Background The effectiveness of TNF-inhibitors (TNFi) in the treatment of rheumatoid arthritis has been demonstrated in many studies . However, little is known on stopping TNFi in patients with stable low disease activity and the subsequent likelihood of exacerbation of rheumatoid arthritis (RA). In addition, it is not clear whether TNFi can be restarted effectively and safely. Given the costs and risks , it is important to examine whether patients in stable low disease activity can effectively stop TNFi.
Objectives To assess whether RA-patients in stable remission or low disease activity (DAS28<3.2) can effectively and safely stop and restart TNFi.
Methods Multicenter open-label randomized controlled trial. Patients diagnosed with RA according to the ACR 1987 criteria were included. Patients had been treated with a TNFi for at least 1 year and with stable dose DMARDs for at least 6 months. All included patients had low disease activity in the 6 months prior to inclusion, with at least 2 DAS28 scores <3.2 in this period. Patients were randomized to stop or continue their current TNFi in a 2:1 ratio. DAS28 flare was defined as DAS28 ≥3.2 with an increase ≥0.6 compared to the previous DAS28.
Results In total 817 patients from 47 centers were included: 531 (65%) patients were randomized to the stop group and 286 (35%) to TNFi continuation. All included patients had low disease activity in the 6 months prior to inclusion, with at least 2 DAS28 scores <3.2 in this period and 81.1% was in remission (DAS28<2.6). At 6 months, significantly more patients in the stop group had experienced a DAS28 flare versus the continuation group (29.3% vs 9.7% respectively, p<0.0001). At 12 months these were 40.8% vs 14.4% respectively, p<0.0001. Flare free survival was significantly lower in the stop group (p<0.0001), with a median time to first flare of 24 weeks in those that flared. The adjusted hazard ratio for flare after stopping TNFi was 3.19 (95% CI: 2.26–4.50). Of the patients that restarted TNFi within the first 26 weeks after stopping, already 83% had regained DAS28<3.2 six months later and median survival time to regained DAS28<3.2 was 12 weeks (95% Cl 10.9-13.1).
Conclusions 59% of RA-patients with stable remission or low disease activity (DAS28 <3.2) can stop TNFi without flare in 12 months follow up. The data suggest that TNFi can be restarted effectively and safely.
Nam JL, Winthrop KL, van Vollenhoven RF, et al. Current evidence for the management of rheumatoid arthritis with biological disease-modifying antirheumatic drugs: a systematic literature review informing the EULAR recommendations for the management of RA. Ann Rheum Dis 2010;69:976–86.
Ramiro S, Gaujoux-Viala C, Nam JL, et al. Safety of synthetic and biological DMARDs – a systematic literature review informing the 2013 update of the EULAR recommendations for management of rheumatoid arthritis. Ann Rheum Dis 2013; submitted.
Disclosure of Interest None declared