Tetanus and Diphtheria Toxoid-Containing Vaccine in Multiple Sclerosis Patients: A Real-World Prospective, Open-Label, Multi-Centre Study

<b>Objective</b>: To assess changes in disease activity in Multiple Sclerosis (MS) patients on various disease-modifying-drugs, as well as immunogenicity, safety and clinical tolerability following combined tetanus- and diphtheria-vaccination. <b>Methods</b>: We conducted a prospective, multicentre, non-randomised real-world observational study at specialised outpatient MS care centres in Germany. We enrolled multiple sclerosis patients receiving a combined tetanus- and diphtheria-vaccination who had a stable MS-treatment regimen for at least six months and had an indication for this vaccination. Serum samples were obtained before and four weeks after vaccination for specific antibody response. Antibody concentrations against vaccine antigens were measured in duplicate via ELISA. Subjects were followed for one year after immunisation. MS disease activity (EDSS and relapse rates) was evaluated at follow-up visits. Local and systemic adverse events were registered four weeks after vaccination. <b>Results</b>: In total, 72 MS patients received tetanus and diphtheria vaccination. The annualised relapse rates in the year after vaccination were comparable to the year before vaccination (0.39 vs. 0.37). During the study period, the EDSS score did not change significantly. The score was 2.0 and 2.2 in the two years prior to vaccination and 2.5 in the year following vaccination. No subjects experienced severe adverse events. However, 14 (19.4%) had local adverse events, and 10 (13.9%) had systemic reactions. Following vaccination, all subjects had protective antibody titres against tetanus- and diphtheria-toxoid. Geometric mean antibody titres of tetanus toxoid antibodies increased from 0.64 IU/mL to 2.23 IU/mL (<i>p</i> < 0.0001) and of diphtheria toxoid antibodies from 0.1 IU/mL to 0.45 IU/mL (<i>p</i> < 0.0001). <b>Conclusions</b>: Tetanus- and diphtheria vaccination proved to be safe and effective in MS patients in a real-world situation.