Evolution from early to difficult-to-treat rheumatoid arthritis: incidence and risk factors in the ERA uclouvain Brussels cohort.

backgroundDespite an increasing number of targeted and biological disease-modifying anti-rheumatic drugs (ts or bDMARDs), a significant number of Rheumatoid Arthritis (RA) patients are refractory to multiple lines of treatments. The definition of Difficult-to-treat (D2T) RA patients has been proposed to harmonize research on this condition. While data on D2T in established RA are emerging, this is the first study to specifically address the evolution from early disease (ERA) to D2T-RA. To identify early clinical, laboratory, and radiographic predictors of progression from early rheumatoid arthritis to difficult-to-treat RA over a five-year follow-up.

methodsThis was a retrospective monocentric cohort study of DMARD-naïve ERA patients (symptom duration ≤ 12 months), enrolled between 2010 and 2019. Patients were followed for 5 years with data collection at baseline, 6, 12, 36, and 60 months. The primary outcome was the development of D2T-RA, defined according to EULAR 2021 criteria. Baseline analyzed variables included clinical features, serology, radiographic damage, disease activity scores, patient-reported outcomes (PROs) and demographic features. Associations between baseline variables and D2T status were evaluated using univariate and multivariate logistic regression analyses.

resultsWe included 391 ERA patients [M/F 109/282, median age 48.2 years IQR (21.26)]. After 5 years, forty-one patients (10.5%) matched the D2T definition. A higher baseline radiographic damage, seropositivity, and baseline disease activity characterized these patients. Only radiographic damage was confirmed as an independent factor for progression to D2T-RA in a multivariate analysis [OR = 2.38 CI (1.09-5.54); p = 0.03]. During the follow-up, disease activity was consistently higher in the D2T group. D2T patients were exposed to a higher dose of glucocorticoids and more commonly suffered from infections and osteoporosis.

conclusionsBaseline radiographic damage, seropositivity, and high disease activity represent the major risk factors for the evolution from ERA to D2T-RA. Disease activity indices were consistently higher in D2T patients all along the five-year follow-up. In addition, D2T patients received higher GC doses and more commonly developed disease and treatment-related comorbidities.