Ultrasound to identify systemic lupus erythematosus patients with musculoskeletal symptoms who respond best to therapy: the US Evaluation For mUsculoskeletal Lupus longitudinal multicentre study

Abstract

Objectives: To determine whether SLE patients with inflammatory joint symptoms and US synovitis/tenosyovitis achieve better clinical responses to glucocorticoids compared with patients with normal scans. Secondary objectives included identification of clinical features predicting US synovitis/tenosynovitis.

Methods: In a longitudinal multicentre study, SLE patients with physician-diagnosed inflammatory joint pain received intramuscular methylprednisolone 120 mg once. Clinical assessments, patient-reported outcomes and bilateral hand/wrist USs were collected at 0, 2 and 6 weeks. The primary outcome (determined via internal pilot) was the early morning stiffness visual analogue scale (EMS-VAS) at 2 weeks, adjusted for baseline, comparing patients with positive (greyscale ≥2 and/or power Doppler ≥1) and negative US. Post hoc analyses excluded FM.

Results: Of 133 patients, 78 had a positive US. Only 53 (68%) of these had one or more swollen joint. Of 66 patients with one or more swollen joint, 20% had a negative US. A positive US was associated with joint swelling, symmetrical small joint distribution and serology. The primary endpoint was not met: in the full analysis set (N = 133) there was no difference in baseline-adjusted EMS-VAS at week 2 [-7.7 mm (95% CI -19.0, 3.5); P = 0.178]. After excluding 32 patients with FM, response was significantly better in patients with a positive US at baseline [baseline-adjusted EMS-VAS at 2 weeks -12.1 mm (95% CI -22.2, -0.1); P = 0.049]. This difference was greater when adjusted for treatment [-12.8 mm (95% CI -22, -3); P = 0.007]. BILAG and SLEDAI responses were higher in US-positive patients.

Conclusion: In SLE patients without FM, those with a positive US had a better clinical response to therapy. Imaging-detected synovitis/tenosynovitis may be considered to decide on therapy and enrich clinical trials.

Keywords: biomarkers; clinical trials and methods; outcome measures; systemic lupus erythematosus; ultrasound.

Fig. 1

Study schematic All patients followed the same treatment and assessment protocol. Clinical data shown from the first 70 patients was used to decide the primary clinical response variable and thereby calculate statistical power. Additional patients were then recruited to this target. US data was not unblinded until all patients were recruited.

Fig. 2

Primary endpoint: clinical response according to baseline US (A) Primary efficacy variable (EMS-VAS at week 2) according to baseline US status. Vertical dotted line indicates degree of improvement in patients with active US at baseline was the same as patients with inactive US at baseline. Values to the left of this line show patients with active US at baseline had better response to therapy. Primary analysis model was adjusted for the baseline EMS-VAS only. Sensitivity analysis was also adjusted for use of NSAIDs, prednisolone and immunosuppressants. Analyses were also repeated for per-protocol population and exclusion of patients with FM. (B–E) Improvement in musculoskeletal components of the BILAG and SLEDAI according to baseline US status. (B) Percentage of patients with improvement in the musculoskeletal component of the BILAG. Improvement was defined as a reduction by at least one grade (i.e. A to B, B to C or C to D). (C) Same analyses excluding patients with FM. (D) Percentage of patients with improvement in the musculoskeletal items on the SLEDAI (arthritis and myositis, although no patient in this study was scored for myositis). Improvement was therefore defined as resolution of arthritis (reduction from 4 points to 0 points). (E) Same analysis excluding patients with FM.

Fig. 3

Change in the three most relevant domains of LupusQoL according to baseline US status The vertical dotted line indicates that the degree of improvement in patients with active US at baseline was the same as for patients with inactive US at baseline. Values to the left of this line indicate a better response in patients with active US at baseline. The primary analysis model was adjusted for baseline values. The sensitivity analysis was also adjusted for use of NSAIDs, prednisolone and immunosuppressants. These analyses were repeated excluding patients with FM.