Short-term evaluation of alemtuzumab to ocrelizumab switch in MS patients with disease activity after alemtuzumab: An italian multicentric study

ABSTRACT

Background: the management of MS patients (pts) who show disease activity after 2 alemtuzumab (ALM) courses represents an unsolved issue. No real-life data about the switch to ocrelizumab (OCR) have been reported yet. Objectives: To describe efficacy and safety outcome of OCR patients switching from ALM due to persistence of disease activity after ALM Methods: MS pts who switched from ALM to OCR from March 2019 to March 2020 were retro- and prospectively recruited from different Italian MS Centers. Clinical, immunological and neuroradiological data about ALM treatment period, ALM-OCR interval and OCR treatment period were collected. Results: we recruited 23 MS pts [mean age 35.7(SD±6.8);female, 40.1%;Relapsing Remitting, (RR) 75.8%, active Secondary progressive, (aSP) 24.2%;mean time interval (days) from II ALM course 87.4(SD±108);cumulative number of relapses 21;mean number of new T2 and Gd+ lesions 4.1(SD±4.5) and 1.6(SD±3.1);median EDSS3(range 1-7)]. The mean follow-up (FU) from OCR start was 7.9±7.4 months. Efficacy 4 (17.4%) pts had a relapse after OCR start (1 pt relapsed between the first and the second OCR infusion and 3 pts after 3, 11 and 15 months from OCR start respectively), with complete recovery after steroid treatment. 4 (17.4%) pts showed radiological activity with no clinical correlates at 3 months (n=2), 4 months (n=1) and 9 months (n=1). EDSS was stable except for 1 aSP patient who showed 1-year disability progression. Safety I) Infusion Associated Reactions (IARs) occurrence was significantly lower with respect to alemtuzumab courses (p<0.05);(ii) infections mild upper airways (n=1), urinary infections (n=1), appendicectomy (n=1) and fever due to probable Sars-Cov2 infection (n=1). For 12 pts, data about immunophenotype were available. Of them, no pts showed T CD4+ cell count decrease <200 cell/mm3 at 3, 6-months and 1-year FU;complete B CD19+ cell depletion (<5 cell/mm3) was confirmed at 3, 6-months and 1-year FU. 10 (43.4%) pts developed hypogammaglobulinemia without developing associated infectious events. C) Autoimmunity no alemtuzumab-related new complications occurred. Conclusions: short-term FU seems to suggest that the switch to OCR in MS patients who showed disease activity after 2 ALM courses is characterized by a good safety and efficacy profile, although clinical and neuroradiological activity can be detected both in an early and in a later phase of treatment. Longer followup is warranted and recruitment is still ongoing.