Dipeptidyl peptidase-4 inhibitors have been suspected to induce bullous pemphigoid (BP). The objective of this study was to compare the observed frequency of gliptin intake in a large sample of 1,787 BP patients diagnosed between 2012 and 2015 in France, with the expected frequency after indirect age standardization on 225,412 individuals extracted from the database of the National Healthcare Insurance Agency. The secondary objective was to assess the clinical characteristics and the course of gliptin-associated BP, depending on whether gliptin was continued or stopped. The observed frequencies of intake of the whole gliptin class and that of vildagliptin in the BP population were higher than those in the general population after age standardization (whole gliptin class: 6.0%; 95% confidence interval ¼ 4.9e7.1% vs. 3.6%, observed-to-expected drug intake ratio ¼ 1.7; 95% confidence interval ¼ 1.4e2.0; P < 0.0001; vildagliptin ¼ 3.3%; 95% confidence interval ¼ 2.5e4.1% vs. 0.7%, ratio ¼ 4.4; 95% confidence interval ¼ 3.5e5.7; P < 0.0001). The association of any gliptinþmetformin was also higher than in the general population, ratio ¼ 1.8 (95% confidence interval ¼ 1.3e2.4; P < 0.0001). Gliptin-associated BP had no specific clinical characteristics. Gliptin was stopped in 48 (45.3%) cases. Median duration to achieve disease control, rate, and delay of relapse were not different whether gliptin was stopped or continued. This study strongly supports the association between gliptin intake, particularly vildagliptin, and the onset of BP.
Summary Background The Bullous Pemphigoid Disease Area Index (BPDAI) score has been proposed to provide an objective measure of bullous pemphigoid (BP) activity. Objectives The objective of this study was to calculate BPDAI cut‐off values defining mild, moderate and severe BP. We also aimed to assess the interrater reliability and correlation with the number of daily new blisters, and anti‐BP180 and anti‐BP230 antibodies. Methods Severity scores were recorded by two blinded investigators. Anti‐BP180 and anti‐BP230 antibodies were measured using an enzyme‐linked immunosorbent assay (ELISA). Cut‐off values defining mild, moderate and severe subgroups were calculated based on the 25th and 75th percentiles of the BPDAI score. Results In total, 285 patients with BP were enrolled from 50 dermatology departments in Europe. Median BPDAI activity was 37·5 points (range 0–164). Cut‐off values corresponding to the first and third quartiles of the BPDAI score were 20 and 57, respectively; thus, these values were used to define mild (≤ 19), moderate (≥ 20 and ≤ 56) and severe (≥ 57) BP. The median BPDAI score for patients with ≤ 10 daily new blisters was 26 [interquartile range (IQR) 17–45], and for patients with > 10 daily new blisters the median score was 55 (IQR 39–82). The BPDAI intraclass correlation coefficient measured at baseline was 0·97 and remained higher than 0·90 up to month 6. The improvement in the BPDAI score was correlated with the absolute decrease in anti‐BP180 ELISA value (Spearman’s rank r = 0·34, P < 0·004), but not with anti‐BP230 antibodies (r = 0·17, P = 0·15). Conclusions This study suggests cut‐off values of 20–57 for BPDAI to distinguish mild, moderate and severe BP, and confirms that it is a robust tool to assess BP severity precisely.
Background The objective was to assess the response rate and survival of patients with metastatic mucosal melanoma (MM) and uveal melanoma (UM) treated with anti-CTLA-4 or anti-PD-1 monoclonal antibodies (mAbs). Methods A multicenter retrospective study was performed in 25 dermatology departments in France. All patients with stage III-C to IV MM or UM who were treated with anti-CTLA-4 or anti-PD-1 mAbs between 2008 and 2016 were included and compared after adjustment for main prognostic factors with a second cohort of patients treated with chemotherapy. Tumor response was evaluated according to RECIST v. 1.1 criteria at Week 12. Results Four-hundred-and-thirty-nine patients were included, 229 MM (151 immunotherapy, 78 chemotherapy) and 210 UM (100 immunotherapy, 110 chemotherapy). Response rates of MM patients treated with immunotherapy were 18/151 (11.9%; 95% CI:7.2%-18.2%), versus 11/78 (14.1%, 95% CI:7.3%-23.8%) in patients treated with chemotherapy (p=0.87). No tumor response was observed in UM patients treated with immunotherapy, versus 4/110 responses (3.6%, 95% CI:1.0-9.0%) in patients treated with chemotherapy (p=0.15). The adjusted overall survival (OS) of MM patients treated with immunotherapy was longer than that of patients treated with chemotherapy HR=0.62 (95% CI: 0.43-0.91), p=0.014, with an unadjusted median OS of 15.97 months [interquartile range (IQR)=6.89-27.11] and 8.82 months [IQR=5.02-14.92], respectively. The adjusted OS of UM patients treated with immunotherapy was not significantly different from that of patients treated with chemotherapy (HR=0.98, 95% CI: 0.66–1.44) p=0.92, with an unadjusted median OS of 13.38 months [IQR=6.03-29.57] and 11.02 months [IQR=6.13-23.93], respectively. Conclusion Immunotherapy significantly improves OS for MM. The prognosis of metastatic UM remains poor.
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