The likelihood of attaining and maintaining DMARD-free remission for various (rheumatoid) arthritis phenotypes
Authors: Luurssen-Masurel Nathalie , van Mulligen Elise , Weel-Koenders Angelique Elisabeth Adriana Maria , Hazes Johanna Maria Wilhelmina , de Jong Pascal Hendrik Pieter ,   the tREACH group investigators,   the tREACH group, Aartsen R C , Alfenaar C , Alves R , Arendse M , Arnoldus M , Baak-Dijkstra J , Bal-overzier P , Barendregt N , Basoski S , Beer D , Berkel F , Bonte M , Born van den D , Breukelen van S , Bron H , Buijs N , Buijs M , Cambier D , Cateten S , Claessen E , Colin A , Dekker R , Dolhain M , Donze F , Fodili A , Gerards G , Goudeketting B , Grillet de H , Haasnoot B , Hamelink K , Han J , Hazes Y , Houdt van L , Hove van M , Huisman J , Jager de M , Jager de J , Jasperse C , Jonkers S , Joziasse C , Kaal-Alfenaar K , Klootwijk T , Krommenhoek M , Krugten van T , Kuijper W , Lam Tse H , Leemput van C , Legierse M , Lenssinck P , Lubbe van de P , Maclean Y , Man de D , Matena A , Molenaar L , Mous J , Nijs H , Paassen van R , Quax J , Reijnierse A , Romme M , Rotte de M , Saltzherr B , Schaeybroeck G , Schardijn S , Schrauwen P , Sonnaville de F , Steenwinkel de L , Sturm T , Sutter I , Tchetverikov D , Tusschenbroek R , Veldman M , Vis A , Voordt van der H , Voorneveld M , Vroed de M , Walravens M , Walter A , Weel N , Werff van de A , Westeinde van het J , Wiele M , Willemse J , Wouter W , Zandbergen D , Zeben van H , Zwart  
Published: August 2021

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 &lt;12 months and &gt;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 (&lt;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.