Presentation (CTI)

OBJECTIVES: Treatment options for cutaneous lupus erythematosus (CLE) are limited, as there is a lack of evidence supporting the use of the few therapeutic options that exist. As novel therapies for active CLE continue to emerge, consistent disease definitions are essential for trial comparability, evidence synthesis, and informed healthcare decision-making. This systematic review assessed heterogeneity in the definitions of active CLE used across clinical trials.
METHODS: MEDLINE® and Embase® were searched for English-language clinical trials published between 2011 and 2026 that evaluated treatment efficacy in active CLE. Study selection was conducted using Nested Knowledge’s GPT-4-powered, human-in-the-loop AI-assisted framework. Records were screened independently by AI and a human reviewer, with conflicts resolved by an independent human reviewer. Definitions of active CLE were extracted from eligible trials.
RESULTS: Of 1,621 records identified, 26 clinical trials met the inclusion criteria. Fifteen trials (57.7%) defined active CLE using the CLE Disease Area and Severity Index-Activity score (CLASI-A) or modified/revised CLASI-A criteria. The most frequent thresholds were CLASI-A ≥8 (6/15, 40.0%) and CLASI-A ≥10 (4/15, 26.7%); the remaining trials used CLASI-A ≥4, CLASI-A ≥6, revised CLASI-A ≥4, or modified/revised CLASI-A ≥6. Standard therapy trials generally used lower thresholds, whereas biologics’ trials consistently employed higher thresholds i.e. CLASI-A ≥8 or ≥10. Trials of oral targeted therapies showed greater variability, with thresholds ranging from modified CLASI-A ≥6 to CLASI-A ≥10. Remaining 11 trials used alternative definitions by study authors, including the presence of at least one active lesion, Cutaneous Lupus Activity Investigator’s Global Assessment, histopathological or medical history criteria, or unspecified criteria.
CONCLUSIONS: Definitions of active CLE vary substantially across clinical trials, which may limit cross-trial comparisons and complicate interpretation of treatment efficacy. Establishing an internationally standardized definition of active CLE would improve consistency in future clinical research and strengthen therapeutic evaluation.