Reduction of the risk of PML in natalizumab treated MS patients in Sweden: An effect of improved PML risk surveillance

Jan Lycke,Tomas Olsson,Anders Berglund,Anna Fält,Fredrik Piehl,Stina Kågström

doi:10.1016/j.msard.2021.102842

Abstract

BackgroundNatalizumab (NTZ) treatment of multiple sclerosis (MS) has been associated with increased risk of progressive multifocal leukoencephalopathy (PML). The aim of the present study was to evaluate the impact of PML risk assessment on PML incidence in NTZ treated MS patients. MethodsBy using information from the population-based Swedish MS registry a retrospective cohort was established of patients treated with NTZ between 2006-2018. The effect on PML incidence before and after utilizing a risk management plan, including JC virus (JCV) serology, was analyzed. ResultsIn December 2018, 804 PML cases associated with NTZ therapy of MS had been reported globally, including 9 cases from Sweden. The estimated PML incidence 2018 in Sweden and globally was 0.7 (0.3-1.4) and 4.15 (3.9-4.4) per 1,000 person years, respectively. In Sweden, JCV serology was introduced 2012 for PML risk assessment and the cumulative risk of PML was significantly lower 2012-2018 compared to the period 2006-2011 (p=0.042). The mean NTZ exposure time was 60.1 months (SD 37.2) in the first period (2006-2011) and 32.6 months (SD 22.0) in the second period (2012-2018). The number of patients treated with NTZ decreased, and the number of patients at increased risk of PML was 1.9 % at the end of the study period. ConclusionSince 2006 the incidence of PML associated with NTZ treatment of MS has decreased in Sweden. Our findings suggest that this reduction is due to an effective adoptation and adherence to the established risk management plan that implies switching patients at increased PML risk from NTZ to other highly efficacious therapies. A less pronounced decline in PML incidence has recently been observed in France, but not globally.

Highlights

Natalizumab (NTZ) is a humanized monoclonal antibody that inhibit leukocyte migration into the central nervous system (Yednock et al, 1992)
At study cut-off, 31 December 2018, 1,100 patients were currently treated with NTZ, of which 13% were JC virus (JCV)+
Mean JCV index for these patients was 0.86±0.92 and 112 patients had been treated for >24 months. Combinding these risk factors only 21 patients had a JCV index >0.9 and had been treated for >24 months i.e 1.9% (21/1100) patients was at incresed risk for progressive multifocal leukoencephalopathy (PML)

Summary

Introduction

Natalizumab (NTZ) is a humanized monoclonal antibody that inhibit leukocyte migration into the central nervous system (Yednock et al, 1992) It is approved for treatment of active relapsing-remitting multiple sclerosis (RRMS). Risk assessment was improved when pooled data from large observational studies was used to calculate the cumulative PML risk for patients on NTZ treatment according to their treatment exposure duration (Ho et al, 2017). Despite these improvements of PML risk assessment, the incidence of NTZ-associated PML has not decreased globally. Natalizumab (NTZ) treatment of multiple sclerosis (MS) has been associated with increased risk of progressive multifocal leukoencephalopathy (PML). A less pronounced decline in PML incidence has recently been observed in France, but not globally

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