Tapering csDMARD or TNFi first: is the risk of flares different for ACPA-positive or ACPA-negative rheumatoid arthritis?

According to the European Alliance of Associations for Rheumatology (EULAR) recommendations, glucocorticoids should be tapered first, followed by biological DMARDs (bDMARDs) and conventional synthetic DMARDs (csDMARDs).1 In the total RA population, the optimal order of tapering (bDMARDs first or csDMARDs first) regarding clinical outcomes is not evident from the limited number of studies that have investigated this.2 3 As the RA population is heterogeneous, there might be patient factors that are relevant for the choice of tapering order. ACPA-positive but not ACPA-negative patients have shown to benefit from concomitant use of methotrexate with a tumour necrosis factor inhibitor (TNFi) compared with TNFi monotherapy.4 5 Thus, ACPA-positive patients might be at a higher risk of flares when combination therapy is discontinued compared with ACPA-negative patients. [...]we aimed to explore differences in flare rates between tapering strategies separately for ACPA-positive and ACPA-negative patients with RA with well-controlled disease using both a TNFi and a csDMARD. Flare-free survival curves for ACPA-positive (A) and ACPA-negative (B) patients with RA comparing a tapering csDMARD-first strategy (orange straight line) versus a TNFi-first strategy (blue dotted line), including 95% CIs. Noteworthy is the fact that we observed an equal risk of flares in the ACPA-positive and the ACPA-negative population, which was confirmed by the SEAM-RA (Study of Etanercept and Methotrexate in Combination or as Monotherapy in Subjects with Rheumatoid Arthritis) trial but contradictive to the results of the RETRO (Reduction of Therapy in patients with Rheumatoid arthritis in Ongoing remission) trial.7–9 Possibly, ACPA-negative patients who require biologicals are a selective group of ACPA-negative patients for which tapering treatment is more difficult than for those who do not require biologicals.