Objectives
International guidelines stress timely DMARD-initiation in early-arthritis, also when classification-criteria are not yet fulfilled. Consequently, undifferentiated arthritis (UA)-patients may be increasingly treated with DMARDs. Since UA is a diagnosis per exclusionem, the introduction of the 2010-classification-criteria presumably decreased the UA-population as former UA-patients became regarded as RA. The contemporary definition of UA has therefore become: not fulfilling the 1987- nor 2010-criteria. Importantly, placebo-controlled trials on DMARD-efficacy in contemporary UA are absent. We aimed to study whether enhanced treatment-strategies across 25-years improved outcomes in contemporary UA, whereby inclusion-period was an instrumental variable for DMARD-treatment.
Methods
UA was defined, retrospectively, as clinical arthritis (joint-swelling at physical-examination) neither fulfilling the 1987 nor 2010-RA-criteria, nor any other clinical diagnosis. In total, 1132 UA-patients, consecutively included in the Leiden-EAC between 1993–2019, were studied, divided into 5 inclusion-periods; 1993–1997, 1998–2005, 2006–2010, 2011–2014, 2015–2019. Frequency of DMARD-initiation was compared across the inclusion-periods, as were the following outcomes: DAS28CRP and disability (HAQ-DI) during follow-up, prevalence of DMARD-free-status within 10-years (DFS; spontaneous remission or sustained remission after DMARD-stop) and progression to RA (according 1987/2010-criteria).
Results
The contemporary UA-population is mainly autoantibody-negative, with median SJC = 2, TJC = 3 and HAQ = 0.6. These characteristics were similar across the inclusion-periods. DMARD-treatment increased from 17% (1993–1997) up-to 52% (2015–2019), methotrexate became more common. DAS28CRP during follow-up improved from 2011 onwards (-0.18,-0.25DAS-units/p< 0.05). Disability-scores during follow-up did not significantly improve. DFS-prevalence also remained similar: 58%, 57%, 61% (1993–1997/1998–2005/2006–2010; p= 0.77). Likewise, the percentages RA-development did not decrease (14%/21%/26%/18%/27%).
Conclusion
Although intensified DMARD-treatment slightly improved disease-activity-scores, physical-functioning and long-term outcomes did not improve. This suggests overtreatment in the contemporary UA-population and underlines the importance to develop stratification-methods suitable for this population.