BIOLOGIC DISEASE-MODIFYING ANTIRHEUMATIC DRUGS PRESCRIPTION over TIME in A COHORT of EARLY RHEUMATOID ARTHRITIS PATIENTS

ABSTRACT

Background: According to 2019 updated EULAR recommendations, therapy of Early Rheumatoid Arthritis (ERA) with biological disease-modifying antirheu-matic drugs(bDMARDs) is adviced in presence of poor prognostic factors,I.e. persistently moderate/high disease activity, high acute phase reactants, high swollen joint count, autoantibody positivity, presence of early erosions, failure of two/more conventional synthetic DMARD. Objectives: To evaluate over time prevalence of bDMARD therapy and factors associated to rapid initiation in our EA Clinic (EAC), comparing two different periods from 2004 to 2012 and from 2012 to 2020. The last two years were not considered because of the adverse influence of COVID19 pandemia on early access to EAC and on timely scheduled visits. Methods: A total of 281 ERA patients with less than 12 months of disease duration (53.9 years mean age, 75% female, 77% seropositive), followed according to the treat-to-target (T2T) strategy, were enrolled in the study. At baseline, and every three months, the ACR/EULAR core data set variables were recorded. At baseline and every year, hand and foot radiographs were examined according to modifed Total Sharp score (mTSS). At each visit, clinical improvement and remission were evaluated according to EULAR criteria. The achievement of Comprehensive Disease Control (CDC) (28-joint Disease Activity Score using C reactive protein <2.6, Health Assessment Questionnaire <0.5 and change from baseline in mTSS ≤0.5) was assessed every year. Results: We examined 164 patients from 2004 to 2012 and 117 subjects from 2012 to 2020. In the frst group 72 patients (43.9%) initiated bDMARDs during the 8-year FU, with a mean delay of 41.8 months. In the second group 37 patients (31.6%) started biotechnological drugs over time, with a mean delay of 50.4 months. Analyzing the period from 2004 to 2012, ERA patients starting bDMARDs were younger (p<0.0001), had longer disease duration (p=0.02) and higher body mass index (BMI) (p=0.01) compared to subjects not undergoing to biological therapy. Moreover, ERA patients in bDMARDs were in higher percentage anti-citrullinated peptide antibody (ACPA) positive (80.6%) and reached to a lesser extent CDC at 12months of FU (26.1%) compared to patients that didn't initiate bDMARDs (60.9% ACPA positive, p=0.01;63% achieving CDC, p<0.0001, respectively). Examining the period from 2012 to 2020, bDMARD-treated ERA patients were younger (p=0.06),in higher percentage ACPA positive (81.1%) and erosive at baseline (35.1%) compared to patients that didn't initiate bDMARDs (64% ACPA positive, p=0.02;17.5% erosive, p=0.04, respectively). As previously, patients in bDMARD reached to a lesser extent CDC at 12 month of FU (35.1%) compared to subjects not undergoing to biological therapy (55% achieving CDC, p=0.05). On multivariate analysis, ACPA positivity was associated with initiation of bDMARD in both patient groups (p=0.02), whereas older age at onset and reaching CDC at 12 month were inversely associated (p=0.001;p<0.0001, respectively). Conclusion: Despite the widest choice of bDMARDs currently available in the last 8 years, we did not observe an increase in the prescription of these drugs from 2012 to 2020. As in other ERA cohorts, bDMARD initiation is associated to poor prognostic factors, in particular ACPA positivity, presence of erosions at baseline and not achieving CDC at 12 months of FU. In the last 8 years, the decreased influence of disease duration at onset and of BMI could be a consequence of the improvement in strategies of early referral and control of modifable risk factors.