Background/Purpose: Clinical trial evaluations in SLE have been problematic, in part due to glossary-based outcome measures that provide imperfect thresholds for grading flares or improvement. Visual analogue scales (VAS) allow refined scaling of change in disease severity, grounded in real world clinical observation, but have been inconsistent in practice when used over time or by different raters. The SELENA SLEDAI Physician’s Global Assessment (SSPGA) is a VAS with severity anchors and a simple but specific protocol for scoring designed to improve inter-and intra-rater consistency. The Rapid Evaluation of Activity in Lupus (LFA-REAL^TM) extends the SS PGA structure by providing separate scales for each active symptom, supporting evaluation of patient progress in individual symptoms, organs, or total disease activity. We compared performance of SS PGA and LFA-REAL^TM to accepted SLE trial outcome measures during an ongoing trial in SLE.

Methods: Disease activity (SLEDAI, BILAG 2004, SS PGA and LFA-REAL^TM) was evaluated at consecutive monthly visits in an investigator-initiated, double-blind, placebo controlled trial of abatacept (trial results pending). Validation of total scores and change in SSPGA and REAL vs SLEDAI and BILAG were examined by Spearman Correlation. ROC curve analysis (SAS) was applied to compare changes in SSPGA and LFA-REAL^TM to frequently used dichotomous SLE trial endpoints, SRI-4 and BICLA.

Results: 50 patients [47 female, mean age (SD) 45 (11.6) years] were assessed at 528 visits. Changes in disease activity compared to baseline were examined in 478 visit pairs. Total SSPGA and REAL scores strongly correlated to each other (r=0.936), as well as to total SLEDAI and BILAG [SS PGA: r= 0.742 (SLEDAI), r=0.776 (BILAG). REAL: r=0.778 (SLEDAI), r=0.813 (BILAG); all p<0.0001]. Changes in SS PGA and LFA-REAL^TM at each visit compared to screening correlated to each other (r= 0.857) as well as to changes in SLEDAI and BILAG [Delta SS PGA: r=0.678 (Delta SLEDAI), r= 0.624 (Delta BILAG); Delta LFA-REAL^TM: r=0.686 (Delta SLEDAI), and 0.700 (Delta BILAG); all p<0.0001]. Changes in SS PGA and LFA-REAL^TM were very strongly related to the dichotomous SRI-4 and BICLA endpoints by ROC analysis (p<0.0001 for all) (Table 1). Mean (95% CI) improvement in SS PGA reflecting SRI-4 was 37.3mm (35.4 to 39.3mm) and for LFA-REAL^TM 52mm (48.9 to 55.1mm). Unlike SS PGA, LFA-REAL^TM could be correlated to BILAG individual organ scores with musculoskeletal scores r=0.842 and mucocutaneous r=0.826 (p <0.0001 for both).

Conclusion: When scored by protocol standards, both the SS PGA and LFA-REAL^TM are reliable surrogates of commonly used endpoints in SLE trials. Both instruments are easy to score and understand, and could be employed as continuous or dichotomous endpoints. The LFA-REAL^TM provides an advantage of individualized scoring at the symptom or organ level.

Table 1. AUC of changes in LFA-REAL^TM and PGA in relation to SRI-4 and BICLA.

« Back to 2017 ACR/ARHP Annual Meeting

ACR Meeting Abstracts - https://acrabstracts.org/abstract/can-systemic-lupus-sle-disease-activity-be-consistently-scored-and-interpreted-with-simple-rapid-outcome-measures/