San Luigi Gonzaga Hospital
SCDO Neurologia & Centro di Riferimento Regionale Sclerosi Multipla

Author Of 5 Presentations

COVID-19 Late Breaking Abstracts

LB1234 - COVID-19 infections in NMOSD and MOGAD: a population based study (ID 2114)

Speakers
Presentation Number
LB1234
Presentation Topic
COVID-19

Abstract

Background

SARS-COV-2 pandemic poses an imminent threat to humanity and in particular in those people suffering chronic diseases. Immune-mediated disease, as NMOSD and MOGAD, could be at a higher risk of severe forms of COVID-19 both for the disease itself and for immunosuppressive treatments.

Objectives

To evaluate the prevalence and severity of COVID-19 infection in the NMOSD/MOGAD population in Italy and evaluate possibily risk factors for disease outcomes.

Methods

The MS Study Group of the Italian Neurological Society has set up a proactive programme to provide information about COVID-19 in NMOSD/MOGAD patients, using a semistructured survey.

Results

569 NMOSD/MOGAD patients from 40 Italian MS Centres have been censored for COVID-19.

68% (387/569) of the patients were treated with rituximab, 16% (91/569) with azathioprine, 4.4% (25/569) with tocilizumab, 5.4% (31/569) with other therapies and 6.2% (35/569) were untreated or without information.

8/569 patients (1.4%) were diagnosed having confirmed or highly suspected COVID-19: positive rhino-pharyngeal swabs for SARS-CoV-2 were found in 4 out of 6 tested patients.

At the time of data collection, 6 patients recovered, 1 was still hospitalised and, unfortunately, 1 died. Hospitalisation was required for 3 patients.

5/8 (68%) patients were treated with rituximab. There was no evidence of any difference of such a percentage with the one of the overall population (OR=0.78, 95%CI=0.18-3.31, p=0.74).

COVID-19 infection was classified mild in 5, severe in 2 and critical in 1. The main experienced symptoms were fever, cough, fatigue and shortness of breath. 5/8 patients experienced CNS symptoms as headache (3), dizziness (1), anosmia (1) and delirium (1).

Conclusions

1) the prevalence of COVID-19 infection appears low in NMOSD/MOGAD patients (1.9%) with a mortality rate similar to that of the general italian population (12.5% vs 14.3%);

2) no other risk factors for severe course of COVID-19 than those already known emerge;

3) the baseline use of biologics, and in particular anti-CD20 monoclonal antibodies, is not associated with a higher risk of COVID-19 infection and apparently not with worse COVID-19 outcomes

Even if preliminary, these findings suggest a cautious optimism in the care of these autoimmune conditions during the pandemic phase.

The MS Study Group: M Inglese, A Di Sapio, D Vecchio, P Cavalla, A Protti, M Radaelli, S Malagu', A Gajofatto, D Landi, G Marfia, MP Amato, A Lugaresi, C Scandellari, S Bonavita, P Perini, F Rinaldi, D Centonze, S Di Lemme, P Immovilli, U Aguglia, M Zaffaroni, S Montepietra, L Moiola, M Filippi, MT Ferro', M Salvetti, MC Buscarinu, F Granella, M Dotta, M Mirabella, M Lucchini, G De Luca, C Tortorella, C Gasperini, G Maniscalco, D Ferraro, E Cocco, R Bergamaschi, M Ulivelli, P Valentino, M Falcini, L Brambilla, G Lus, M De Riz, M Trojano, P Ragonese, A Bertolotto

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Disease Modifying Therapies – Mechanism of Action Poster Presentation

P0273 - A multicentre, real-life study on the risk of lymphopenia and infections discloses a favourable safety profile of cladribine in MS patients. (ID 1086)

Speakers
Presentation Number
P0273
Presentation Topic
Disease Modifying Therapies – Mechanism of Action

Abstract

Background

Background. Lymphopenia monitoring during treatment with disease modifying drugs for MS is relevant because of the potential increased risk of infections. Lymphopenia is an anticipated effect of cladribine (CLD) treatment, given its mechanism of action.

Objectives

Objectives. We aimed to i) characterize the absolute lymphocyte count (ALC) changes, and ii) evaluate the risk of infections in CLD-treated RRMS patients. ALCs were graded according to the Common Terminology Criteria for Adverse Events (CTCAE v5.0).

Methods

Materials and methods. In this observational multicentre study, demographic, clinical and MRI data of the patients included in the Free Of Charge CLD program were collected. ALC was also collected at baseline (before therapy initiation) and at month 3, 7, 12, 15, 19 and 24.

