Safety and Efficacy of Eculizumab Therapy in Multiple Sclerosis: A Case Series.

Marco Allinovi,Vittorio Mantero,Angelo Bellinvia,Leonardo Caroti,Paolo Protopapa,Lorenzo Razzolini,Sabrina Milan Manani,Maria Pia Amato,Francesco Pesce,Calogero Lino Cirami,Lucia Del Vecchio,Brigida Brezzi

doi:10.3390/brainsci11101341

Abstract

(1) Background: Complement system activation has been proposed as one of the different factors that contribute to Multiple Sclerosis (MS) pathogenesis. In this study, we aimed to describe the potential effects of eculizumab, an anticomplement therapy, on MS disease activity in a cohort of relapsing–remitting (RR) MS patients who discontinued IFN-β therapy due to IFN-β-related thrombotic microangiopathy (TMA) onset. (2) Methods: In this retrospective observational multicentric study, we searched for all patients with MS treated by eculizumab with a survey of several nephrological and neurological centers (over 45 centers). (3) Results: Nine patients were included. The mean follow-up time under eculizumab was 3.72 ± 2.58 years. There were no significant differences in disease activity (EDSS, relapses, new T2, and/or Gd-enhancing lesions at MRI) considering the two years before and after eculizumab therapy. No adverse events potentially related to eculizumab therapy were reported during follow-up. (4) Conclusions: In this preliminary study, we described a good safety profile for eculizumab therapy in MS. However, the available data are not sufficient to make firm conclusions about the possible efficacy of eculizumab as a disease-modifying therapy for MS patients.

Highlights

We aimed to describe the potential effects of eculizumab treatment on the Multiple Sclerosis (MS) disease activity in a small sample of RRMS patients who had to stop treatment with
Five patients were excluded for an eculizumab therapy duration
This therapy has proved its efficacy in reducing relapses compared to a placebo in Neuromyelitis Optica Spectrum Disorder (NMOSD) patients [22], currently, there are no studies about treatments with eculizumab or other anticomplement therapies in MS

Summary

Introduction

Complement system dysregulation has been proposed as one of the different factors that could contribute to MS pathogenesis and clinical manifestations [3]. The complement system seems to have both a detrimental and a protective role on MS pathogenesis and the disease course [4]. Preclinical and clinical studies in the last decade have showed that the complement system has an established role in active plaque development [3]. Complement components can be used as biomarkers of disease state activity and response to treatment in MS patients [10], and drugs targeting complement activity might be potentially helpful in MS therapy [11]. Among different forms of TMA, thrombotic thrombocytopenic purpura (TTP) is characterized by deficient ADAMTS-13 activity, with atypical hemolytic uremic syndrome (aHUS) by the dysregulation of the complement system’s alternative pathway [16].

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Discussion

Conclusion