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Optimal time between the last methotrexate administration and seasonal influenza vaccination in rheumatoid arthritis: post hoc analysis of a randomised clinical trial
  1. Jin Kyun Park1,
  2. Yunhee Choi2,
  3. Kevin L Winthrop3,
  4. Yeong Wook Song1,
  5. Eun Bong Lee1
  1. 1 Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea
  2. 2 Division of Medical Statistics, Medical Research Collaborating Center, Seoul National University College of medicine, Seoul, Republic of Korea
  3. 3 Division of Infectious Diseases, Oregon Health and Science University, Portland, Oregon, USA
  1. Correspondence to Eun Bong Lee, Interanl Medicine, Seoul National University College of Medicine, Seoul 03080, Republic of Korea; leb7616{at}

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Methotrexate (MTX), a mainstay treatment for rheumatoid arthritis (RA), suppresses immune responses to influenza vaccination by approximately 15%–20%.1 To improve responses, MTX can be stopped or a higher dose of influenza antigen can be administered. A pilot study showed that holding MTX for 2 weeks before and 2 weeks after vaccination, or for 4 weeks after vaccination reversed MTX-induced suppression of vaccine responses, but with a tendency to increasing RA flare.2 A subsequent randomised clinical trial (RCT) showed that discontinuing MTX temporarily for 2 weeks after vaccination improved vaccine responses to an extent similar to those after discontinuation of MTX for 4 weeks, with no increase in RA disease activity.3 In the latter trial, patients skipped two doses of MTX after vaccination. Since levels of MTX in blood fall after the last dose, the time between the last MTX dose and vaccination may influence vaccine responses. Here, we examined clinical factors associated with improved vaccine responses after MTX discontinuation.

This is a post hoc analysis of the RCT that investigated the effect of MTX discontinuation for 2 weeks on responses to seasonal influenza vaccination.3 Briefly, 316 patients with RA …

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  • Contributors JKP, YC, KLW, YWS and EBL undertook data acquisition, analysis and interpretation and critical revision of the manuscript with respect to intellectual content. EBL had full access to all study data and takes responsibility for the integrity of the data and the accuracy of data analysis. JKP and EBL were responsible for study concept and design, and for drafting the manuscript.

  • Funding This study was sponsored by GC Pharma (formally known as Green Cross Corporation, Yongin-si, South Korea). The funder played no role in study design, data collection, data analysis, data interpretation or writing of the manuscript. The corresponding author had full access to all data and bears ultimate responsibility for the decision to submit for publication.

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

  • Patient consent for publication Not required.

  • 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. Written informed consent was obtained from all patients before enrolment in the trial. The study was registered with, protocol number: NCT02897011. The protocol allows use of stored sera for additional testing.