Assessment of the Effects of Rituximab Monotherapy on Different Subsets of Circulating T-Regulatory Cells and Clinical Disease Severity in Severe Pemphigus Vulgaris.

BACKGROUND: Robust evidence for the efficacy of rituximab monotherapy in pemphigus is lacking. The effects of rituximab on T-regulatory cells (Tregs) in pemphigus have not been studied. OBJECTIVE: The primary objective was to assess the efficacy of rituximab monotherapy in severe pemphigus vulgaris. The secondary objectives were to assess whether counts of different subsets of Tregs in the peripheral blood correlate with baseline clinical severity and whether clinical response in severe pemphigus is associated with an alteration in the Treg count. METHODS: Eighteen eligible subjects with severe pemphigus vulgaris were recruited and were treated with 1 g of intravenous rituximab on days 0 and 15. Efficacy was assessed in terms of disease control, time to disease control, complete remission off therapy, and relapse. Flow cytometric analysis of CD4+CD25+FoxP3, IL-10-secreting Tr1, and TGF-ß secreting Th3 regulatory cells was performed. Clinical evaluation and flow cytometric analysis of Tregs was performed periodically until follow-up at 26 weeks. RESULTS: Rituximab monotherapy was able to induce complete remission in all but 5 (68.75%) patients and was well tolerated. No direct relationship between clinical severity and CD4+CD25+FoxP3 cell counts was found. There were inverse correlations between serially measured values of the cutaneous and mucosal Autoimmune Bullous Skin Disorder Intensity Score (ABSIS) and Th3 cell count. CONCLUSION: Rituximab is a safe and effective monotherapy option for severe pemphigus. As the immunological findings were somewhat different from those observed in other autoimmune conditions treated with rituximab, further studies are required to substantiate the findings of our study in pemphigus patients.