IRCCS Foundation Neurological Institute Carlo Besta
MS Center, Neuroimmunology and Neuromuscular Diseases Unit

Author Of 2 Presentations

Clinical Outcome Measures Poster Presentation

P0150 - REWORD-MS: REal WOrld study to assess the Response to Dimethyl fumarate in patients with Multiple Sclerosis (ID 1813)

Speakers
Presentation Number
P0150
Presentation Topic
Clinical Outcome Measures

Abstract

Background

The response of relapsing-remitting Multiple Sclerosis patients (RRMSp) to disease-modifying drugs (DMDs) is heterogeneous. Tools able to predict response at the beginning of therapy are not available, but early treatment optimization is crucial to prevent disability accumulation. Scoring systems based on combination of relapse rate and new or enlarged T2 lesions (NT2) during the first year of treatment, as the MAGNIMS (Magnetic Resonance Imaging in MS) score, have been validated in RRMSp treated with interferon, to predict the individual response over time. Dimethyl fumarate (DMF) is nowadays the leading treatment prescribed among first line DMDs.

Objectives

The aim of the study is to evaluate the validity of the MAGNIMS score in predicting therapeutic failure in RRMSp treated with DMF.

Methods

Data about clinical relapses and NT2 were collected from 195 RRMSp treated with DMF for at least 12 months and with ≥ 24 months of follow-up. The MAGNIMS score was applied at month 12. Therapeutic failure was defined as EDSS (Expanded Disability Status Scale) worsening or change of therapy for inefficacy and loss of NEDA-3 status (No Evidence of Disease Activity: no relapse, no EDSS worsening, no NT2). The association between score and risk of treatment failure was evaluated by Cox proportional hazard model.

Results

At month 12, 175/195 (89.7%) patients had score=0 (no clinical relapse and <3 NT2) and 20/195 (10.3%) had score≥1 (≥ 1 clinical relapse and/or ≥3 NT2). Patients with score≥1 had a four times greater risk of EDSS worsening or change of therapy compared with patients with score=0 (HR 3.89, 95% CI 1.80-8.43; p=0.001). Similarly, the risk of losing NEDA-3 status was two times greater in patients scored ≥1 (HR 2.19, 95% CI 1.07-4.48; p=0.031). Considering RRMSp treated with DMF as first therapy (naïve, 91), patients with score≥1 had a six times greater risk of EDSS worsening or change of therapy (HR 5.86, 95% CI 2.03-16.92; p=0.001) and a two and a half times greater risk of losing NEDA-3 (HR 2.48, 95% CI 1.01 – 6.11; p=0.048).

Conclusions

Our data show that the MAGNIMS score is a reliable tool to predict response to DMF in a real world setting, even in naïve patients. Early identification of non-responders is crucial to identify candidates for a therapeutic shift to prevent disease progression. Due to the complexity of MS, future studies are needed to assess whether the addiction of other biomarkers (i.e. neurofilaments and brain atrophy) will improve the predictive power of a clinical-radiological score.

Collapse
Disease Modifying Therapies – Risk Management Poster Presentation

P0306 - Cardiovascular monitoring during alemtuzumab infusion in Multiple Sclerosis patients (ID 1880)

Speakers
Presentation Number
P0306
Presentation Topic
Disease Modifying Therapies – Risk Management

Abstract

Background

Alemtuzumab (AL) is a monoclonal antibody approved for Relapsing Remitting Multiple Sclerosis (RRMS). Infusion adverse events (AEs) are common during AL administration. AL administration protocol was revised in 2019 by regulatory agencies due to serious cardiovascular (CV) AEs. The new recommendations included at least hourly measurement of vital signs (VS) during infusion, daily electrocardiogram (EKG) before infusion, and contraindication in patients with previous CV comorbidities.

Objectives

To describe changes in VS and EKGs recordings in a cohort of RRMS patients during the first AL cycle treated at the same MS Center.

Methods

Since 2015, when AL was approved for MS in Italy, we consecutively monitored our patients for VS before and every 30 minutes during AL administration lasting at least 5 hours; EKGs were recorded daily before premedication. Methylprednisolone, chlorphenamine, acetaminophen, were given as premedication with ranitidine or omeprazole. We collected heart rate (HR), systolic (SBP) and diastolic blood pressure (DBP) after premedication, before AL infusion and every 60 minutes thereafter up to hospital discharge. Bradycardia was defined as HR<60 bpm or HR<20% if patient had bradycardia at day 1 admission. HR<45 bpm was the cut-off for clinically relevant bradycardia. Data about clinical history, comorbidities, and concomitant medications were collected.

Results

From June 2015 to November 2019, 47 (31 female) RRMS patients received the first AL course. At baseline mean age was 20.1(±8.1) years, disease duration 5.5(±5.5) years and EDSS 2 (0-4.5). 4 patients had CV comorbidities (2 hypertension, 2 premature ventricular contraction). A total of 153 EKGs were analyzed. We observed 30 non-specific repolarization abnormalities and 18 inverted T waves. Bradycardia was reported in 24 EKGs (20/24 at day 4 and 5). Bradycardia was recorded in 45/229 infusions. 24 patients showed at least 1 episode of bradycardia, 16/47 had clinically relevant bradycardia. SBP showed an increasing trend starting from the third day, but still within normal limits.

Conclusions

Our data support the need for accurate monitoring of AL infusion. AL administration was rarely associated with clinically relevant CV. Nevertheless, bradycardia was frequently recorded even though usually asymptomatic. Careful monitoring should be continued for the whole protocol of AL infusion since CV events can be observed independently from the expected early infusion-related reactions likely associated to cytokine release.

Collapse