JWM is supported by the Intramural Research Program of the NIH, NIDCR. In addition, the authors express their sincere appreciation for the opportunity to collaborate with the WWOM VII Steering Committee. response to biologic therapy is usually sparse. Two RCTs support use of rituximab, one supports use of IVIg, and one pilot study suggests intralesional injection of autologous platelet-rich plasma aids healing of oral PV lesions. As oral lesions of pemphigus and pemphigoid can be refractory to systemic therapy, Coelenterazine drug trials including biologic therapies should document details regarding response of the oral lesions to therapy. conducted randomized comparative observer-blinded pilot study that compared two rituximab dosing regimens for the treatment pemphigus (Kanwar et al., 2014). Patients with active PV (n=15) or PF (n=7) who were treatment-naive, resistant to previous therapies, or who had severe disease were recruited from a dermatology department in a tertiary care setting in India. They were randomized to receive either two doses of 500 or 1000 mg rituximab at an interval of 15 days and were followed for 48 weeks. The primary endpoint was clinical efficacy between treatments in terms of early (time to disease control and time to complete consolidation phase) and late end points [partial response (PR) and complete response, (CR)] around the Ikeda severity score scale as assessed by an examiner blinded to treatment group (Ikeda et al., 2003). No significant adverse events (SAEs) were recorded in either group, though AEs including moderate infusion reactions, upper respiratory tract infections, diarrhea, striae and acneiform eruptions were seen in both groups. The mean number of AEs was 1.36 in the 2500 mg group and 1.45 in the 21000 mg group. At week 40, the fall in Ikeda severity score was steeper in the 21000 mg group than in 2500 mg group (P = 0.049). Patients in the 2500 mg group received a significantly Coelenterazine higher cumulative dose of azathioprine (P = 0.018). ELISA indices of Coelenterazine Dsg1 and Dsg3 showed a statistically significant decline in the 21000 mg group only, and B cell repopulation occurred earlier 8 weeks earlier in the 2500 mg group. In 2017, Joly and colleagues published results from an open-label multicenter parallel RCT comparing oral prednisone alone versus rituximab and a short-term prednisone regimen to treat newly-diagnosed pemphigus (Joly et al., 2017). Pemphigus patients with PV (n=74) or PF (n=16) were recruited at 25 centers in France and randomized to one of 2 groups: oral prednisone alone starting at 1.0 or 1.5 mg/kg/day, tapered over 12C18 months (n=44), or 1000 mg intravenous rituximab on days 0 and 14, and a 500 mg dose at WAF1 months 12 and 18 combined with a short-term prednisone treatment of 1 1.0C1.5mg/kg/day tapered over 3C6 months (n=46). Stratification by severity of pemphigus was included in the randomization matrix, and moderate-to-severe pemphigus was defined as skin involvement of greater than 5% body surface area, or significant mucosal involvement Coelenterazine defined as more than ten mucosal erosions, or diffuse gingivitis or confluent large erosions, or involvement of two or more mucosal sites. Scoring of the oral mucosa was incorporated into the mucous membrane subsection of the Pemphigus Disease Area Index (PDAI) scoring tool, however, oral tissue subscores were not reported for this study (Dedee F. Murrell et al., 2008). Patients assigned to rituximab plus short-term prednisone had significantly fewer SAEs (mean 059 [SD 1.15]) than patients those assigned to prednisone alone (mean 1.20 [SD 125]), which was attributed to the lower cumulative steroid dose in the rituximab group. At the primary endpoint, month 24, 41 (89%) of 46 patients assigned to rituximab plus short-term prednisone were in complete remission off-therapy versus 15 (34%) of 44 assigned to prednisone alone (p 00001). The corresponding relative risk of success of is 2.61 (95% CI 171C399, p 00001). Data from this study demonstrate a clear benefit of rituximab as a first-line therapy for pemphigus patients, including those with severe oral mucosal manifestations. Inflammation is a significant factor in the feed-forward circuit of autoimmune disease. Tumor necrosis factor alpha (TNF-) is cytokine that has been detected in the skin lesions of patients with PV, and serum levels of TNF- have been correlated with disease activity. In 2015, Hall reported treatment of pemphigus patients using infliximab, an inhibitor of TNF- (Hall et al., 2015). This double-blinded, placebo-controlled trial was carried out at 6 centers in the United States. Ten patients received infusions of infliximab (5 mg kg) at weeks 0, 2, 6 and 14 while receiving standard-of-care with follow-up at weeks 10, 18, 22 and 26. Ten control group patients received infusions of placebo.

JWM is supported by the Intramural Research Program of the NIH, NIDCR