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

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.

Thrombotic microangiopathy due to acquired complement factor I deficiency in a male receiving interferon‐beta treatment for multiple sclerosis

“…A previous published report identified an underlying genetic causative complement factor in a case of IFNβ‐associated TMA 13 . In this report, two arguments support the hypothesis of an acquired incomplete deficiency of factor I due to antibodies generated by IFNβ.…”

“…A previous published report identified an underlying genetic causative complement factor in a case of IFNβ-associated TMA. 13 F I G U R E 1 Mesangial fibrosis with mesangiolysis and reduction of the lumen of glomerular capillaries (trichrome staining Â40) (A, arrow). Segmental fibrinoid necrosis in a glomerulus (trichrome staining Â40) (B, arrow).…”

Thrombotic Microangiopathy as a Life-Threatening Complication of Long-Term Interferon Beta Therapy for Multiple Sclerosis: Clinical Phenotype and Response to Treatment—A Literature Review

“…However, among patients with severe IFNβ-related TMA and stage 3 AKI, eculizumab seems to be associated with a lower incidence of ESKD, which further support the role of the complement system in the pathogenesis of these forms. Therefore, eculizumab could represent an effective therapy for INFβ TMA forms, like that noted for other severe secondary TMA forms [ 11 , 63 ].…”

“…The occurrence of TMA has been described in a few patients under treatment with IFNβ, mostly as individual case reports or small case series [ 9 , 10 , 11 ]. Intriguingly, a recent study described a dose-dependent toxic effect of the IFNβ on the microvasculature [ 12 ], suggesting a role of this therapy in endothelial damage, which may result in TMA, thus challenging the hypothesis of a fortuitous association.…”

Drug-induced thrombotic microangiopathy: An updated review of causative drugs, pathophysiology, and management

“…Several case report and little case series suggested the effectiveness of C5-inhibitor in DITMA in terms of normalization of hematological parameters and, in some cases, partial or complete recovery of kidney function ( Allinovi et al, 2017 ; Cavero et al, 2017 ; Caravaca-Fontan and Praga, 2019 ; Grall et al, 2021 ). In particular, eculizumab proved its efficacy in three out of 9 (33.3%) patients who resolved the IFN-related TMA without further complications, and in four out of six patients who needed dialysis treatment at DITMA onset and discontinued dialysis after a mean of 2 months of eculizumab treatment ( Allinovi et al, 2021 ). Moreover ( Grall et al, 2021 ), reported a significantly better kidney response (83% vs. 64% of complete/partial recovery) and kidney outcome (eGFR 45 vs. 33 ml/min/1.73) in 13 patients with gemcitabine-induced TMA treated with anti-complement therapy.…”