THU0149 PRIME-BOOSTER RESPONSE TO PNEUMOCOCCAL CONJUGATE AND POLYSACCHARIDE VACCINES IN PATIENTS WITH INFLAMMATORY RHEUMATIC DISEASES
Authors: Per Nived, Göran Jönsson, Bo Settergren, Jon Einarsson, Tor Olofsson, Johan K Wallman, Charlotte Sværke Jørgensen, Meliha C Kapetanovic
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> A vaccination using a combination of a dose of 13-valent pneumococcal conjugate vaccine (PCV13) followed by a dose of 23-valent polysaccharide vaccine (PPV23) after at least 8 weeks is currently recommended for the immunosuppressed patients with rheumatic diseases. <h3>Objectives</h3> To explore if the prime-booster vaccination strategy using the combination of PCV13 + PPV23 improves antibody response compared to PCV alone in immunosuppressed patients with inflammatory rheumatic diseases, and to compare with the prime-booster response in patients not treated with disease modifying anti-rheumatic drugs (DMARDs) and controls. <h3>Methods</h3> In total, 45 patients treated with rituximab (rheumatoid arthritis (RA)/arthritis=35 and vasculitis=10), 20 RA patients on abatacept; 27 patients on methotrexate/azathioprine/mycophenolate mofetil (MTX/AZA/MMF; RA=14 and vasculitis=13); 17 patients without DMARDs (RA/arthritis=12 and vasculitis=5) and 25 healthy controls participated. Only patients on an unchanged dose of DMARDs for at least 4 weeks before vaccination were eligible for the study. All participants were vaccinated with a dose PCV followed by a dose PPV23 after at least 8 weeks. A subgroup of rituximab treated patients had been vaccinated earlier with either 7-valent pneumococcal conjugate vaccine (PCV7) or PCV13. Blood samples were taken immediately before and 4-6 weeks after each vaccine dose. Pneumococcal serotype-specific antibodies to the 12 serotypes common to both vaccines were analyzed using a multiplex bead array assay (Luminex). Positive antibody response was defined as at least 2-fold increase in prevaccination serotype-specific antibody concentration. Number of serotypes with positive antibody response after prime-booster vaccination were compared between treatment groups and controls using Mann-Whitney U test. In addition, the difference in number of serotypes with positive antibody response between prime and prime-booster vaccination in each treatment group was compared using Wilcoxon signed<i>-</i>ranks test. <h3>Results</h3> Compared to PCV alone, the combined schedule with PCV+ PPV23 resulted in increased antibody response for patients treated with abatacept, MTX/AZA/MMF, and controls (all <i>p</i>≤0.01). In patients with rituximab and previous PCV7 or PCV13, booster vaccination with PPV23 did not result in increased antibody levels (Figure: bars marked grey). The numbers of serotypes with a positive antibody response to the combined vaccination with PCV + PPV23 was reduced in patients with rituximab (median 1, <i>p</i>≤0.001), abatacept (median 7, <i>p</i>≤0.001) and MTX/AZA/MMF (median 9, <i>p</i>≤0.001), but not in patients without DMARDs (median 10, <i>p</i>=0.12), compared to controls (median 11). <h3>Conclusion</h3> Prime-booster vaccination strategy using a combination of a dose of pneumococcal conjugate vaccine followed by a dose of polysaccharide vaccine improved antibody responses in patients with inflammatory rheumatic disease treated with abatacept and traditional DMARDs compared to PCV alone. The combined vaccination resulted in a markedly lower response in rituximab treated patients, and was to a lesser degree reduced in patients with abatacept or traditional DMARDs compared to healthy controls. <h3>Disclosure of Interests</h3> Per Nived: None declared, Göran Jönsson: None declared, Bo Settergren: None declared, Jon Einarsson: None declared, Tor Olofsson: None declared, Johan K Wallman Consultant for: Consultant for AbbVie, Celgene, Eli Lilly, Novartis, and UCB Pharma., Charlotte Sværke Jørgensen: None declared, Meliha C Kapetanovic: None declared