THU0101 IMPACT OF TREATMENTS ON RADIOGRAPHIC PROGRESSION OVER THE FIRST 10 YEARS OF DISEASE IN EARLY RHEUMATOID ARTHRITIS: RESULTS FROM THE ESPOIR COHORT
Authors: J. Kedra, D. Hajage, A. Lafourcade, B. Combe, M. Dougados, B. Fautrel
Journal: Annals of the Rheumatic Diseases (2020)

Background: Long-term observational studies on the prediction of structural damage progression (SDP) in rheumatoid arthritis (RA) have mostly considered patients baseline characteristics and have rarely evaluated the specific impact of treatments in real world settings. Objectives: To assess the impact of treatments exposure on the 10-year radiographic progression in early rheumatoid arthritis (RA). Methods: The 310 patients of the ESPOIR cohort fulfilling ACR/EULAR 2010 criteria at baseline and having complete radiographic data at baseline and 10 years were considered in the present study. SDP was defined at 10 years as a significant increase of the Sharp/van der Heijde score, i.e., superior to the Smallest Detectable Change of 11.5 at 10 years. Three RA treatments were considered: glucocorticoids (GC), conventional synthetic and biologic Disease-Modifying Anti-Rheumatic Drugs (csDMARDs and bDMARDs), which posologies were standardized by the mean of dose quotients (DoseQ). Drug exposure was modelled with Weighted Cumulative Exposure (WCE) variables, considering the intensity of drug exposure defined as a weighted function of past doses, and was incorporated into a logistic regression model that also included baseline clinical, biological and radiological characteristics. The predictive performance of this WCE model was compared to models considering on the one hand only baseline characteristics (BSL model) and on the other, baseline characteristics and binary treatments exposure - in other terms, “ever exposed, yes or no” (BIT model). Results: Overall, SDP at 10 years occurred in 85 (27.4%) patients. GC exposure was significantly associated with SDP in univariate analysis only, and therefore was not included in the final WCE model. In the final WCE model, the joint exposure to 1 DoseQ of csDMARD and 1 DoseQ of bDMARD during the 10-year follow-up was associated with a significant protective effect on SDP compared to patients receiving no treatment: OR=0.04 (95% CI: 0.002-0.72). Early csDMARD initiation was associated with a significantly lower risk of SDP compared to later initiation (Table 1). Table 1. odd ratios for the association of patterns of drug regimen with 10-year radiographic progression Exposure tested Reference OR (95%CI) Treatments intakes during the last 10 years csDMARD &amp; bDMARD for last 10 years No treatment for last 10 years 0.04 (0.002-0.72) Testing the interest of an early initiation of csDMARDs (not combined with bDMARD) csDMARD for last 10 years csDMARD after month 3 0.79 (0.65-0.96) csDMARD after month 6 0.41 (0.19-0.86) csDMARD after year 1 0.13 (0.02-0.80) Testing the interest of an early initiation of bDMARDs (in association with csDMARD) bDMARD after month 3 No treatment for last 10 years 0.04 (0.002-0.72) bDMARD after month 6 0.04 (0.002-0.72) bDMARD after year 1 0.04 (0.002-0.72) bDMARD after year 2 0.04 (0.003-0.73) bDMARD after year 3 0.05 (0.03-0.81) Initiation of a bDMARD between the 3rd month and 3rd year of follow-up in combination with a csDMARD was significantly associated with a lower risk of SDP compared to no bDMARD treatment (Table 1). The final WCE model was better at predicting SDP at 10 years compared to the BSL and BIT models, with AUC=0.92 (95% CI: 0.89-0.95) (Figure 1). Figure 1. ROC curves of BSL model (A), BIT model (B) and WCE combined model (C) for 10-year radiographic progression Conclusion: CsDMARDs and bDMARDs have a protective effect on radiographic progression at 10 years in RA patients. This study has shown the value of considering drug exposure in the study of RA prognosis, and modeling this exposure using WCE variables. Disclosure of Interests: Joanna KEDRA: None declared, David Hajage: None declared, Alexandre Lafourcade: None declared, Bernard Combe Grant/research support from: Novartis, Pfizer, Roche-Chugai, Consultant of: AbbVie; Gilead Sciences, Inc.; Janssen; Eli Lilly and Company; Pfizer; Roche-Chugai; Sanofi, Speakers bureau: Bristol-Myers Squibb; Gilead Sciences, Inc.; Eli Lilly and Company; Merck Sharp &amp; Dohme; Pfizer; Roche-Chugai; UCB, Maxime Dougados Grant/research support from: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Consultant of: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Speakers bureau: AbbVie, Eli Lilly, Merck, Novartis, Pfizer and UCB Pharma, Bruno Fautrel Grant/research support from: AbbVie, Lilly, MSD, Pfizer, Consultant of: AbbVie, Biogen, BMS, Boehringer Ingelheim, Celgene, Lilly, Janssen, Medac MSD France, Nordic Pharma, Novartis, Pfizer, Roche, Sanofi Aventis, SOBI and UCB