Background
Outcome measures for lupus arthritis that are not sensitive to change might contribute to misleading results in systemic lupus erythematosus (SLE) trials. We aimed to optimise lupus arthritis assessment by developing a novel composite disease activity measure, derived against ultrasound synovitis and incorporating participant-reported outcomes.
Methods
In this cohort study we derived the Lupus Arthritis and Musculoskeletal Disease Activity (LAMDA) score from baseline data in a prospective, longitudinal, multicentre study (USEFUL) of participants with SLE receiving intramuscular glucocorticoid therapy for lupus arthritis recruited from seven hospitals in England. Penalised multiple quantile (median) regression of total combined grey scale and power Doppler scores from bilateral hand and wrist joint ultrasounds on inflammatory arthritis core set variables defined by the American College of Rheumatology (tender joint count in 68 joints, swollen joint count in 66 joints, Health Assessment Questionnaire Disability Index, erythrocyte sedimentation rate [ESR], and visual analogue scales [VAS] for patient's musculoskeletal pain and disease activity and physician's musculoskeletal disease activity), and early morning stiffness severity VAS was used to derive the score. We assessed convergent construct validity, known groups validity, and responsiveness. We established thresholds of meaning for trial entry, minimal disease activity, participant acceptable symptom state, and minimal clinically important improvement using receiver operating characteristic curve analysis. A separate external validation cohort was recruited from Leeds Teaching Hospitals NHS Trust, clinical outcomes and treatment intention were collected by clinicians who were not involved in the USEFUL study. The construct validity of LAMDA within this external validation cohort was assessed, including discrimination of treatment intention and participant acceptable symptom state. People with lived experience of SLE were involved in the design and delivery of both the USEFUL study and the present study.
Findings
133 participants recruited between Oct 20, 2016, and Dec 20, 2018, were included from the USEFUL study; mean age was 47·0 years (IQR 35·0–55·0), 126 (95%) were female, seven (5%) were male, and 82 (62%) were White. The model retained four variables in the LAMDA score: swollen joint count in 66 joints, ESR, VAS for physician musculoskeletal disease activity, and participant musculoskeletal pain. High intraclass correlation (>0·99) supported directly substituting swollen joint count in 28 joints for swollen joint count in 66 joints to improve feasibility. LAMDA showed good construct validity, correlating with conventional disease activity measures, ultrasound findings, and patient-reported outcomes. LAMDA was responsive, yielding a medium-to-large early treatment effect following glucocorticoid therapy (effect size 0·40, p<0·0001). Provisional thresholds of meaning showed good logical consistency with participant characteristics and patient-reported change in musculoskeletal pain. The external validation cohort included 44 participants, recruited between Nov 15, 2017, and July 23, 2020; median age was 48·5 years (IQR 39·0–56·0), 38 (86%) were female, six (14%) were male, and 32 (73%) were White. The findings from the external validation cohort were supportive of the initial findings. LAMDA was correlated with multiple participant reported outcome measures and the proposed thresholds of meaning outperformed swollen joint counts alone in discriminating treatment intention and participant acceptable symptom state.
Interpretation
LAMDA is a novel ultrasound-derived clinical disease activity measure that should improve the assessment of lupus arthritis in clinical trials and real-world practice. Further validation is underway in large multinational randomised controlled trials.
Funding
None
CORE (COnnecting REpositories)
CORE (COnnecting REpositories)