J K Presto1,2, L G Okon1,2, R Feng3, D J Wallace4, R Furie5, D Fiorentino6, V P Werth1,2. 1. Corporal Michael J. Crescenz Veterans Affairs Medical Center (Philadelphia), Philadelphia, PA, U.S.A. 2. Department of Dermatology at the Perelman School of Medicine at the University of Pennsylvania, Pennsylvania, PA, U.S.A. 3. Biostatistics and Epidemiology at the Hospital of the University of Pennsylvania, Pennsylvania, PA, U.S.A. 4. Division of Rheumatology, Cedars-Sinai Medical Center, Los Angeles, CA, U.S.A. 5. Division of Rheumatology, Northwell Health, Great Neck, NY, U.S.A. 6. Department of Dermatology, Stanford University School of Medicine, Stanford, CA, U.S.A.
Abstract
BACKGROUND: R333 is a topical janus kinase and spleen tyrosine kinase inhibitor being evaluated for discoid lupus erythematosus (DLE) treatment. There is no validated measure to assess the area of active DLE lesions. OBJECTIVES: To evaluate R333 efficacy and assess a technique to measure responsiveness. METHODS:Fifty-four patients with DLE were randomized in a double-blind design to R333 or placebo. Primary end point was the proportion of patients achieving ≥ 50% decrease in erythema and scale based on lesional Cutaneous Lupus Erythematosus Disease Area and Severity IndexTM for all treated lesions at week 4. Two-dimensional (2D) area measurements for each lesion were recorded at baseline and weeks 1-6. Eighty-eight photographs (44 pre- and 44 post-treatment) were obtained from the trial and change in size of active areas was analysed by computerized planimetry and physician-assessed area change (PAAC). RESULTS:Thirty-six patients were randomized to R333 and 18 patients were randomized to placebo. Primary end point was not achieved. There was a strong association between lesion activity and physician global assessment (P < 0·001). Photos of 42 patients assessed by computerized planimetry demonstrated excellent inter- and intra-rater reliability. Area change by computerized planimetry showed a strong correlation with PAAC (Spearman r = 0·72). Area change by 2D measurements showed a weak correlation with PAAC (Spearman r = 0·29). CONCLUSIONS: Four weeks of R333 treatment did not result in significant improvement in lesion activity. Lesion activity and area change using computerized planimetry are better determinants of responsiveness than area change using 2D measurements. Published [2018]. This article is a U.S. Government work and is in the public domain in the U.S.A.
RCT Entities:
BACKGROUND: R333 is a topical janus kinase and spleen tyrosine kinase inhibitor being evaluated for discoid lupus erythematosus (DLE) treatment. There is no validated measure to assess the area of active DLE lesions. OBJECTIVES: To evaluate R333 efficacy and assess a technique to measure responsiveness. METHODS: Fifty-four patients with DLE were randomized in a double-blind design to R333 or placebo. Primary end point was the proportion of patients achieving ≥ 50% decrease in erythema and scale based on lesional Cutaneous Lupus Erythematosus Disease Area and Severity IndexTM for all treated lesions at week 4. Two-dimensional (2D) area measurements for each lesion were recorded at baseline and weeks 1-6. Eighty-eight photographs (44 pre- and 44 post-treatment) were obtained from the trial and change in size of active areas was analysed by computerized planimetry and physician-assessed area change (PAAC). RESULTS: Thirty-six patients were randomized to R333 and 18 patients were randomized to placebo. Primary end point was not achieved. There was a strong association between lesion activity and physician global assessment (P < 0·001). Photos of 42 patients assessed by computerized planimetry demonstrated excellent inter- and intra-rater reliability. Area change by computerized planimetry showed a strong correlation with PAAC (Spearman r = 0·72). Area change by 2D measurements showed a weak correlation with PAAC (Spearman r = 0·29). CONCLUSIONS: Four weeks of R333 treatment did not result in significant improvement in lesion activity. Lesion activity and area change using computerized planimetry are better determinants of responsiveness than area change using 2D measurements. Published [2018]. This article is a U.S. Government work and is in the public domain in the U.S.A.
Authors: Joel M Guthridge; Rufei Lu; Ly Thi-Hai Tran; Cristina Arriens; Teresa Aberle; Stan Kamp; Melissa E Munroe; Nicolas Dominguez; Timothy Gross; Wade DeJager; Susan R Macwana; Rebecka L Bourn; Stephen Apel; Aikaterini Thanou; Hua Chen; Eliza F Chakravarty; Joan T Merrill; Judith A James Journal: EClinicalMedicine Date: 2020-03-04