Experiences in treatment of multiple sclerosis with natalizumab from a real-life cohort over 15\xa0years

Michael Auer,Elena Fava,Anne Zinganell,Florian Deisenhammer,Harald Hegen,Thomas Berger,Franziska Di Pauli,Klaus Berek,Gabriel Bsteh,Sebastian Wurth

doi:10.1038/s41598-021-02665-6

Abstract

Natalizumab (NTZ) has been used for treatment of highly active relapsing–remitting multiple sclerosis (MS). When stopping NTZ the risk of severe rebound phenomenon has to be considered. We aimed to investigate the use of NTZ in clinical routine and focused on identification of potential risk factors for disease reactivation after treatment discontinuation. At the Medical University of Innsbruck, Austria, we identified all MS patients who were treated with NTZ and performed a retrospective analysis on therapeutic decision making, disease course before, during and after treatment with NTZ and on risk factors for disease reactivation after NTZ discontinuation. 235 NTZ treated MS patients were included, of whom 105 had discontinued treatment. At NTZ start disease duration was 5.09 (IQR 2.09–10.57) years, average number of total relapses was 4 (IQR 3–6) and median EDSS 2.0 (range 0–6.5), whereby these values significantly decreased over time. Reduction of annualized relapse rate (ARR) on treatment was 93% and EDSS remained stable in 64%. In multivariate regression models only conversion to secondary progressive MS (SPMS) on treatment was significantly associated with lower risk of disease reactivation after NTZ, while ARR before treatment was associated with earlier disease reactivation. We could confirm the high therapeutic efficacy of NTZ which trends to be used earlier in the disease course nowadays. Discontinuation of NTZ seems safe only in patients who convert to SPMS during treatment, while higher ARR before NTZ increases the risk of disease reactivation after treatment discontinuation.

Highlights

Natalizumab (NTZ) has been used for treatment of highly active relapsing–remitting multiple sclerosis (MS)
At the Medical University of Innsbruck (MUI), Austria, from 2006 to December 2020, a total of 242 patients were treated with NTZ, all of whom had a relapsing–remitting disease course at treatment start
With this retrospective cohort analysis, we aimed to describe the use of NTZ, its efficacy and the risk factors for disease reactivation after discontinuation in clinical practice outside of controlled studies

Summary

Introduction

Natalizumab (NTZ) has been used for treatment of highly active relapsing–remitting multiple sclerosis (MS). Natalizumab (NTZ) is a humanized monoclonal antibody used for treatment of highly active relapsing remitting multiple sclerosis (MS). NTZ has been increasingly used in patients with a highly active disease course with at least two relapses within one year and according magnetic resonance imaging (MRI) findings, or mostly in patients where other disease-modifying treatments (DMT) like interferon-beta and glatirameracetate did not demonstrate sufficient therapeutic e ffectiveness[4]. Highly effective therapeutic options were approved in recent years and awareness has been raised regarding the risk of disease reactivation after NTZ discontinuation[12,13], safe strategies for switching from NTZ to other DMTs14, such as B cell-depleting t herapies[15], have been sought. While NTZ is a well-studied drug with reliable data from clinical trials, analysis of a real-life cohort could add important insights about the use of NTZ in clinical routine and how the disease develops before, during and after NTZ treatment and could identify risk factors for disease reactivation after stopping NTZ

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