Background One of the most effective strategies to prevent infections is vaccination, especially in patients treated with biologics and immunosuppressive (IS) agents. Nevertheless, the effectiveness of the resulting immune response in these patients has been questioned.
Objectives To perform a systematic literature review aiming to assess evidence available regarding immune response efficiency (IRE) and the ideal schedule for vaccination in RA and SpA patients treated with Methotrexate (MTX), TNF inhibitors (TNFi), anti-CD20 (rituximab, RTX), anti-CTLA4 (abatacept, ABA) or anti-IL6 (tocilizumab, TCZ).
Methods A systematic literature review was conducted by searching in PubMed all studies with the MeSH terms “[Rheumatoïd Arthritis” OR “Spondyloarthritis”] AND [“vaccination” OR “vaccines”] AND [“Methotrexate” OR “Abatacept” OR “Tocilizumab” OR “Rituximab” OR “Adalimumab” OR “Certolizumab” OR “Etanercept” OR “Golimumab” OR “Infliximab”], with no limitation regarding time of publication. Only studies evaluating the IRE were included. Case reports, general reviews and meta-analysis were excluded.
Results After exclusion criteria, 35 studies (out of 60 studies retrieved) assessing IRE in RA or SpA patients were selected, under MTX (n=35), TNFi (n=18), RTX (n=8), ABA (n=4) or TCZ (n=5). The studied vaccines were mostly the trivalent seasonal Influenza (n=20), the anti-pneumococcal vaccine (n=16), and few studies regarding the tetanus toxoid vaccine (TTV) (n=2), Hepatitis A vaccine (n=1) and accidental revaccination against yellow fever (n=2). Most studies (32/35) evaluated the IRE using the antibody (Ab) titer. When studying the anti-pneumococcal and influenza vaccination, the primary outcome was mainly the seroresponse 3 to 6 weeks after vaccination (i.e. Ab ratio post/pre-vaccine) but some studies (15/35) also assessed the seroprotection rate (i.e. patients with an effective titer of protective Ab), and some (3/35) the effectiveness of seroresponse using the opsonization index rate.
Regarding the anti-pneumococcal and influenza vaccination, MTX, RTX, and ABA were reported to impair the immune response; neither TNFi nor TCZ were shown to decrease seroresponse.
Regarding TTV, one study showed persistent seroresponse in patients treated with TNFi; a second study showed no difference between MTX and RTX in response to T-cell dependant protein Ag TTV.
Two studies reported no significant difference in efficiency or tolerance in patients accidentally revaccinated against yellow fever under TNFi.
Conclusions These observations highly suggest that an effective vaccination for patients treated with MTX, RTX, and ABA should necessitate a therapeutic window or a scheduled treatment spacing, in order to offer the best protection against Influenza and Pneumococcal infection. This might not be necessary in patients under TNFi or TCZ; nevertheless, further studies are necessary to optimize the vaccination modalities.
Disclosure of Interest None declared