541 Anchoring the CLASI-A, a clinical outcome assessment (COA), to the patients’ perspective of their disease

Abstract

The CLASI-A is a validated tool for physicians to quantify skin disease activity in cutaneous lupus and has been successfully used in several phase 1-3 clinical trials. Here, we evaluated the CLASI-A based on recent guidance from the FDA (USA) to focus on “meaningful within-patient change (i.e., improvement or deterioration from the patients’ perspective) in the concepts assessed by COAs.” We performed a prospective study on 250 patients with cutaneous lupus (1-25 clinic visits each). At nearly every visit, we recorded both a CLASI-A score by the physician (0-70; 70 is worst, 0 is best) and a visual analogue scale by the patient (ptVAS) to indicate his or her perception of cutaneous disease activity (0-10; 0 is worst, 10 is best), i.e., a patient global impression of severity (PGIS). At the initial visit, CLASI-A and ptVAS strongly correlated (Spearman’s rho=-0.226, p=0.0003). To assess within-patient change for each patient with >1 visit (n=229), we selected the pairs of visits with the largest and the smallest differences in ptVAS scores (range of Δs = -10 to +10, in a bell-shaped distribution, two data points per patient). We grouped these data points into five categories according to ΔptVAS: [-10,-6] (markedly worse from the patient’s perspective), [-5,-2] (moderately worse), [-1,1] (minimal or no change), [2,5] (moderately better), and [6,10] (markedly better). Changes in CLASI-A scores between the same two visits differed amongst the five ΔptVAS categories (p<0.0001 by ANOVA on ranks). Empirical cumulative distribution function (eCDF) curves and probability density function (PDF) curves for the changes in CLASI scores showed progressive improvements in CLASI-A as the patients’ perception improved across the five ΔptVAS categories. Moderate worsening or improvement from the patients’ perspectives corresponded to median changes in the CLASI-A score of +16.7% and -32.1%. Our data indicate that the CLASI-A can be anchored to the ptVAS, to assess meaningful within-patient changes in cutaneous disease from the patients’ perspective.