Subtype and Racial Erythema Variation for Cutaneous Lupus Trials.

Importance: Regulatory guidance and standardization of disease outcome measures are essential to improve cutaneous lupus erythematosus (CLE) trial design and enhance the diversity of trial participants.

Objective: To assess variability in erythema presentation across CLE subtypes and among race and ethnicity groups to determine whether these potential differences affect patient eligibility for erythema trials.

Design, setting, and participants: This cross-sectional study included 377 patients with CLE enrolled in the University of Pennsylvania Cutaneous Lupus Erythematosus Database from January 2007 to December 2023. Data analyses were performed from December 2023 to February 2024.

Exposure: Race and CLE subtype.

Main outcomes and measures: Mean erythema calculated per the Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)-Activity total score divided by areas affected; then, the result was categorized as pink (1.00-1.49) or red (≥1.50) as surrogate estimates of scores per the Cutaneous Lupus Activity Investigator Global Assessment (CLA-IGA).

Results: The total study cohort included 377 adult patients with CLE (mean [SD; range] age, 45.2 [14.8; 18.4-88.8] years; 305 females [80.9%] and 72 males [19.1%]; 115 Black [30.5%], 228 White [60.5%], 34 patients of other races [9.0%; Asian, multiple races, Native American/Pacific Islander, or unknown], and 11 of Hispanic/Latino ethnicity [2.9%]). The most common CLE subtype was chronic CLE (CCLE), affecting 243 patients (64.5%), followed by subacute CLE (SCLE) in 103 patients (27.3%) and acute CLE (ACLE) in 31 patients (8.2%). Significant differences were observed in average erythema across subtypes, with mean (SD) SCLE of 1.62 (0.39) and hypertrophic CCLE of 1.78 (0.25) as the only subtypes routinely classified as red. Significant differences were also observed by race and ethnicity: mean (SD) erythema score in White patients was red (1.58 [0.45]) more frequently than in Black patients (1.36 [0.40]) and patients of other races (1.30 [0.39]), in whom, on average, it was scored as pink. Importantly, among patients who would meet typical CLASI entry criteria (score ≥8) for clinical trials, erythema in more Black patients than in White patients was classified as pink (42% [96 patients] vs 24% [28 patients]), which suggests exclusion from trial participation when a baseline of red lesions is required.

Conclusions and relevance: The findings of this cross-sectional study suggest that using average erythema scores per the CLA-IGA scale imposes substantial limitations on trial eligibility, specifically by race and subtype. Given the critical need to standardize CLE trial outcome measures and increase diverse representation in clinical trials, our findings support the use of the CLASI as the primary scoring tool to determine erythema trial eligibility.