Is rheumatoid arthritis associated with reduced immunogenicity of the influenza vaccination? A systematic review and meta-analysis

Objective: To determine whether immunogenicity and safety of the influenza vaccination in rheumatoid arthritis (RA) patients are significantly different from those in a healthy population. Methods: PubMed, MEDLINE, Embase, Cochrane Library and Web of Science were searched on 31 August 2016. Studies were included when they met the inclusion criteria. Two reviewers independently extracted data on study characteristics, methodological quality and outcomes. The primary outcome was seroprotection (SP) rate after immunization. Results: Thirteen studies were included. The SP rates did not significantly differ between the RA patients and healthy controls for the H3N2 (RR = 0.96, 95% CI, 0.82 to 1.13, p = .64) and B strain (RR = 0.95, 95% CI 0.84 to 1. 08, p = .44). Nevertheless, RA was associated with a significant decrease in SP rate for the H1N1 strain (RR = 0.72, 95% CI 0.60 to 0.86, p < .001). RA patients receiving immunosuppressive chemotherapy, TNF blockers, rituximab and other biologics responded to the H1N1 strain significantly less than healthy controls in SP rate, whereas those receiving steroids did not. Non-adjuvanted vaccination had a significantly lower SP rate than in healthy controls, whereas adjuvanted vaccination did not. RA was associated with an increase in adverse events (RR = 1.77, 95% CI 1.02 to 3.08, p = .04). Conclusions: Immunogenicity was significantly different between RA patients and healthy controls for the H1N1 strain, but not for the H3N2 or B strains. Adverse event rates were higher in RA patients. Adjuvant and special kinds of immunosuppressive biologics may play an important role in immunogenicity of inactivated influenza vaccines for RA patients.