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

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.