Best of 2022: Undifferentiated Arthritis Does Not Follow an RA Course Save

Editor's note: this article originally appeared March 7, 2022, and is being shared again as a Best of 2022. Enjoy!

Undifferentiated arthritis (UA) is common in medical practice and many advocate early use of DMARDs; yet a recent study shows that despite DMARD use, UA patients do not fair well with this approach.

While there are criteria for UA, it is largely a diagnosis of exclusion. Moreover, there are few well controlled trials on DMARD efficacy in UA are absent.

For this study UA was defined, as clinical arthritis (joint swelling at physical examination), not fulfilling the 1987, nor 2010, RA-criteria. Patient from the  Leiden Early Arthritis Clinic (EAC) were enrolled during 5 inclusion periods: 1993–1997, 1998–2005, 2006–2010, 2011–2014 and 2015–2019. DMARD use was correlated with clinical variables and outcomes. 

This study included 1132 UA patients, that was autoantibody negative, with a median swollen joint count of 2, tender joint count of 3 and HAQ score of 0.6; this profile did not change with time.

From 1993–1997 to 2015–2019, DMARD use increased from 17% to 52%, with methotrexate being more commonly used. With time, the DAS28-CRP improved from 2011 onwards (−0.18 to −0.25 DAS units; P < 0.05), but disability scores did not significantly improve and disease free status at 10 years remained stable at 58%, 57% and 61% for 1993–1997, 1998–2005 and 2006–2010, respectively (P = 0.77).

Also the percentage of UA evolving into RA did not decrease with treatment and era (14%, 21%, 26%, 18% and 27%, respectively).

Increased DMARD use in this large UA cohort had modest effects on disease activity scores, no no effect on physical functioning and long-term outcomes.  One could argue that this approach to overtreatng contemporary UA without substantial benefit calls for better stratification methods and more tailored approaches to UA patients.

Another recent report in Annals of Rheumatic Disease looked at mortality outcomes in RA versus UA.  It is well known that RA contributes to excess mortality risk A, excess mortality after 10 years of disease in both anticitrullinated protein antibody (ACPA)-negative and ACPA-positive RA; presumably from long-term inflammation.  This analysis looked at 860 conventional UA patients and 561 contemporary UA-patients (also from the Leiden EAC) who were followed for 17 years. Unlike RA mortality (increased with time), mortality in these UA cohorts was not increased (SMR 1.11; 0.96 to 1.27 and SMR 1.05; 0.87 to 1.26, respectively) and was not changed by DMARD use or autoantibody stratification. 

Both studies underscore the atypia underlying a "UA" diagnosis and that new strategies are needed to yield better outcomes for such patients.