FRI0043 JOINT SPACE NARROWING PRECEDES EROSIVE RADIOGRAPHIC DAMAGE IN PATIENTS WITH RHEUMATOID ARTHRITIS
Authors: A. Kerschbaumer, F. Alasti, G. Supp, J. S. Smolen, D. Aletaha
Journal: Annals of the Rheumatic Diseases (2020)

Background: Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized through symmetric polyarthritis leading to joint destruction over time in many patients. Radiographic damage is an important outcome in RA clinical trials, most commonly assessed by conventional radiographs and quantified/reported by the modified total Sharp van der Heijde Score (mTSS). The mTSS is assessing erosive (ERO) changes as well as joint space narrowing (JSN; reflecting cartilage wasting) in the small joints of the hands and feet. While erosions are the hallmarks of RA, loss of cartilage has been reported to be highly relevant for functional limitations in RA. The sequence of occurrence of these events is not completely understood. Objectives: To investigate the time to radiographic progression and assess potential differences between time-to-JSN progression and time-to-ERO progression. Methods: Radiographs of RA patients from a large prospective clinical routine cohort were scored using the mTSS by one experienced reader (G.S.) unaware of the aim of this project. Time-to-JSN and time-to-ERO was estimated using survival analyses utilizing the Kaplan-Meier estimator. In additional analyses, patients were stratified based on JSN and/or ERO damage at baseline. Further, potential predictors (demographics, csDMARD/bDMARD treatment/combination therapy) of time-to-ERO and time-to-JSN were evaluated using Cox-regression techniques. All statistical analyses were conducted using SAS v9.4 (Cary, New York, USA). Results: We assessed 798 patients longitudinally for radiographic progression. JSN occurred significantly earlier than erosions (p&lt;0.001, Figure 1). After stratification for baseline damage (Figure 2), these differences remained significant with a shorter time-to-JSN in patients without any baseline ERO or JSN (n=44, p=0.008), patients with JSN but no ERO at baseline (n=200, p&lt;0.001), and patients with baseline ERO and JSN (n=536, p&lt;0.001). Only in the small group of patients with isolated erosions (without JSN) at baseline there was no difference in time-to-progression of ERO vs. JSN (n=18, p=0.241). Overall, shorter time to progression of ERO was significantly predicted by positivity for rheumatoid factor or anti-citrullinated peptide antibodies (CCP; p&lt;0.003), as well as by erosions at baseline (p&lt;0.001) in Cox regression. In contrast, seropositivity for neither RF nor CCP was associated with shorter time to JSN progression (p=0.226); however, baseline concomitant JSN and ERO damage did show to be a significant predictor (p&lt;0.001). Figure 1. Time to joint space narrowing and time to erosive damage (n=798). Figure 2. Time to JSN/ERO stratified by presence or absence of ERO/JSN at baseline. Conclusion: We identified a significantly shorter time to progression of JSN compared to ERO in this longitudinal cohort of RA patients. JSN remains an important radiographic outcome, as it is strongly associated with impairment of physical function. This calls for a stronger focus on cartilage damage in RA, and a stronger consideration of JSN in routine evaluation of RA radiographs in clinical practice. Disclosure of Interests: Andreas Kerschbaumer Paid instructor for: Celgene, Speakers bureau: Andreas Kerschbaumer has received lecture fees from Bristol-Myers Squibb, Gilead, Merck Sharp and Dohme and Pfizer., Farideh Alasti: None declared, Gabriela Supp: None declared, Josef S. Smolen Grant/research support from: AbbVie, Eli Lilly, Janssen, Merck Sharp &amp; Dohme, Pfizer, Roche – grant/research support, Consultant of: AbbVie, Amgen Inc., AstraZeneca, Astro, Celgene Corporation, Celtrion, Eli Lilly, Glaxo, ILTOO, Janssen, Medimmune, Merck Sharp &amp; Dohme, Novartis, Pfizer, Roche, Samsung, Sanofi, UCB – consultant, Speakers bureau: AbbVie, Amgen Inc., AstraZeneca, Astro, Celgene Corporation, Celtrion, Eli Lilly, Glaxo, ILTOO, Janssen, Medimmune, Merck Sharp &amp; Dohme, Novartis, Pfizer, Roche, Samsung, Sanofi, UCB – speaker, Daniel Aletaha Grant/research support from: AbbVie, Novartis, Roche, Consultant of: AbbVie, Amgen, Celgene, Lilly, Medac, Merck, Novartis, Pfizer, Roche, Sandoz, Sanofi Genzyme, Speakers bureau: AbbVie, Celgene, Lilly, Merck, Novartis, Pfizer, Sanofi Genzyme, UCB