Background

Yellow fever vaccine (YFV) is mandatory for travel in areas where yellow fever is endemic, but is not authorized for multiple sclerosis (MS) patients because of the potential risk of post-vaccine relapses. However, this recommendation is only based on a single study including 7 patients.

Objectives

The aim of the study is to assess the risk of worsening in relapsing remitting (RR) MS after YFV.

The primary objective was to compare the risk of relapse, during the 12 months after the YFV between exposed and non-exposed subjects. The secondary objectives were: (i) to assess the time to first relapse after YFV, using Kaplan-Meier curves. Hazard Ratio (HR) was estimated by an adjusted Cox model for EDSS score and for DMT at the time of YFV (ii) to compare the disability progression and the disease form 12 months after YFV, and at the end of the follow-up.

Methods

This is a non-interventional observational retrospective, exposed/non-exposed cohort study, nested in the French national cohort including MS patients. Exposed RR-MS patients received one subcutaneous dose of YFV. Each exposed subject was matched to 3 RR-MS non-exposed to YFV. The matching criteria were: age, sex and annualized relapse rate (ARR) for the year before vaccination. The risk of relapse during the 12 months after the YFV was compared between exposed and non-exposed subjects. The time to first relapse after YFV was assessed using Kaplan Meier curves; Hazard Ratio (HR) was estimated by an adjusted Cox model for EDSS score and for disease modifying therapy at time of YFV. The disability progression 12 months after the YFV was compared between exposed and non-exposed subjects.

Results

128 RR MS according to McDonald Criteria 2017 (32 exposed/96 non-exposed) were included. The ARR the year after YFV did not differ between exposed: 0.233 (0.430) and non-exposed subjects: 0.213 (0.511) (p=0.84). Time to first relapse was not different between the 2 survival curves (adjusted HR, 1.33; 95% CI 0.53-3.30, p=0.54). The disability progression over the year following YFV did not differ between exposed and non-exposed subjects (p=0.83).

Conclusions

YF vaccine, a live attenuated vaccine which is very effective, is required to enter the territory of endemic areas. French and US recommendations for immunization in MS concluded that « There is insufficient data in the literature to conclude on the potential risks related to yellow fever vaccine because studies are either lacking or insufficiently powered ».These results show that YFV doesn’t worsen RR-MS, and suggest that non-immunosuppressed RR-MS patients travelling to endemic areas for professional or personal reasons could be vaccinated against YF.