Anti-HBS titers are not decreased after treatment with oral cladribine in patients with multiple sclerosis vaccinated against hepatitis B virus

Landi, D.; Nicoletti, C.; Di Mauro, G.; Cola, G.; Grimaldi, A.; Mataluni, G.; Marfia, G.

Background and aims: Oral cladribine is a novel treatment for Multiple Sclerosis (MS). It is a purine nucleoside antimetabolite analogue that incorporates into the DNA, resulting in single-strand breaks in DNA and apoptosis of replicating lymphocytes. Specifically, Cladribine induces limited depletion of CD4 and CD8 T subsets and a more marked depletion of memory B cell subsets. Therefore, natural and acquired humoral response against pathogens may be potentially impaired. The aim of this study was to assess longitudinal variation of antiHBs titers in patients with MS treated with Cladribine. Methods: Patients with MS treated with 1 cycle of Cladribine (3,5 mg/kg) and previously vaccinated against Hepatitis B virus (HBV) were enrolled. Anti-HBs titers were compared pre and after 12 months from Cladribine treatment. Total lymphocyte count was also analysed. Results: Among the 14 RMS patients (11 F, mean age 33,7 SD 7) enrolled, all had anti-HBs titers >10 mg/dl at baseline. Anti-HBs titer dropped below the reference value (<10 mg/dl) at 12 months after Cladribine only in 1 case. Pre-post Cladribine mean anti-HBs values were not significantly different considering the whole cohort (Wilcoxon-Mann-Whitney Test p = 0,76). Four patients had grade 1 and 1patient grade 2 lymphocytopenia at 12 months. Conclusions: Cladribine does seem to reduce humoral immune responses in subjects previously vaccinated against HBV, even in case of drug-induced lymphocytopenia. These results, if confirmed in larger populations, appear reassuring also for other vaccinations (i.e. COVID19). The low impact of Cladribine on plasma cells may explain such findings.