Background

ocrelizumab (OCR) treatment in pivotal trials of patients (pts) with relapsing-remitting multiple sclerosis (RRMS) was associated with high clinical efficacy and safety. However, real word data on efficacy and safety are still scarce

Objectives

To provide first experience on patients with RRMS treated with OCR in a single center real-world setting (MS Center of University of Genoa)

Methods

We collected safety and efficacy data from pts with RRMS treated with OCR. The probability of disability worsening-free survival, relapse-free survival, MRI-activity free-survival and NEDA-3 status was calculated with the Kaplan-Meier estimator and Cox proportional hazards regression analysis.

Results

96 RRMS pts [60 females (62.5%), mean (SD) age 37.3 (10.2) years] with a mean disease duration (DD) of 9.6 (9.3) years, a median (IQR) baseline EDSS of 2.5 (2-4) and a mean ARR of 0.79 (0.73). Median (IQR) number of previous DMTs was 1 (0-2). The mean time from previous DMT discontinuation and OCR start of 209 (661) days. Reasons for previous DMTs discontinuation were (i) lack of efficacy for 45 (67%), (ii) occurrence of adverse events for 7 (10%) and (iii) high JCV titer during natalizumab treatment for 5 (7.5%) pts. 28 pts (29.5%) had not received any DMT prior to OCR. Naïve pts had significantly shorter disease duration (2.6 vs 12.5 years; p<0.0001), had higher ARR (1.1 vs 0.7; p=0.002) and more frequently exhibited inflammatory activity on baseline MRI scan (96.3% vs 74.6%; p=0.019). Mean follow-up (FU) was 1.4 (1.2) years.

At 1-year FU, MRI-inflammatory activity free survival was 75.9%, relapse free survival was 95.9%, progression free survival was 98.7%. 2-years NEDA-3 status was achieved in 73.6% of pts. At multivariate analyses, adjusting for DD, ARR and baseline MRI activity, 2-years NEDA-3 status was significantly higher in naïve compared with treated pts [90.7% versus 60.8% at the end of the observation period; HR (CI 95% ) 0.14 (0.03-0.65); p=0.012]. We recorded 55 adverse events in 39 pts (4 lower respiratory tract infections; 18 upper respiratory tract infections; 7 herpes simplex-1 reactivation; 1 shingles; 8 upper urinary tract infections; 2 breast cancers). No serious infusion-associated reactions were reported

Conclusions

OCR treatment allows complete disease control in a high proportion of real-world RRMS pts, with a manageable safety profile. Although ocrelizumab can control disease activity after failure of highly efficacy DMTs, its efficacy seems to be higher in naïve patients

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 follow-up is warranted and recruitment is still ongoing.

Background

Ocrelizumab (OCR) treatment in pivotal trials of patients (pts) with progressive multiple sclerosis (PMS) has demonstrated to slow disability worsening, with a good safety profile. However, real-word data on efficacy and adverse events (AE) are still scarce.

Objectives

To provide first experience data regarding efficacy and safety of OCR use in PMS pts treated within a real-world setting.

Methods

We collected safety and efficacy data from all PMS pts treated with OCR at the MS Center of the University of Genoa. The probability of disability-, relapse- and MRI activity-free survival and NEDA-3 status was calculated with Kaplan-Meier estimator and Cox proportional hazards regression analysis. AE were recorded throughout the follow-up (FU).

Results

We recorded data from 59 PMS pts [42 (71%) with primary-progressive (PP) MS and 17 (29%) with secondary progressive (SP) MS, 24 females (41), mean (SD) age 49.8 (8.2) years] with a mean disease duration (DD) of 12.1 (10.1) years, a median (IQR) baseline EDSS of 5.5 (3.5-6.0) and median number of previous DMTs 1 (0-2). SPMS patients had longer DD (20.8vs8.6; p=0.004) and had mean ARR of 0.24 (0.4). 21 (36%) pts had not received any DMT prior to OCR. Mean FU was 2.0 (1.1) years. 14 (24%) patients had an active MRI brain scan at baseline. At 1-year FU, MRI-inflammatory-activity-free survival was 87.3% (CI95%: 76.9-97.7%), relapse-free survival was 100% and progression-free survival was 82.7% (72.3-93.1%). NEDA-3 status was achieved in 72.3% (59.0-85.5%) of pts. No differences were noted between patients with PP and SPMS. At multivariate analyses, no baseline characteristic was found be predictive of a higher probability of progression-free survival, MRI-activity-free survival and NEDA-3 status. We recorded 69 AE in 36 pts (32 upper respiratory tract infections; 6 herpes simplex-1 reactivation; 7 lower urinary tract infections; 1 acute myeloid leukemia following myelodysplastic syndrome; 1 appendicitis treated with surgical procedure). No serious infusion-associated reactions were reported.

