Interaction between B-cell activation factor and methotrexate impacts immunogenicity of seasonal influenza vaccination in patients with rheumatoid arthritis

Methotrexate (MTX) with its proven efficacy and safety profile remains as the anchor drug for the treatment of rheumatoid arthritis (RA).1 2 However, the impact of MTX alone or in conjunction with antitumour necrosis factor (anti-TNF) on humoral immune system and infection risk varies markedly among patients with RA, suggesting that other host factors influence the therapeutic response to MTX and/or anti-TNF treatment.3 A possible candidate is B-cell activating factor (BAFF), which promotes B-cell activation and differentiation for antibody production.4 When patients with RA received anti-TNF treatment, a high BAFF serum level prevented formation of antidrug antibody in patients taking MTX but not those who did not.5 Thus, in the presence of MTX, BAFF may exert a paradoxical anti-inflammatory effect. Here, we investigated whether high BAFF levels negatively impact vaccine response via the inhibitory BAFF–MTX interaction in patients with RA taking MTX. Patients with RA according to the revised 1987 American College of Rheumatology from the randomised controlled trial (ClinicalTrials.gov identifier: NCT02897011) that aimed to investigate the effects of a 2-week MTX discontinuation on vaccine response to seasonal influenza vaccination were included in this study.6 Patients with RA were randomised to continue MTX or to hold …