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Developing biomarkers for predicting clinical relapse in pemphigus patients treated with rituximab
Lauren N Albers1, Yuan Liu2, Na Bo2
1Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia.
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.