Results

Results. 236 patients were enrolled in 56 Italian MS Centres (71% F; mean age: 39+11.5 years; mean disease duration: 10+8.5 years). The median baseline EDSS was 3.0 (quartiles 1.5-3.5; range 0-6.5). 53 patients (22.5%) were treatment naïve, 107 (45.3%) switched to CLD from first line DMDs (for inefficacy), 76 (32.2%) switched to CLD after a second line therapy (33/76 for safety reason, 43/76 for inefficacy). Mean follow up was 12.2+5 months. At baseline, median ALC was 1615.0 cell/mm3 (quartiles, 1300.0-2200.0). At month 3, ALC was available in 190/236 and 101/190 had lymphopenia: 12 (6.3%) grade 3, 47 (24.7%) grade 2 and 42 (22.1%) grade 1. Among patients presenting grade 3 at month 3, only one had persistent ALC <500 cell/mm3 at month 7. At month 7, ALC was available in 180/236 and 77/180 had lymphopenia: 1 (0.6%) grade 4, 1 (0.6%) grade 3, 43 (23.9%) grade 2 and 32 (17.8%) grade 1. Up to date, 159/236 patients were re-treated. No retreatment was delayed because of grade 4 lymphopenia. No patient presented grade 4 lymphopenia at month 15, 6/89 (6.6%) experienced grade 3, 37/89 (40.7%) grade 2, 17/89 (18.7%) grade 1. At month 19, 1/38 (2.6%) presented grade 3 lymphopenia, 11/38 (29.0%) grade 2 and 9/38 (23.7%) grade 1. At month 24, 1/9 (11.1%) patient presented grade 3 and 1/9 (11.1%) presented grade 4 lymphopenia. During treatment course, 15 patients experienced infections (1 VZV, 3 HSV), none occurring in grade 3 or 4 lymphopenia.

Conclusions

Conclusions. In our study, the risk of grade 3 and 4 lymphopenia was lower compared to that observed in RCT. Moreover, grade 3 lymphopenia was transient in the majority of the patients. Compared to RTC, a more favourable CLD safety profile emerged in our study.

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Disease Modifying Therapies – Risk Management Poster Presentation

P0286 - Alemtuzumab following natalizumab: a multicentric Italian real-world experience (ID 993)

Speakers
Presentation Number
P0286
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

Alemtuzumab was approved by EMA in 2013 for active relapsing-remitting multiple sclerosis patients (RRMS). The ideal candidate is an active patient in early phase of disease. iIn real world alemtuzumab is also used when many treatments before have failed. Patients with long-term natalizumab exposure and anti JCV seropositivity who stop natalizumab for the risk of PML are a category of patients for whom no specific therapeutic strategy has been established.

At present, neurologists have may highly active drugs but there are no head to head studies directly comparing the efficacy of alemtuzumab with other efficacious therapies and the decision to chose the most suitable medication depends on different factors, such as the potential side effects. In patients who stop natalizumab alemtuzumab can represent a choice.

Objectives

The aim ot this observational study was to evaluate the efficacy and safety of alemtuzumab when used in patients previously treated with natalizumab.

Methods

This is a multicentric retrospective observational study.

Study population is composed by 50 RRMS patients (18 male and 32 female) with a median EDSS of 2 (range 1-7) from five Italian Multiple Sclerosis Centres who stopped natalizumab treatment after a median number of 22 infusions (range 3-114).

Five out of 50 patients were JCV seronegative and in these patients decision to stop natalizumab was due to radiological activity during natalizumab (2 patients), hypertransaminasemia (2 patients), patient request (1 patient). 45 out of patients were JCV seropositive and for these patients reason for stopping was the risk of PML.

Switch to alemtuzumab was made after a median wash out period of 2 months (range 0,7-5 months).

Patients underwent brain MRI at the end of natalizumab treatment, at 6 and 12 months after alemtuzumab infusion.

Results

Brain MRI at six months after alemtuzumab was available for 48 out of 50 patients and in 43 of them neither signs of disease activity nor new lesions were present; 3 patients showed new lesions and 1 patient had radiological activity. No patient showed clinical activity.

Brin MRI at 12 months after alemtuzumab was available in 46 out of 50 patients and in 42 out of 46 there was no sign of disease activity. In 4 patients brain MRI showed disease activity (1 pt) or new lesions (2 pts ) or both (1 pt).

Clinical relapse after alemtuzumab therapy occurred in 1 out of 50 patients; this patient underwent the third infusion of drug.

No patient developed PML.

