Real-world comparison of anti-CD20 therapies: efficacy, infections, and immune profiles in a German cohort

Abstract

Background: The use of anti-CD20 drugs has become a widespread therapeutic approach in systemic and central nervous system (CNS) neuroinflammation. Apart from the desired B-cell depletion, relevant dynamics of the humoral and cellular immune response occur. Despite the extensive utilization of these drugs, direct comparative analyses of various B-cell-depleting agents remain scarce.

Methods: A total of 262 patients with neuroimmunological diseases treated with ocrelizumab, ofatumumab, or rituximab were observed over a median period of 36 months. Relapses, infection rates, and the concentration of immunoglobulins were monitored quarterly. In addition, changes in cellular immunity (differential blood count, natural killer cells, CD19⁺, CD3⁺, CD4⁺, and CD8⁺ cells) along with polyclonal T-cell function (measured by reactivity) were analyzed using multidimensional flow cytometry.

Results: Annual relapse rates in both the ocrelizumab and ofatumumab groups were low: 0.11 [95 % confidence interval (CI), 0.06 - 0.15] and 0.08 (95% CI, 0.05 - 0.16), respectively. Infections occurred significantly less frequently with ofatumumab (p < 0.001). Hypogammaglobulinemia was observed more frequently and earlier in rituximab patients (p < 0.001). Ocrelizumab treatment was associated with a reduction in the proportion of total lymphocytes and an increase in the proportion of CD3⁺ T cells, while ofatumumab was linked to a rise in the CD4/CD8 ratio. Anti-CD20 antibodies did not influence T-cell reactivity after polyclonal stimulation.

Conclusions: B-cell depletion is effective in neuroimmunological diseases irrespective of which CD20 antibody was used. However, differences in infection rates and the occurrence of hypogammaglobulinemia were observed. Together with new insights into differences in the influence of CD20 antibodies on lymphocyte subpopulations, these findings may inform future individualized treatment strategies.

Keywords: B-cell depletion; T-cell function; cellular immune status; multiple sclerosis; neuroimmunological diseases; ocrelizumab; ofatumumab; rituximab.