Natalizumab, a valuable strategy for immunisation to avoid delays of treatment onset in highly active MS patients

ABSTRACT

Background: Vaccination during immunosuppression can result in impaired vaccine responses. In highly active patients requiring a rapid treatment initiation, vaccination can delay treatment onset. Natalizumab (NTZ) is a high-efficacy agent with potential low interference in vaccination responses, and could be a bridge therapy to achieve an adequate immunisation before starting another treatment. Objective(s) To assess the safety and immunogenicity of inactivated vaccines administered during NTZ treatment. Method(s) Self-controlled study based on an ongoing prospective cohort that included adult MS patients with complete immunisation schedules for hepatitis B vaccine (HBV), hepatitis A vaccine (HAV) and/or COVID-19 vaccine during NTZ treatment, between September 2016 and February 2022. Seroprotection rates were calculated for each vaccine. Demographic, clinical and radiological characteristics were collected the year before (pre-exposure period) and after vaccination (post-exposure period). Differences in annual relapse rate (ARR), contrast-enhancing lesions (CELs), new T2 lesions (NewT2) and changes in Expanded Disability Status Scale (EDSS) during pre and post exposure period were evaluated. Patients were also categorised according to time on NTZ exposure before vaccination (long-term exposure >1 year and short-exposure <=1 year) and according to JCV status. Result(s) From 248 patients treated with NTZ, 60 were vaccinated during NTZ exposure 44 (73%) women, mean age 45 years, mean disease duration 17 (SD 8.7) years. Thirty (50%) patients bridged to anti-CD20 after immunisation, because of high titers of JC virus. Between the pre and post-exposure period, we observed a decrease in both the AAR (0.28 vs 0.01;p=0.004) and newT2 (0.8 vs 0.02;p=0.1) and no changes in disability accumulation (EDSS 3.5 vs 3.5 p=0.6). The global seroprotection rate was 93% (91.6% (IC95% 73-99) for HAV (n=24), 92.6% (IC95% 76- 99) for HBV (n=27), 100% (IC95% 84-100) for Covid-19 (n=23)). No differences were seen between short and long term NTZ exposure or between JCV positive or negative patients, in terms of safety and immunogenicity. Conclusion(s) Immunisation with inactivated vaccines during NTZ treatment is safe and effective, both for short and long term NTZ exposure. In highly active PwMS who need immunisation, NTZ could be a valuable strategy to avoid delays in the onset of high-efficacy DMD, even in JC virus positive in which it could be used as a bridge therapy strategy.