Résumé
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, immu- nogenicity to PCV13 under abatacept is similar to PPSV23. There were no unexpected side effects after pneumococcal vaccines.