Real World Data of Laboratory Changes and Immunophenotyping in Patients with Multiple Sclerosis Treated with Ofatumumab—Single Center Experience

<b>Background/Objectives</b>: Ofatumumab is a fully human anti-CD20 monoclonal antibody approved for the treatment of relapsing forms of multiple sclerosis (MS). While its efficacy and safety have been demonstrated in clinical trials, real-world data focusing on laboratory changes and detailed immunophenotyping during treatment remain limited. The objective of this study was to assess routine laboratory parameters and immunophenotyping profiles in ofatumumab-treated patients in a real-world setting. <b>Methods</b>: We conducted a retrospective, single-center real-world study including 59 patients with relapsing-remitting MS treated with ofatumumab. Routine laboratory parameters were analyzed at the baseline and 6-12 months after treatment initiation. Immunophenotyping by flow cytometry was available for a subset of 29 patients. Infections were assessed during a follow-up period of at least six months. Paired comparisons were performed using the Wilcoxon signed-rank test. <b>Results</b>: Ofatumumab induced a profound and sustained depletion of CD19+ B cells (<i>p</i> < 0.001). Total T cells, CD4+ and CD8+ T-cell counts, the CD4/CD8 ratio, and natural killer (NK) cells remained largely stable over time. NK cells and helper T cells showed a numerical increase without statistical significance. IgM levels and relative lymphocyte percentages showed a statistically significant decrease compared with baseline (<i>p</i> = 0.047 and <i>p</i> = 0.016, respectively), while remaining within reference ranges. Other routine laboratory parameters remained stable. Reported infections were infrequent and predominantly mild. <b>Conclusions</b>: In this real-world cohort, ofatumumab demonstrated a favorable immunological and laboratory profile consistent with its known mechanism of action. These findings suggest that routine laboratory monitoring is sufficient for most patients, while immunophenotyping may be reserved for selected clinical scenarios. Further prospective studies integrating clinical and radiological outcomes are needed to better define the clinical relevance of these immunological findings.