Lauren N Albers1, Yuan Liu2, Na Bo2, Robert A Swerlick1, Ron J Feldman3. 1. Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia. 2. Department of Biostatistics and Bioinformatics, Rollins School of Public Health, Emory University, Atlanta, Georgia. 3. Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia. Electronic address: ron.j.feldman@emory.edu.
Abstract
BACKGROUND: Rituximab is an effective therapy for pemphigus, although relapses are common. OBJECTIVE: To identify biomarkers to predict relapse of pemphigus following rituximab treatment. METHODS: In this retrospective cohort study, 62 patients with pemphigus treated with 99 rituximab cycles provided longitudinal clinical scoring and biomarker data, including levels of CD19+ B cells, CD4+ T cells, and desmoglein 1 (Dsg1) and desmoglein 3 (Dsg3) autoantibodies. An extended time-variant Kaplan-Meier estimator and extended Cox model were applied. RESULTS: Relapse was rare before B-cell repopulation. Univariate analysis revealed low CD4 count (<400 cells/μL) to predict relapse (P < .001). A positive result of testing for Dsg1 (>20 IU) was predictive of relapse among patients with mucocutaneous disease (hazard ratio, 6.40; P = .019); a positive result of testing for Dsg3 (>20 IU) was predictive in patients with mucocutaneous and mucosal disease (hazard ratio, 32.92; P < .001). Multivariable analysis revealed that every CD4 value increase of 200 decreases the hazard ratio for relapse by 35% (P = .029). A positive result of testing for Dsg1 increases the risk for relapse by a factor of 12.32 in patients with mucocutaneous disease (P = .001); positive result of testing for Dsg3 increases risk for relapse by 28.38 in patients with mucosal and mucocutaneous disease (P = .006). LIMITATIONS: Limitations include the retrospective design and inconsistent follow-up. CONCLUSION: Relapse is associated with B-cell repopulation, low CD4+ T -cell count, and positive result of testing for Dsg1 and Dsg3.
BACKGROUND:Rituximab is an effective therapy for pemphigus, although relapses are common. OBJECTIVE: To identify biomarkers to predict relapse of pemphigus following rituximab treatment. METHODS: In this retrospective cohort study, 62 patients with pemphigus treated with 99 rituximab cycles provided longitudinal clinical scoring and biomarker data, including levels of CD19+ B cells, CD4+ T cells, and desmoglein 1 (Dsg1) and desmoglein 3 (Dsg3) autoantibodies. An extended time-variant Kaplan-Meier estimator and extended Cox model were applied. RESULTS: Relapse was rare before B-cell repopulation. Univariate analysis revealed low CD4 count (<400 cells/μL) to predict relapse (P < .001). A positive result of testing for Dsg1 (>20 IU) was predictive of relapse among patients with mucocutaneous disease (hazard ratio, 6.40; P = .019); a positive result of testing for Dsg3 (>20 IU) was predictive in patients with mucocutaneous and mucosal disease (hazard ratio, 32.92; P < .001). Multivariable analysis revealed that every CD4 value increase of 200 decreases the hazard ratio for relapse by 35% (P = .029). A positive result of testing for Dsg1 increases the risk for relapse by a factor of 12.32 in patients with mucocutaneous disease (P = .001); positive result of testing for Dsg3 increases risk for relapse by 28.38 in patients with mucosal and mucocutaneous disease (P = .006). LIMITATIONS: Limitations include the retrospective design and inconsistent follow-up. CONCLUSION: Relapse is associated with B-cell repopulation, low CD4+ T -cell count, and positive result of testing for Dsg1 and Dsg3.
Authors: Sandra Saschenbrecker; Ingolf Karl; Lars Komorowski; Christian Probst; Cornelia Dähnrich; Kai Fechner; Winfried Stöcker; Wolfgang Schlumberger Journal: Front Immunol Date: 2019-08-20 Impact factor: 7.561
Authors: G Genovese; C A Maronese; G Casazza; L Corti; L Venegoni; S Muratori; E Berti; D Fanoni; A V Marzano Journal: Clin Exp Dermatol Date: 2021-08-27 Impact factor: 4.481