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

Objective: To evaluate efficacy and Safety of multiple sclerosis (MS) patients (pts) who switched to ocrelizumab (OCR) due to persistence of disease activity after two courses of alemtuzumab (ALM) Background: The management of MS pts who show disease activity after 2 ALM courses represents an unsolved issue Design/Methods: MS patients who switched from ALM to OCR from March 2019 to March 2020 were retro-A nd 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: 23 MS pts [mean age: 35.7(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(108);cumulative number of relapses: 21;mean number of new T2 and Gd+ lesions: 4.1(4.5) and 1.6(3.1);median EDSS:3(range 1-7)]. The mean follow-up (FU) from OCR start: 7.9±7.4 months. 4 (17.4%) pts had a relapse after OCR start (1 during the interval between first and the second OCR infusion and 3 pts after 3, 11 and 15 months from OCR start. 4 (17.4%) pts showed only radiological activity at 3 (n=2), 4 (n=1) and 9 months (n=1). Infusion Associated Reactions occurrence was lower than ALM courses (p<0.05) ;mild upper airways (n=1), urinary infections (n=1), appendicectomy (n=1) and fever due to probable Sars-Cov2 infection (n=1). No pts showed T CD4+ cell count <200 cell/mm3 at 3, 6-months and 1-year FU;B CD19+ cell depletion (<5 cell/mm3) was confirmed at 3, 6-months and 1-year FU with the exception of 1 pt (B CD19+ count 12 cells/mm3 at 6 month FU (n=12 pts)). 10 (43.4%) pts developed hypogammaglobulinemia without infectious events. No ALM-related new complications occurred. Conclusions: Short-term FU suggests that the switch to OCR in MS after 2 ALM courses is characterized by a good safety and efficacy profile.

Personalizing ocrelizumab treatment in Multiple Sclerosis: What can we learn from Sars-Cov2 pandemic?

During SARS-CoV-2 pandemic, we adopted a personalized delayed protocol for ocrelizumab infusions in Relapsing Remitting Multiple Sclerosis (RRMS) patients according to the national recommendations. Out of the 83 RRMS patients whose infusion was scheduled between March and December 2020, 56 patients experienced a delay in treatment based on MS severity and SARS-CoV2 infection risk profile. In most cases, the immunophenotype was performed monthly to guide re-infusions. Specifically, B CD19 + cells repopulation rate was monitored. Mean infusion delay was 103,1 [SD 40,6] days, and none of the patients presented relapses or active disease at MRI at the end of the observation period. Treatment naïve status and the interval between immunophenotyping and the last ocrelizumab infusion were predictors of earlier B CD19 + cells repopulation. Two patients contracted SARS-CoV2 with complete recovery. Definitive data about Sars-Cov2 vaccine efficacy in patients treated with ocrelizumab are still lacking. Our findings suggest that a personalized treatment with a delayed infusion schedule does not compromise ocrelizumab short-term efficacy and may help to lengthen the therapeutic window for an effective response to SARS-CoV2 vaccine.

Treatment with ocrelizumab during SARS-CoV2 pandemic: Efficacy and safety outcomes

Background: Sars-Cov2 pandemic led neurologists to modify the therapeutic approach in Multiple Sclerosis (MS) care setting, especially with regard to immunodepleting treatments. Objectives: to describe management and outcome of MS patients (pts) treated with ocrelizumab (OCR) during Sars-Cov2 pandemic in the MS Center of University of Genoa. Methods: we collected data about pts scheduled to undergo OCR infusion from 1st March to 30th June 2020. Pts that previously underwent the first OCR infusion completed the induction cycle. No further OCR cycles during March and April 2020 were performed. Starting from May, we adopted an infusion scheme based on B-cell repopulation, differently applied for Relapsing Remitting (RR) and Progressive (P) pts. RRMS pts performed immunophenotype (IF) and received OCR infusion when B CD19+ cell count overcame the cut-off of 1%. Conversely, for PMS pts OCR infusions were delayed for 3 months. Then, PMS pts underwent OCR infusion based on B CD19+ cell monitoring. For pts with evidence of B CD19+ cells repopulation brain 3T MRI was planned before OCR re-infusion. Results: 77 MS pts were included [45 (58%) RRMS, 32 (41%) PMS;mean age 44.7 (SD: 11.1) years, mean disease duration 21.7 (22.3) years, mean number of previous DMT before OCR: 1.6 (1.6), mean number of previous OCR infusions 3.9 (SD 2.3). 11 (13.1%, 9 RR, 2 PP) of the 49 pts that performed a first IF presented B CD19+ cell repopulation and received OCR re-infusion, with a mean delay from scheduled infusion of 70 (48.9) days. The mean number of previous OCR infusions was 3.0 (1.2) and 3.1 (1.6) for pts with and without evidence of B-cell repopulation respectively. No effect of previous OCR infusions number on the probability to develop B CD19+ cell repopulation at the first IF was detected by ANCOVA analysis, correcting for the delay between the date of scheduled infusion and the date in which the first IF has been performed. Considering the global cohort, 1 pt presented a dubious sensory relapse with no evidence of radiological activity. None of the pts who performed brain MRI before OCR re-infusion showed new T2 or Gd+ enhancing lesions. 3 pts were infected by Sars- Cov2;2 of them needed hospitalization but recovered completely. Conclusions: the management of patients treated with OCR during Sars-Cov2 pandemic with a personalized infusion protocol based on B CD19+ cells repopulation was associated with good results in terms of efficacy and safety outcome.

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

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 EDSS:3(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.