{
  "abstract": "Objectives Unresponsive outcome measures for lupus arthritis contribute to misleading results in SLE trials. We aimed to optimise assessment of lupus arthritis through the development of a novel disease activity measure, derived against ultrasound-proven synovitis and incorporating participant experience.Methods The LAMDA was derived in the baseline data from the USEFUL study of 133 participants receiving glucocorticoid therapy for lupus arthritis (PMID: 33792659). Penalised multiple quantile (median) regression of total grey scale (GS) and power Doppler (PD) score from bilateral hand and wrist joints on ACR rheumatoid arthritis core set variables (68 tender and 66 swollen joint counts [TJC68, SJC66], HAQ-DI, erythrocyte sedimentation rate [ESR], and visual analogue scales [VAS] for participant’s MSK pain and disease activity, physician’s MSK disease activity), and early morning stiffness severity VAS derived the score.Convergent construct validity, known groups validity, longitudinal construct validity and responsiveness were assessed. Thresholds of meaning for trial entry (derived against <2/>=2 joints with GS>=2 and/or PD>=1), minimal clinically important improvement (derived for relative change in LAMDA at week 6 against </>= moderate participant-reported improvement in MSK symptoms), and participant acceptable symptom state were established using receiver operator characteristic curve analysis. Remission was provisionally defined using a Boolean approach (SJC28<=1, ESR normalized, VASs<=20mm).Results The model retained four variables SJC66, ESR and VASs for physician MSK disease activity and participant MSK pain. High intra-class correlation supported substituting SJC28 for SJC66. LAMDA demonstrated good construct validity, correlating with conventional disease activity measures, ultrasound findings and participant-reported outcomes better than SJC ( figure 1A and C). LAMDA yielded a larger treatment effect than SJC28 (Wilcoxon signed rank test effect size 0.40 vs 0.20) and change in LAMDA showed a stronger correlation with US and participant reported change than change in SJC (figure 1B). Provisional thresholds of meaning (figure 1D) showed logical consistency with participant characteristics (figure 1E).Abstract S13:02 Figure 1A) Spearman correlation of LAMDA28/SJC28 with baseline ultrasound (US) and patient-reported outcomes. B) Correlation of change in LAMDA28/SJ C28 with change in US activity and participant reported change between baseline and week 6. C) Construct validity: comparison of LAMDA28/SJC28 between known groups. D) Characteristics (95% Cl) of proposed LAMDA thresholds for trial entry, MCII and PASS. E) Characteristics of participants above/below proposed thresholds for trial entry, PASS and remissionConclusions LAMDA is a novel US-derived clinical disease activity measure to improve the assessment of lupus arthritis. Further validation is underway in multinational RCTs. LAMDA was selected as the arthritis domain of the TRM-SLE project to define a new primary endpoint for SLE clinical trials.",
  "authors": [
    {
      "affiliations": [
        "University of Leeds, Leeds Institute for Rheumatic and Musculoskeletal Medicine, Leeds, UK"
      ],
      "name": "Samuel Wood"
    },
    {
      "affiliations": [
        "University of Leeds, Leeds Institute for Rheumatic and Musculoskeletal Medicine, Leeds, UK"
      ],
      "name": "Khaled Mahmoud"
    },
    {
      "affiliations": [
        "University of Leeds, Leeds Institute for Rheumatic and Musculoskeletal Medicine, Leeds, UK",
        "Leeds Teaching Hospital NHS Trust, NIHR Leeds Biomedical Research Centre, Leeds, UK"
      ],
      "name": "Philip Conaghan"
    },
    {
      "affiliations": [
        "University of Leeds, Leeds Institute for Rheumatic and Musculoskeletal Medicine, Leeds, UK"
      ],
      "name": "Elizabeth Hensor"
    },
    {
      "affiliations": [
        "University of Leeds, Leeds Institute for Rheumatic and Musculoskeletal Medicine, Leeds, UK"
      ],
      "name": "Edward Vital"
    }
  ],
  "title": "S13:02 Advancing arthritis assessment in SLE clinical trials: derivation, validation and proposed thresholds of the lupus arthritis and musculoskeletal disease activity (LAMDA) instrument",
  "uid": "a09daa2f-5498-52a1-8b51-ca5259578deb"
}