Background/Purpose: Disease modifying antirheumatic drug (DMARD)-free sustained remission, the sustained absence of arthritis after cessation of all DMARD-therapy, is increasingly achievable with current treatment strategies. It is a proxy of cure of RA and also signifies normalisation of functional status. Absence of ACPA is an important predictor. Nonetheless, ≤10% of ACPA positive patients currently achieves this outcome. It has recently been suggested that immunological remission, defined as disappearance of ACPA and RF, is a proxy of cure.(Schett G, ARD, 2016) We performed a long-term observational study in ACPA and/or RF positive patients to determine if these autoantibodies disappear in patients who achieve DMARD-free sustained remission, thus after having developed the best possible clinical outcome.

Methods: Of 1587 RA patients (970 RF and/or ACPA positive) included in the Leiden Early Arthritis Clinic, 339 (21%) achieved DMARD-free sustained remission. Of these, 117 (35%) were ACPA and/or RF positive at diagnosis and were studied. In addition 22 autoantibody positive RA patients who experienced a late flare after having been in DMARD-free remission for 2.4 years were studied. As control, 50 autoantibody positive RA patients who were unable to stop DMARD therapy, were evaluated. DMARD-free sustained remission was achieved after a median follow-up of 4.5 years. Median total follow-up was 13 years. ACPA and RF levels were determined in serial samples, at least at baseline and at and/or after achieving DMARD-free remission.

Results: 12.8% of ACPA positive RA patients who achieved DMARD-free sustained remission, had converted to ACPA-negativity at achieving remission (Figure). However within RA patients with a late flare or with persistent disease and similar follow-up duration this occurred in 8.3% and 5.7%, respectively (p=0.56). For RF similar results were observed. RF positive RA patients who achieved DMARD-free sustained remission had seroconversion to RF-negativity in 19.7%, whereas this also occurred in 14.6% of RF positive RA patients with persistent disease. Evaluating the estimated slope of serially measured levels revealed that the RF levels decreased significantly more in patients that achieved DMARD-free sustained remission compared to those that did not (p<0.001). Within ACPA-positive patients however, there was no enhanced decrease in ACPA levels (p=0.66).

Conclusion: DMARD-free sustained remission is achieved in 12% of RA patients that were autoantibody positive at diagnosis. Only a minority had converted to seronegativity when DMARD-free sustained remission was achieved; this proportion was not different from that in patients with persistent disease. The finding that ACPA remains present in RA patients with sustained absence of arthritis and normalized function after DMARD-cessation suggests that immunological remission, defined as disappearance of ACPA, probably should not be a treatment target.