Conclusions

Alemtuzumab started shortly after natalizumab interruption was highly efficacious in controlling disease course, as 87% of patients showed no evidence of clinical and radiological activity one year after treatment starting.

The choice of alemtuzumab use in JCV seropositive patients must take in consideration the necessity to treat a very severe disease and the safety profile of the drug to which switching.

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Observational Studies Poster Presentation

P0910 - Relapse-free and NEDA status with Cladribine in a real life population: a multicentre study (ID 1484)

Speakers
Presentation Number
P0910
Presentation Topic
Observational Studies

Abstract

Background

Trials leading to Cladribine (CLD) approval for the treatment of Multiple Sclerosis (MS) were conducted over a decade ago: there is a need of proof of CLD efficacy and safety profile in the present MS therapeutic landscape.

Objectives

To evaluate CLD efficacy and safety profile in the current MS population, and to identify early predictors of response.

Methods

Before the drug was marketed under the national healthcare system, in Italy CLD was available through a Free Of Charge (FOC) program. We asked all participating MS centres to contribute to the present study, collecting demographic, clinical and MRI data of the patients who received CLD in the FOC program.

Results

56 MS centres participated to the study, for a total of 236 patients (71% F) (mean age: 39 + 11,5 years; mean disease duration: 10 + 8,5 years). Mean Annualized Relapse Rate (ARR) in the two years before CLD was 0,7 + 0,6; median baseline EDSS was 3 (quartiles 1,5-3,5; range 0-6,5). 53 patients (22,5%) were treatment naïve, 107 (45,3%) switched to CLD from first-line DMDs (for inefficacy), 76 (32,2%) switched to CLD from a second line therapy (33/76 for safety or loss of tolerability, 43/76 for inefficacy). Mean follow up was 12,2 + 5 months. 84,7% of the patients were relapse-free at follow-up. Mean ARR at follow-up was 0,2 + 0,6. Patients taking CLD as first therapy were less likely to experience a relapse (HR 0,6; 95% CI: 0,2-0,8; p = 0,04) while a higher baseline ARR was a predictor of clinical activity (HR 2,7, 95% CI: 1,4-5,6; p = 0,004). Median EDSS at follow up was 2 (quartiles 1-3,5). EDSS was stable in 73.7%, improved of at least 1 point in 21,6% and worsened of at least 1 point in 4,7% of the patients. 157/236 patients completed one year of follow up. Of these 92 (59,7%) reached No Evidence of Disease Activity (NEDA-3); NEDA-3 was achieved more frequently by naive patients (70%) than switchers from a first (57%) or a second line (50%) (HR 2,3; 95% CI: 1,01-5,3; p = 0,04). 33/236 patients reported at least one adverse event (AE), most frequently infections (15 cases); other AEs included gastrointestinal side effects, cutaneous rash, aphthous stomatitis and headache. Two severe AEs were reported (one pneumonia, one melanoma).

Conclusions

Even with the limitations of a retrospective study, our data confirm CLD safety and efficacy profile. Consistently with previous studies on patients with a first demyelinating event, CLD efficacy is maximized when used early in the course of MS.

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Observational Studies Poster Presentation

P0913 - Risks associated with wash-out duration when switching from fingolimod to cell-depleting agents (ID 1317)

Abstract

Background

A wash-out duration lasting >1–2 months between the majority of sequential disease-modifying therapies (DMTs) is associated with an increased risk of disease reactivation in Multiple Sclerosis (MS) patients.

Fingolimod (FTY) induces sequestration of lymphocytes in secondary lymphoid organs and the average lymphocyte recovery following discontinuation takes 1-2 months. It has been hypothesized that the therapeutic effects of subsequent cell-depleting agents may be compromised if lymphocyte recovery is still incomplete and that shorter wash-out periods do not affect the disease reactivation risk.

Objectives

To assess the risk of relapses following FTY discontinuation and the initiation of a B/T cell-depleting agent initiation in relation to the duration of wash-out between the drugs using data from the Italian MS Registry.

Methods

Patients who initiated alemtuzumab, rituximab, ocrelizumab or cladribine within six months of FTY discontinuation, and with a follow-up of at least six months, or until a relapse occurred, were included in the study. The risk of relapses was assessed in relation to different wash-out durations (<6, 6-11, 12-17 and >/=18 weeks) using a Poisson regression analysis (and reported as incidence rate ratio - IRR) and a Cox proportional hazards model including age, disease duration, relapses during FTY treatment, EDSS and reason for FTY discontinuation as covariates.

