Objective T umour necrosis factor inhibitors (TN Fi) are effective in rheumatoid arthritis (RA), but disadvantages include adverse events (AEs) and high costs. This can be improved by disease activity-guided dose reduction (DR ). We aimed to assess long-term outcomes of TN Fi DR in RA by using 3-year data from the DR ESS study (Dose REduction Strategy of Subcutaneous TN F inhibitors study). Methods In the intervention phase (month 0-18) of the DR ESS study (Dutch trial register, NTR 3216), patients were randomised to DR or usual care (UC). In the extension phase (month 18-36), treatment strategies in both groups converged to continuation of protocolised tight control and allowed dose optimisation. Intention-to-treat analyses were done on flare, disease activity (28 joint count-based disease activity score with C reactive protein (DAS28-CRP )), functioning (health assessment questionnaire-disability index (HAQ-DI)), quality of life (Euroqol 5 dimensions 5 levels questionnaire (EQ5D-5L)), medication use, radiographic progression (Sharp van der Heijde score (SvdH)) and AE. Results 172/180 patients included in the DR ESS study were included in the extension phase. Cumulative incidences of major flare were 10% and 12% (-2%, 95% CI -8 to 15) in DR and UC groups in the extension phase, and 17% and 14% (3%, 95% CI -9 to 13) from 0 to 36 months. Cumulative incidences of short-lived flares were 43% (33 to 52%)%) and 35% (23 to 49%)%) in DR and UC groups in the extension phase, and 83% (75 to 90%)%) and 44% (31 to 58%)%) from 0 to 36 months. Mean DAS28-CRP , HAQDI, EQ5D-5L and SvdH remained stable and not significantly different between groups. TN Fi use remained low in the DR group and decreased in the UC group. Cumulative incidences of AE were not significantly different between groups. Conclusions Safety and efficacy of disease activity guided TNFi DR in RA are maintained up to 3 years, with a large reduction in TNFi use, but no other benefits. Implementation of DR would vastly improve the costeffective use of TNFi.