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Effect of short-term methotrexate discontinuation on rheumatoid arthritis disease activity: post-hoc analysis of two randomized trials

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Abstract

To investigate the effects of short-term discontinuation of methotrexate (MTX) on disease activity in patients with rheumatoid arthritis (RA) taking a stable dose of MTX. A post-hoc analysis of two randomized controlled trials was used to investigate the effects of temporary MTX discontinuation (for 2 weeks or 4 weeks) on responses to seasonal influenza vaccination. The impact of MTX discontinuation on the RA disease activity score (DAS28) and RA flare rate during discontinuation and after reintroduction was examined. The DAS28 increased during the 4-week MTX discontinuation period, before returning to baseline after reintroduction. The overall flare-free survival period did not differ between the groups (log rank p = 0.142). However, during the 4-week MTX discontinuation period, more patients in the MTX-hold group than in the MTX-continue group experienced a flare (20.5% vs. 7.4%, respectively; p = 0.058). After resumption of MTX, the flare rate did not differ between groups. The flare rates in the MTX-continue group and the 2-week and 4-week MTX-hold groups were 5.8%, 10.8% and 20.5%, respectively (p < 0.01). The change in the DAS28 from baseline did not differ significantly between the MTX-continue and the 2-week MTX-discontinue groups. However, there was a significant difference between the 4-week MTX-hold group and the MTX-continue group (p = 0.005). Short-term discontinuation of MTX for up to 2 weeks is safe, whereas discontinuation for 4 weeks is associated with a transient increase in disease flares and activity in RA patients taking a stable MTX dose.

Key Points

• Methotrexate discontinuation for 2 weeks is safe.

• Methotrexate discontinuation for 4 weeks transiently increases flare risk and disease activity.

• Disease flare risk and disease activity return to baseline after restarting methotrexate treatment.

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Acknowledgements

We thank Drs Yun Jong Lee, Kichul Shin, You-Jung Ha and Eun Young Lee for their critical contributions to the study. We also thank all study participants for their support.

Funding

The work was supported by GC Pharma (Yongin-si, South Korea).

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Authors and Affiliations

  1. Division of Rheumatology, Department of Internal Medicine, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul, 03080, South Korea

    Jin Kyun Park, Min Jung Kim, Yeong Wook Song & Eun Bong Lee

  2. Division of Medical Statistics, Medical Research Collaborating Center, Seoul National University College of Medicine, Seoul National University Hospital, Seoul, South Korea

    Yunhee Choi

  3. Division of Infectious Diseases, Oregon Health and Science University, Portland, OR, USA

    Kevin Winthrop

Authors
  1. Jin Kyun Park
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  2. Min Jung Kim
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  3. Yunhee Choi
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  4. Kevin Winthrop
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  5. Yeong Wook Song
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  6. Eun Bong Lee
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Contributions

Study concept and design: Jin Kyun Park and Eun Bong Lee.

Acquisition, analysis or interpretation of data: Jin Kyun Park, Min Jung Kim, Yunhee Choi, Yeong Wook Song, Kevin Winthrop and Eun Bong Lee.

Drafting of the manuscript: Jin Kyun Park and Eun Bong Lee.

Critical revision of the manuscript for important intellectual content: Jin Kyun Park, Min Jung Kim, Yunhee Choi, Yeong Wook Song, Kevin Winthrop and Eun Bong Lee.

Statistical analysis: Eun Bong Lee, Jin Kyun Park, Min Jung Kim, Yunhee Choi and Kevin Winthrop.

Obtained funding: Eun Bong Lee.

Study supervision: Eun Bong Lee.

Corresponding author

Correspondence to Eun Bong Lee.

Ethics declarations

All patients gave written informed consent, and ethical approval was obtained.

Disclaimer

The funder played no role in study design, data collection, data analysis, data interpretation or writing of the report. The corresponding author had full access to all study data and takes ultimate responsibility for the decision to publish.

Conflict of interest

EBL has acted as a consultant to Pfizer. The other authors have no conflicts of interest to declare.

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Park, J.K., Kim, M.J., Choi, Y. et al. Effect of short-term methotrexate discontinuation on rheumatoid arthritis disease activity: post-hoc analysis of two randomized trials. Clin Rheumatol 39, 375–379 (2020). https://doi.org/10.1007/s10067-019-04857-y

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  • DOI: https://doi.org/10.1007/s10067-019-04857-y

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