patient at baseline and before each subsequent infusion. Patients who had received OCR were identified from hospital records & lymphocyte subset results obtained from pathology reports. Date of infusions were noted and B cell data was correlated to determine average counts before or after each dose. Patient records were examined retrospectively to identify reports of adverse events including infection. These were then related to the degree of B cell suppression.
170 people with MS (pwMS) received infusions of ocrelizumab from Sept 2018 to March 2020. Baseline B cell subsets were collected on 145 of these. The mean count ±SD was 279mm3 ±175 (range 44-1290) . Sampling was performed on average 92±62 days prior to dosing. 136 individual pwMS had sampling performed after the first infusion (194 samples in total). In 101 pwMS, between the first and second infusion, the mean B cell counts were 15mm3 ±32.6 . Samples were performed 171±40 days after the first infusion. In 32 pwMS sampled between second and third infusions, mean cell B counts were 13.9mm3 ±29.6 . Samples were performed 353±63 days after the 2nd infusion. In the naïve subgroup (n=10 vs n=71 not naive) there was a more significant drop in B cells 7.7 vs 18.6 (p=0.038) with treatment. However they did not experience more adverse effects. Adverse effects were seen in 54/83 subjects. 21/54 had infusion related reactions. 43 reported infections including herpes (1), cellulitis (1), gastroenteritis (6), upper (18) or lower respiratory tract (7), urinary tract infections (22) or other infection (8). In those who had adverse effects there was no difference in the B cell counts at baseline. However, those who developed infections had a significant reduction in B cells (infection 6mm3 vs no adverse effects 28mm3, p=0.045). This difference persisted after the second dose (infection 5mm3 vs no adverse effects 27mm3, p=0.19). There was however no difference in the absolute lymphocyte counts (p=0.8) , CD8 or NK cells.
This data suggests that regular monitoring of B cell counts, rather than absolute lymphocyte counts, may be a method of identifying those patients at risk of adverse effects, such as infection, following ocrelizumab.