Results

Inclusion criteria were met by 329 patients (226F, 103M; mean age 41±10 years). Following a median wash-out period of 11 weeks [IQR: 6-16], 175 patients started alemtuzumab, 69 rituximab, 68 ocrelizumab and 17 cladribine. Ninety patients relapsed during the wash-out period and 72 during the subsequent cell-depleting therapy. During the cell-depleting treatment, IRR for a relapse was significantly greater in patients with a washout-period of 12-17 (IRR (95%CI): 2.4 (1,1-5,5); p=0.037) and >/=18 weeks (6.0 (2.8-12.7); p<0.001) compared to the reference period (<6 weeks).

The multivariable Cox analysis showed that the time to a relapse was significantly influenced by the occurrence of relapses during FTY treatment (HR (95%CI): 1.4 (1.2-1.7); p<0.001). Moreover, wash-out durations of 6-11, 12-17 and >/=18 weeks were associated with a higher risk of a relapse in comparison to wash-out durations shorter than 6 weeks (3.8 (1.1-13.2); p=0.037; 6.0 (1.7-21.9); p=0.006; 16.3 (4.8-56.3); p<0.001, respectively).

Conclusions

The risk of relapses during a cell-depleting therapy following a sequestering agent, namely FTY, increases progressively with the duration of wash-out, underlining the need of a short wash-out period also in this type of treatment sequence.

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Presenter Of 1 Presentation

COVID-19 Late Breaking Abstracts

LB1234 - COVID-19 infections in NMOSD and MOGAD: a population based study (ID 2114)

Speakers
Presentation Number
LB1234
Presentation Topic
COVID-19

Abstract

Background

SARS-COV-2 pandemic poses an imminent threat to humanity and in particular in those people suffering chronic diseases. Immune-mediated disease, as NMOSD and MOGAD, could be at a higher risk of severe forms of COVID-19 both for the disease itself and for immunosuppressive treatments.

Objectives

To evaluate the prevalence and severity of COVID-19 infection in the NMOSD/MOGAD population in Italy and evaluate possibily risk factors for disease outcomes.

Methods

The MS Study Group of the Italian Neurological Society has set up a proactive programme to provide information about COVID-19 in NMOSD/MOGAD patients, using a semistructured survey.

Results

569 NMOSD/MOGAD patients from 40 Italian MS Centres have been censored for COVID-19.

68% (387/569) of the patients were treated with rituximab, 16% (91/569) with azathioprine, 4.4% (25/569) with tocilizumab, 5.4% (31/569) with other therapies and 6.2% (35/569) were untreated or without information.

8/569 patients (1.4%) were diagnosed having confirmed or highly suspected COVID-19: positive rhino-pharyngeal swabs for SARS-CoV-2 were found in 4 out of 6 tested patients.

At the time of data collection, 6 patients recovered, 1 was still hospitalised and, unfortunately, 1 died. Hospitalisation was required for 3 patients.

5/8 (68%) patients were treated with rituximab. There was no evidence of any difference of such a percentage with the one of the overall population (OR=0.78, 95%CI=0.18-3.31, p=0.74).

COVID-19 infection was classified mild in 5, severe in 2 and critical in 1. The main experienced symptoms were fever, cough, fatigue and shortness of breath. 5/8 patients experienced CNS symptoms as headache (3), dizziness (1), anosmia (1) and delirium (1).

Conclusions

1) the prevalence of COVID-19 infection appears low in NMOSD/MOGAD patients (1.9%) with a mortality rate similar to that of the general italian population (12.5% vs 14.3%);

2) no other risk factors for severe course of COVID-19 than those already known emerge;

3) the baseline use of biologics, and in particular anti-CD20 monoclonal antibodies, is not associated with a higher risk of COVID-19 infection and apparently not with worse COVID-19 outcomes

Even if preliminary, these findings suggest a cautious optimism in the care of these autoimmune conditions during the pandemic phase.

The MS Study Group: M Inglese, A Di Sapio, D Vecchio, P Cavalla, A Protti, M Radaelli, S Malagu', A Gajofatto, D Landi, G Marfia, MP Amato, A Lugaresi, C Scandellari, S Bonavita, P Perini, F Rinaldi, D Centonze, S Di Lemme, P Immovilli, U Aguglia, M Zaffaroni, S Montepietra, L Moiola, M Filippi, MT Ferro', M Salvetti, MC Buscarinu, F Granella, M Dotta, M Mirabella, M Lucchini, G De Luca, C Tortorella, C Gasperini, G Maniscalco, D Ferraro, E Cocco, R Bergamaschi, M Ulivelli, P Valentino, M Falcini, L Brambilla, G Lus, M De Riz, M Trojano, P Ragonese, A Bertolotto

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