Validity of a two-component imaging-derived disease activity score for improved assessment of synovitis in early rheumatoid arthritis

Author:

Hensor Elizabeth M A12ORCID,McKeigue Paul3,Ling Stephanie F4,Colombo Marco3,Barrett Jennifer H25,Nam Jackie L12,Freeston Jane12,Buch Maya H12,Spiliopoulou Athina36,Agakov Felix6,Kelly Stephen7,Lewis Myles J7ORCID,Verstappen Suzanne M M89,MacGregor Alexander J10ORCID,Viatte Sebastien4,Barton Anne49ORCID,Pitzalis Costantino7,Emery Paul12,Conaghan Philip G12,Morgan Ann W12

Affiliation:

1. Leeds Institute of Rheumatic and Musculoskeletal Medicine, School of Medicine, University of Leeds

2. NIHR Leeds Biomedical Research Centre, Leeds Teaching Hospitals NHS Trust, Leeds

3. Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Edinburgh

4. Arthritis Research UK Centre for Genetics and Genomics, Division of Musculoskeletal and Dermatological Sciences, The University of Manchester, Manchester

5. Leeds Institute of Cancer and Pathology, School of Medicine, University of Leeds, Leeds

6. Pharmatics Limited, Edinburgh

7. William Harvey Research Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London

8. Arthritis Research UK Centre for Epidemiology, Division of Musculoskeletal and Dermatological Sciences, The University of Manchester, Manchester

9. NIHR Manchester Biomedical Research Centre, Manchester University NHS Foundation Trust, Manchester

10. Norwich Medical School, University of East Anglia, Norwich, UK

Abstract

Abstract Objectives Imaging of joint inflammation provides a standard against which to derive an updated DAS for RA. Our objectives were to develop and validate a DAS based on reweighting the DAS28 components to maximize association with US-assessed synovitis. Methods Early RA patients from two observational cohorts (n = 434 and n = 117) and a clinical trial (n = 59) were assessed at intervals up to 104 weeks from baseline; all US scans were within 1 week of clinical exam. There were 899, 163 and 183 visits in each cohort. Associations of combined US grey scale and power Doppler scores (GSPD) with 28 tender joint count and 28 swollen joint count (SJC28), CRP, ESR and general health visual analogue scale were examined in linear mixed model regressions. Cross-validation evaluated model predictive ability. Coefficients learned from training data defined a re-weighted DAS28 that was validated against radiographic progression in independent data (3037 observations; 717 patients). Results Of the conventional DAS28 components only SJC28 and CRP were associated with GSPD in all three development cohorts. A two-component model including SJC28 and CRP outperformed a four-component model (R2 = 0.235, 0.392, 0.380 vs 0.232, 0.380, 0.375, respectively). The re-weighted two-component DAS28CRP outperformed conventional DAS28 definitions in predicting GSPD (Δtest log-likelihood <−2.6, P < 0.01), Larsen score and presence of erosions. Conclusion A score based on SJC28 and CRP alone demonstrated stronger associations with synovitis and radiographic progression than the original DAS28 and should be considered in research on pathophysiological manifestations of early RA. Implications for clinical management of RA remain to be established.

Funder

Medical Research Council (MRC) and Arthritis Research UK

their joint funding of Maximizing Therapeutic Utility in Rheumatoid Arthritis

Publisher

Oxford University Press (OUP)

Subject

Pharmacology (medical),Rheumatology

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