The likelihood of attaining and maintaining DMARD-free remission for various (rheumatoid) arthritis phenotypes

Abstract

Objectives: The objective of this study was to compare DMARD-free remission rates (DFRs) and sustained DFRs (SDFRs), defined as, respectively, DFR for ≥6 months and ≥1 year, after 2 and 5 years, between three clinical arthritis phenotypes: undifferentiated arthritis (UA), autoantibody-negative (RA-) and autoantibody-positive RA (RA+).

Methods: All UA (n = 130), RA- (n = 176) and RA+ (n = 331) patients from the tREACH trial, a stratified single-blinded trial with a treat-to-target approach, were included in the study. (S)DFR comparisons between phenotypes after 2 and 5 years were performed with logistic regression. Medication use and early and late flares (DAS ≥ 2.4), defined as at <12 months and >12 months after reaching DMARD-free remission (DFR), respectively, were also compared. Cox proportional hazard models were used to evaluate potential predictors for (S)DFR.

Results: Over the study periods of 2 and 5 years, less DFR was seen in RA+ (17.2-25.7%), followed by RA- (28.4-42.1%) and UA patients (43.1-58.5%). This also applied for SDFR over the 2- and 5-year periods in these three clinical arthritis phenotypes (respectively, 7.6% and 21.4%; 20.5% and 38.1%; and 35.4% and 55.4%). A flare during tapering was seen in 22.7% of patients. Of the patients in DFR, 7.5% had an early flare and 3.4% a late flare. Also, more treatment intensifications occurred in RA+ compared with RA- and UA. We found that higher baseline DAS, ACPA positivity, higher BMI and smoking were negatively associated with (S)DFR, while clinical phenotype (reference RA+), short symptom duration (<6 months) and remission within 6 months were positively associated with (S)DFR.

Conclusion: Long-term clinical outcomes differ between UA, RA- and RA+. These data reconfirm that RA can be subdivided into the aforementioned clinical phenotypes and that treatment might be best stratified upon these phenotypes, although validation is needed.

Trial registration: ISRCTN, https://www.isrctn.com/, ISRCTN26791028.

Keywords: anti-citrullinated protein antibodies; arthritis; autoantibodies; clinical phenotypes; rheumatoid arthritis; rheumatoid factor.