Pos1068 humoral immune response to 13 valent-conjugate and 23-valent polysaccharide pneumococcal vaccines in ra patients treated with abatacept: results of the open randomized controlled trial vacina (vaccination against pneumococcal in naïve abatacept rheumatoid arthritis patients)

Background To prevent infections, EULAR recommends to vaccinate RA patients against streptococcal pneumoniae. It is recommended to vaccine with the conjugate vaccine (PCV13) followed by a dose of PPSV23 at least 8 weeks later. PCV13 is a T- cell dependent vaccine whereas PPSV23 induces a T-independent humoral response. Abatacept is a biological DMARD that inhibits T cell activation. Objectives We hypothesized that the humoral response may be more affected under abatacept after PCV13 vaccination than after PPSV23. To adress this question, we compared the humoral response four weeks after vaccination with PCV13 or PPSV23 in RA patients treated with abatacept. Methods We conducted a prospective, multicenter, randomized, open-label study in patients with RA according to ACR/EULAR 2010 criteria, and starting abatacept because of inadequate response to MTX or leflunomide (DAS28>3,2). Patients were randomized in 2 groups: the first group (G1) was vaccinated with the PPSV23 and the second group (G2) with PCV13 and PPSV23 8 weeks later. Abatacept was to be started on the same day as the first vaccine (PCV13 or PPSV23). Patients having been treated previously with rituximab within the last year were excluded. A patient was considered as responder if there was a two-fold increase in the antibodies titer measured by ELISA for at least 3 of 5 serotypes of interest (1, 3, 14, 7F, 19A) which are the most frequently involved in pneumococcal infections. For the primary endpoint, we compared the rate of responders at one month in G1 and G2 using a Chi-Square test. Sample size calculation based on alpha risk 5% and 80% power requirements resulted in 80 patients. Tolerance of the vaccines were collected within the first week and later in a patient booklet. Adverse events were also collected at 1, 2, 6 and 12 months. Results Eighty patients were included and randomized in the two groups: 40 in G1 and 40 in G2 (1 patient withdrew his consent before any treatment in G2). Characteristics of patients are described in Table 1. Female were more represented in G1 (82.5%) compared to G2 (64.1%). Lymphocyte count were significantly higher in G1 compared to G2: 1841/uL (+/-887) vs 1603/uL (+/-580). In the mITT, the rate of responders was 47.5% in in G1 and 38.46% in G2 (p=0.42) with a RR of 1.23 (IC95%: 0.73-2,06; when comparing responders in PPSV23 vs PCV13 groups. This absence of difference was confirmed with a per protocol analysis (p=1) and after adjusting for gender and lymphocytes count with a logistic regression test (RR=1.6 IC95% 0.6-4.2). 17 infections were reported in G1 and 28 in G2 with 3 severe infections but no pneumococcal infection. Conclusion In RA patients treated with abatacept combined with sDMARDs (MTX or LEF), the rate of responders is similar 28 days following vaccination with PCV13 or PPSV23. Although PCV13 is a T cell dependent vaccine, immunogenicity to PCV13 under abatacept is similar to PPSV23. There were no unexpected side effects after pneumococcal vaccines. Table 1. Characteristics of patients at inclusion Variable Modality All population N=79 Group1 PPSV23 N=40 Group 2 PCV 13 N=39 Age (years ) Mean (±SD) 59.61 (± 12.59) 58.08 (± 13.74) 61.18 (± 11.24) Gender Women 58 (73.42) 33 (82.50) 25 (64.10) BMI (kg/m² ) Mean (±SD) 26.03 (± 5.09) 26.76 (± 6.17) 25.29 (± 3.62) Previous pneumocccal vaccine Yes/ (%) 17 (21.52) 10 (25.00) 7 (17.95) DAS28 CRP Mean (±SD) 4.33 (± 0.90) 4.20 (± 0.79) 4.46 (± 1.00) RF positive Yes/ (%) 55 (70.51) 30 (75.00) 25 (64.10) ACPA positive Yes/ (%) 55 (70.51) 31 (77.50) 24 (61.54) Erosive RA Yes/ (%) 47 (61.04) 24 (60.00) 23 (58.97) Lymphocytes count n/uL Mean (±SD) 1822.31 (± 778.25) 2029.73 (± 886.68) 1603.97 (± 579.90) MTX Yes/ (%) 63 (79.75) 32 (80.00) 31 (79.49) MTX dose (mg/w ) Mean (±SD) 15.67 (± 4.52) 15.63 (± 5.12) 15.73 (± 3.88) Leflunomide Yes/ (%) 8 (10.13) 4 (10.00) 4 (10.26) Steroids Yes/ (%) 33 (41.77) 16 (40.00) 17 (43.59) Steroid dose (mg/d ) Mean (±SD) 7.77 (± 2.42) 7.50 (± 2.58) 8.03 (± 2.30) Acknowledgements We thank the Bristol Myers Squibb and the French Society of Rheumatology for an unrestricted grant. Disclosure of Interests Jacques Morel Speakers bureau: Amgen, Biogen, Bristol Myers Squibb, Fresenius Kabi, Janssen, Lilly, Merck Sharp and Dohme, Medac, Mylan, Nordic Pharma, Novartis, Pfizer, Roche Sanofi, Sandoz, Union Chimique Belge, Consultant of: Abbvie, Boerhinger Ingelheim, Galapagos, Glaxo Smith Kline, Pfizer, Grant/research support from: Pfizer, Novartis, Bristol Myers Squibb, Lilly, Olilvier Brocq: None declared, Cécile Gaujoux-Viala: None declared, Arnaud Constantin: None declared, Slim Lassoued: None declared, Emmanuelle Dernis: None declared, Christophe Richez: None declared, Cédric Lukas: None declared, Claire Daien: None declared, Claire Duflos: None declared.