Predictors of Ocrelizumab Effectiveness in Patients with Multiple Sclerosis

Abstract

Data regarding effectiveness and safety of ocrelizumab in the post-marking setting are lacking. The aim of our study was to provide effectiveness and safety data of ocrelizumab treatment in patients with relapsing-remitting (RR-) and progressive multiple sclerosis (PMS) and to evaluate clinical and immunological predictors of early treatment response. In this single-center prospective observational study, we investigated effectiveness outcomes (time-to-confirmed disability worsening, time-to-first relapse, time-to-first evidence of MRI activity and time-to-first evidence of disease activity), clinical and immunological predictors of early treatment response, and incidence of adverse events (AEs). One hundred and fifty-three subjects were included (93 RRMS; 84 females). Median follow-up was 1.9 (1.3-2.7). At 2-year follow-up (FU), disability worsening-free survival were 90.5%, 64.7%, and 68.8% for RRMS, primary-progressive MS (PPMS), and secondary-progressive MS (SPMS) patients, respectively. At 2-year FU, 67.1%, 72.7%, and 81.3% of patients with RRMS, PPMS, and SPMS were free of MRI activity, with NEDA-3 percentages of 62.1%, 54.6%, and 55.1%, respectively. Lower baseline EDSS was independently associated with a reduced risk of disability worsening (HR(95%CI) = 1.45(1.05-2.00), p = 0.024) and previous treatment exposure was independently associated with increased probability of radiological activity (HR = 2.53(1.05-6.10), p = 0.039). At 6-month FU, CD8 + cell decrease was less pronounced in patients with inflammatory activity (p = 0.022). Six patients (3.9%) discontinued ocrelizumab due to severe AEs. Our findings suggest that ocrelizumab is an effective treatment in real-world patients with RRMS and PMS, with a manageable safety profile. Better outcomes were observed in treatment-naïve patients and in patients with a low baseline disability level. Depletion of CD8 + cells could underlie early therapeutic effects of ocrelizumab.

Keywords: Advanced multiple sclerosis; CD8; Highly active multiple sclerosis; Multiple sclerosis; Ocrelizumab.

Fig. 1

NEDA-3 status and individual components during ocrelizumab therapy in relapsing–remitting and progressive MS. Specifically, panel (A) shows the percentages of RRMS and PMS patients free of disability worsening throughout follow-up; panel (B) shows occurrence of relapses in RRMS and PMS throughout follow-up; panel (C) shows RRMS and PMS patients free of MRI activity throughout follow-up; panel (D) NEDA-3 percentages in RRMS and PMS patients throughout follow-up; panel (E) shows RRMS and PMS patients free of MRI activity throughout follow-up after a 100-day re-baseline of MRI activity; panel (F) shows NEDA-3 percentages in RRMS and PMS patients throughout follow-up after a 100-day re-baseline of MRI activity; panel (G) shows percentages of subjects free of disability worsening throughout follow-up in sub-groups of patients with baseline EDSS<4 and those with baseline EDSS ≥ 4 at ocrelizumab start; panel (H) shows NEDA-3 percentages in treatment-naive and previously treated patients throughout follow-up. RRMS, relapsing–remitting multiple sclerosis; PMS, progressive multiple sclerosis; EDSS, expanded disability status scale; NEDA-3, no evidence of disease activity