Conclusions

We report short-medium term efficacy data in a real-world population of progressive patients treated with OCR, including a relatively high proportion of patients without MRI activity at baseline assessment. Our data suggest that OCR should be considered as treatment option in both patients with PPMS and SPMS.

Background

Management of multiple sclerosis (MS) patients who discontinue fingolimod (FTY) is not established yet and breakthrough disease activity has been reported following fingolimod withdrawal. However, data regarding this phenomenon and its possible impact in the long-term are still sparse.

Objectives

To explore frequency of disease reactivation after FTY cessation in a single-center cohort and clinical/radiological characteristics of patients (pts) discontinuing FTY during (I) the wash-out period and (II) the first 12-months following a new treatment onset.

Methods

Data regarding relapses, Expanded Disability Status Scale (EDSS), MRI activity (new T2 and/or Gd-enhancing lesion) and lymphocyte count before and during FTY treatment, the wash-out period and the first 12-moths of a new treatment were retrospectively collected. Pts were grouped according to (I) discontinuation reason (inefficacy/adverse events/other reasons) and (II) disease activity during wash-out (no disease activity/at least one relapse or MRI activity/rebound). Differences in clinical/radiological characteristics or time to NEDA3-failure between groups were assessed with ANOVA, Chi-square and Kaplan-Meier estimator as appropriate.

Results

We included 71 pts [females:70%; mean age and disease duration at FTY start:37.6±8.4 and 11±7.6 years; median EDSS:3 (0-7); mean treatment duration:2.3 year]. 70% discontinued for inefficacy, 22% for adverse events, 8% for other reasons (pregnancy/pts’s choice). During the wash-out 69% of pts remained stable, 21.2% had clinical/radiological activity, 9.8% had a rebound (mean wash-out period: 2.3, 8.2, 4.1 months, respectively; p=0.03). Age was lower in rebound vs stable pts (28.5±4.9vs39.4±8.3; p=0.006). Discontinuation for inefficacy was observed in 70% of stable, 93% of clinically/radiologically active and 42% of pts with a rebound during wash-out (p<0.0001). No differences in time to NEDA3-failure during the first 12-months following a new treatment start were observed according to discontinuation reason or disease activity during wash-out (Log-Rank test: p=0.67 and p=0.23, respectively). Disease duration, EDSS, lymphocytes’ count at FTY stop and lymphocytes’ increase during wash-out did not differ according to disease activity during wash-out or response to following treatment.

Conclusions

Younger pts were more likely to have a rebound, while more frequent discontinuation for inefficacy and longer wash-out period were observed in pts with clinical/radiological activity during wash-out. Time to NEDA3-failure within the 12-months following a new treatment onset was not influenced by discontinuation reason or disease activity during wash-out

Background

Theory of Mind (ToM, i.e the ability to decode emotional states) is a cognitive function that plays a key role in social functioning. While ToM deficits have been found to be frequent in subjects with MS, ToM is not routinely assessed in formal neuropsychological assessments in this population. The lack of inclusion of ToM assessment in routine neuropsychological evaluation of MS patients, stems from different causes including a partial characterization of the association between general cognition and ToM in the different phases of the disease.

Objectives

To evaluate the interaction between clinical course (relapsing remitting MS (RRMS) vs progressive MS (PMS)), ToM deficits and general cognition. More in detail we aim to assess if the role played by general cognitive functioning on ToM is different in PMS rather than in RRMS

Methods

120 MS patients (age: 44.9±11.6 years, median EDSS 2.5 range 1-6; 75 subjects with RRMS and 45 with PMS) were assessed with the Symbol Digit Modalities Test (SDMT) to evaluate general cognition and the Reading the Mind in the Eyes Test (RMET) to evaluate ToM. The RMET, developed by Baron-Cohen and colleagues in 2001 is a standardized test that consists of 36 black and white picture of the eye region; the subject has to recognize the emotional state represented in the picture and choose one among four given words that depict an emotion.

Results

Comparing RRMS and PMS patients, there was a significant difference in SDMT (55.3±12.0 vs 40.2±11.0, p=0.001) and in total RMET (27.0±4.0 vs 22.9±3.0 p=0.001) scores. There was a significant correlation between SDMT and ToM in the whole sample (p<0.001, r=0.45) and in the RRMS group (p=0.001, r=0.48, but not in PMS (p=0.83) group.

Conclusions

The association between SDMT and RMET is modulated by clinical course in MS. This observation suggests that a bigger role is played by general cognition on RMET in RRMS rather than in PMS possibly due to the presence of more diffuse damage in PMS. Our data suggest that these two metrics change differently over the disease course and thus provide complementary information in the study of cognitive deficits in MS.