POS0485 TRAJECTORY CLUSTERS OF RADIOGRAPHIC PROGRESSION IN RHEUMATOID ARTHRITIS PATIENTS: ASSOCIATIONS WITH CLINICAL VARIABLES
Authors: S. Blüml, A. Platzer, F. Alasti, D. Aletaha, J. S. Smolen, H. Radner
Journal: Annals of the Rheumatic Diseases (2021)

Background: Joint damage is a defining feature of rheumatoid arthritis (RA), a major driver of functional impairment and of reduction of quality of life. Many factors are associated with damage accrual however, the course of structural damage of individual patients over time and factors associated with such trajectories have not been investigated. Objectives: Identification of trajectories of radiographic damage in RA by clustering patients according to the shape of their curve of Sharp-van der Heijde scores (SHS) over time. Developing models to predict their progression cluster from baseline characteristics. Methods: Patient-level data over a two-year period from 5 large randomized controlled trials on TNF-inhibitors in RA (ERA, PREMIER, TEMPO, GO-BEFORE and GO-FORWARD) were used. SHSs were clustered in a shape-respecting manner to identify distinct clusters of radiographic progression. Characteristics of patients within different progression clusters were compared at baseline and over time. Logistic regression models were developed to predict trajectory of radiographic progression using information at baseline. Results: In total 1887 patients with 7738 x-rays were used for cluster analyses. We identified 4 distinct clusters with characteristic shapes of radiographic progression: one with a stable SHS over the whole 2-year period (C0/lowChange; 86%); one with relentless progression (C1/rise; 5.8%); one with decreasing SHS (C2/improvement; 6.9%); and one going up and down (C3/bothWays; 1.4%) of the SHS. Robustness of clusters and shapes of progression over time were confirmed using different clustering methods and cut-offs to define radiographic progression (Figure 1). Regression models identified disease duration, baseline CRP and SHS and treatment status as predictors for cluster assignment (Table 1), showing good performance (PCC 87.5%; Nagelkerke r 2 0.36 ). Conclusion: We were able to identify 4 different clusters of radiographic progression over time in patients with RA, most remarkably one with relentless progression and another one with amelioration of joint damage over time, suggesting the existence of distinct patterns of joint damage accrual in RA. The nature of the identified trajectories is mostly explained by inflammatory load, disease duration and especially type of treatment. Figure 1. Representations of the major three clusters of radiologic progression curves. (A) shows the curves of all patients with a SHS-range &gt;= 10, colored by their cluster. Values between visits were linearly interpolated. Big dotted line is the median of particular cluster, thinner lines represent single patient values. Cluster C0 /lowChange are patients without enough variation in SHS to be seen as a curve, therefor not shown in the diagrams. Table 1. Simple logistic regression models to predict assignment to clusters of radiologic progression using information at baseline. Variables entered but not selected by a stepwise approach were: rheumatoid factor, age, gender, tender joint count ; c0/low change vs: C1/rise Cluster C2/improve Cluster parameters OR 95%CI OR 95%CI X-ray Score 1.02 1.01-1.03 1.03 1.02-1.03 CRP (mg/dl) 1.12 1.07-1.16 0.98 0.90-1.07 Duration (years) 0.87 0.80-0.95 1.09 1.05-1.12 Treatment Combination REF REF REF REF csDMARD 4.98 2.88-8.63 0.05 0.01-0.23 bDMARD Mono 2.28 1.29-4.04 0.64 0.38-1.08 Disclosure of Interests: Stephan Blüml Speakers bureau: Novartis, MSD, Abvie, Pfizer, Consultant of: MSD, Lilly, Novartis, Alexander Platzer: None declared, Farideh Alasti: None declared, Daniel Aletaha Speakers bureau: Abbvie, Amgen, Lilly, Merck, Novartis, Pfizer, Roche, Sandoz, Consultant of: Abbvie, Amgen, Lilly, Merck, Novartis, Pfizer, Roche, Sandoz, Grant/research support from: Abbvie, Amgen, Lilly, Novartis, Roche, SoBi, Sanofi, Josef S. Smolen Speakers bureau: AbbVie, Amgen, AstraZeneca, Astro, Bristol-Myers Squibb, Celgene, Celltrion, Chugai, Gilead, ILTOO Pharma, Janssen, Lilly, Merck Sharp &amp; Dohme, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi, and UCB., Consultant of: AbbVie, Amgen, AstraZeneca, Astro, Bristol-Myers Squibb, Celgene, Celltrion, Chugai, Gilead, ILTOO Pharma, Janssen, Lilly, Merck Sharp &amp; Dohme, Novartis-Sandoz, Pfizer, Roche, Samsung, Sanofi, and UCB., Grant/research support from: Dr Smolen received grants to his institution from Abbvie, AstraZeneca, Janssen, Lilly, Merck Sharpe &amp; Dohme, Pfizer, and Roche, Helga Radner: None declared