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Background: The EULAR response criteria, based on the 4-component DAS28 (4C-DAS28), are commonly used as the primary outcome in rheumatoid arthritis (RA) studies. However, a new 2-component DAS28 (2C-DAS28) has shown strong association with ultrasound assessed synovitis and radiographic joint progression 1. We hypothesize that response criteria based on this 2C-DAS28 would better reflect disease progression with respect to synovitis, and therefore better capture whether a given treatment is working to control joint inflammation for the patient or not. Objectives: To develop RA treatment response criteria based on the 2C-DAS28. Methods: This study aims to define thresholds of 2C-DAS28 remission, based on Boolean2.0 remission 2, and significant improvement, based on Clinical Disease Activity Index (CDAI) improvement criteria 3, using data from three different stages of RA progression. The proposed response criteria then consider patients as responders if they reach remission, or their 2C-DAS28 reduces significantly. The developed thresholds were tested in an independent cohort, based on their ability to discriminate patients with respect to imaging assessed synovitis, and results were compared to CDAI, and EULAR outcomes. Results: Complete data to calculate 2C-DAS28 at baseline and 3-month follow-up were available for three development cohorts representing early (N = 1047), established (N = 992), and late RA (N = 293). The validation data consisted of 68 and 55 patients with synovial thickness (ST), and power-doppler (PD) scores available at follow-up. The baseline 2C-DAS28 of early RA patients in Boolean2.0 remission (N = 42), was used to define the threshold for 2C-DAS28 remission (90th percentile: ≈ 1.8). 2C-DAS28 decreases of > 40/60/70% were found to maximize average kappa agreement with minor, moderate, and major CDAI decrease, across development cohorts (Figure 1). The 60% cutoff further maximized overall agreement and was therefore used to define the threshold for significant 2C-DAS28 improvement. In the validation data, 2C-DAS28 remission (follow-up 2C-DAS28 60%) show significantly reduced ST (p = 0.02) and PD scores (p = 0.007). By contrast, neither CDAI nor EULAR response criteria separated patients with respect to synovitis (Table 1). Conclusion: Compared to existing response criteria, the proposed criteria have shown stronger association with imaging detected synovitis. When used in conjunction with established disease activity criteria, this could aid clinical management of patients, as well as research to identify biomarkers of treatment efficacy. REFERENCES: 1 Hensor, Elizabeth M. A., et al. 'Validity of a Two-Component Imaging-Derived Disease Activity Score for Improved Assessment of Synovitis in Early Rheumatoid Arthritis'. Rheumatology, vol. 58, no. 8, Oxford University Press (OUP), 1 Mar. 2019, pp. 1400–09. 2 Studenic, Paul, et al. 'American College of Rheumatology/EULAR Remission Criteria for Rheumatoid Arthritis: 2022 Revision'. Annals of the Rheumatic Diseases, vol. 82, no. 1, BMJ, 24 Oct. 2022, pp. 74–80. 3 Aletaha, Daniel, et al. 'Definition of Treatment Response in Rheumatoid Arthritis Based on the Simplified and the Clinical Disease Activity Index'. Annals of the Rheumatic Diseases, vol. 71, no. 7, BMJ, 27 Mar. 2012, pp. 1190–96. Acknowledgements: This work was supported by the Medical Research Council (MRC) - grant code MR/N013751/1 Stadler, the Centre for Genetics and Genomics Versus Arthritis (CfGG), and the NIHR Cambridge Biomedical Research Centre (BRC). Anne Barton's work was additionally supported by the NIHR. Disclosure of Interests: Michael Stadler: None declared, Felice Rivellese: None declared, Darren Plant: None declared, Kimme Hyrich Speakers bureau: AbbVie, Grant/research support from: Pfizer, BMS, John Isaacs: None declared, Ann Morgan: None declared, Anthony G Wilson: None declared, Suzanne Verstappen: None declared, Myles Lewis: None declared, John Bowes: None declared, Costantino Pitzalis: None declared, Anne Barton Grant/research support from: BMS, Galapagos, Pfizer, and Scipher.
Stadler et al. (Sat,) studied this question.