Previous disease-modifying treatments influence T lymphocyte kinetics in people with multiple sclerosis switching to ocrelizumab

Background: Recently, concern has been raised about the influence of the previous disease-modifying treatments (DMTs) on the clinical efficacy of ocrelizumab (OCR). We aimed to evaluate whether the previous DMT affects the lymphocyte subset kinetics in people with Multiple Sclerosis (MS) switching to OCR.Methods: This is a multicenter, retrospective, real-world study on consecutive MS patients who started or switched to OCR. We grouped them by prior DMT in: (i) naive-to-treatment (NTT), (ii) switching from fingolimod (SF) and (iii) switching from natalizumab (SN). Differences in absolute lymphocyte count and lymphocyte subset count changes, considering the period from baseline to 6 months, over all the three groups were assessed with an inverse-probability-weighted regression adjustment model.Results: Mean T CD4+ cell count reduction from baseline to the six-month follow-up was more pronounced in the SN group compared to the NTT (p = 0,026). Further, patients in the SF group experienced a less pronounced CD4 T cell number decrease than both NTT and SN groups (p = 0,04 and p < 0,001, respectively). Patients in the SF group experienced an increase in CD8 T cell absolute number, whereas those in the NTT and SN groups expe-rienced a significant decrease (p = 0,015 andp < 0,001, respectively). Patients experiencing early inflammatory activity showed a lower CD8+ cell count at baseline than stable patients (p = 0,02).Conclusions: Previous DMTs influence the lymphocyte kinetics in people with MS switching to OCR. Reassessment of these findings over a larger population may help optimize the switch.