Background: Monoclonal antibodies targeting CD20-expressing B cells
constitute effective therapies for people with multiple sclerosis (pwMS) and can
be administered intravenously (i.v.) or subcutaneously (s.c.). However, little is
known about the differences in immunomodulatory effects of distinct B-cell
depletion therapies.
Methods: We performed detailed characterizations of the immune cell
composition in blood samples of pwMS treated with either i.v. [ocrelizumab
(Ocre); n = 25] or s.c. [ofatumumab (Ofa); n = 25 or Ocre n = 25] administered
anti-CD20 therapy compared to healthy controls (HC, n = 20). In addition, blood
samples from n = 25 pwMS who switched their anti-CD20 therapy from i.v. Ocre
to s.c. Ofa injection were analyzed before therapy change and after 4 and 8
weeks. We performed flow cytometry analysis of whole blood samples and
purified peripheral blood mononuclear cells for intracellular cytokine staining.
Results: Both anti-CD20 mAbs resulted in a depletion of CD19+ B cells [median
(IQR) HC: 16.5 (10.1–22.2), Ocre i.v.: 0.4 (0.1–0.9), Ocre s.c.: 0.8 (0.4–1.2), Ofa s.c.:
1.7 (0.8–2.2)] and CD20+ T cells [median (IQR) HC: 9.1 (6.6–16), Ocre i.v.: 0.6 (0.1–
1), Ocre s.c.: 0.3 (0.2–0.5), Ofa s.c.: 0.1 (0.1–0.4)] in peripheral blood. More indepth
characterization of the patients’ remaining B cells indicated higher
percentages of memory B cells in Ocre and Ofa s.c. compared to Ocre i.v.
treated pwMS [median (IQR) Ocre i.v.: 6.6 (0–13), Ocre s.c.: 18.4 (4–26.8), Ofa s.c.:
26.4 (21.1–30)]. In pwMS who switched from i.v. Ocre to s.c. Ofa therapy, the
percentage of memory B cells increased over time [median (IQR) baseline: 14.6
(6.4–20.8), 4 weeks after switch: 12.1 (6–23.4), 8 weeks after switch: 22.8 (16.7–
29.5)]. I.v. Ocre treatment led to significantly lower serum IgG levels in pwMS
compared to HC.

Discussion: Our data add to the knowledge on distinct antibody-specific properties
and differential effects of s.c. versus i.v. administered B-cell depletion in pwMS. We
identified a higher percentage ofmemory B cells in s.c. Ocre and Ofa B cell-depleted
pwMS and pwMS who switched their anti-CD20 therapy from i.v. Ocre to s.c. Ofa
injection. Further analysis will be needed to investigate how these observations link to safety and efficacy profiles of the different anti-CD20 therapies.