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Interaction between B-cell activation factor and methotrexate impacts immunogenicity of seasonal influenza vaccination in patients with rheumatoid arthritis
  1. Jin Kyun Park1,
  2. Ye Ji Lee1,
  3. Samuel Bitoun2,
  4. Kevin L Winthrop3,
  5. Yunhee Choi4,
  6. Eun Bong Lee1,
  7. Xavier Mariette2
  1. 1 Division of Rheumatology, Department of Internal Medicine, Seoul National University, Seoul, Korea
  2. 2 Rheumatology Department, Université Paris-Sud, INSERM UMR1184, Immunology of Viral Infections and Autoimmune Diseases, Hôpitaux Universitaires Paris-Sud-Assistance Publique-Hôpitaux de Paris (AP-HP), Le Kremlin Bicêtre, France
  3. 3 Division of Infectious Diseases, Oregon Health and Science University, Portland, Oregon, USA
  4. 4 Division of Medical Statistics, Medical Research Collaborating Center, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, Korea
  1. Correspondence to Professor Xavier Mariette, Service de Rhumatologie, Hôpitaux, Universitaires Paris-Sud 78, Paris 94270, France; xavier.mariette{at}

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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 ( 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 …

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  • YJL and SB contributed equally.

  • Handling editor Josef S Smolen

  • Contributors JKP, YJL, SB, KLW, YC, EBL and XM contributed to the acquisition, analysis or interpretation of data and critical revision of the manuscript for important intellectual content. XM had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. JKP, EBL and XM were responsible for the study concept and design and drafting of the manuscript.

  • Funding This study was sponsored by GC Pharma (formally known as Green Cross Corporation, Yongin-si, South Korea).

  • Competing interests EBL has acted as a consultant to Pfizer and received research grants from GC Pharma and Hanmi Pharm.

  • Patient consent Obtained.

  • Ethics approval The study was approved by the Institutional Review Board of the Seoul National University Hospital (IRB 1608-158-787) and was conducted in accordance with the principles of the Declaration of Helsinki and Good Clinical Practice guidelines. The study was registered with, protocol number: NCT02897011. The protocol allows to use the stored sera for additional testing.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data statement The corresponding author had full access to all the data in the study and final responsibility for the decision to submit for publication.