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.
Background Corticosteroids (CS) with or without adjuvant immunosuppressant agents are standard treatment for pemphigus vulgaris (PV). The efficacy of adjuvant therapies in minimizing steroid-related adverse events (AEs) is unproven. Objectives To utilize data collected in a French investigator-initiated, phase III, open-label, randomized controlled trial to demonstrate the efficacy and safety of rituximab and seek approval for its use in PV.Methods This was an independently conducted post hoc analysis of the moderateto-severe PV subset enrolled in the Ritux 3 study. Patients were randomized to rituximab plus 0Á5 or 1Á0 mg kg À1 per day prednisone tapered over 3 or 6 months, or 1Á0 or 1Á5 mg kg À1 per day prednisone alone tapered over 12 or 18 months, respectively (according to disease severity). The primary end point was complete remission at month 24 without CS (CRoff) for ≥ 2 months, and 24month efficacy and safety results were also reported.Results At month 24, 34 of 38 patients (90%) on rituximab plus prednisone achieved CRoff ≥ 2 months vs. 10 of 36 patients (28%) on prednisone alone. Median total cumulative prednisone dose was 5800 mg in the rituximab plus prednisone arm vs. 20 520 mg for prednisone alone. Eight of 36 patients (22%) who received prednisone alone withdrew from treatment owing to AEs; one rituximab-plus-prednisone patient withdrew due to pregnancy. Overall, 24 of 36 patients (67%) on prednisone alone experienced a grade 3/4 CS-related AE vs. 13 of 38 patients (34%) on rituximab plus prednisone. Conclusions In patients with moderate-to-severe PV, rituximab plus short-term prednisone was more effective than prednisone alone. Patients treated with rituximab had less CS exposure and were less likely to experience severe or life-threatening CS-related AEs.
What's already known about this topic?Rituximab in pemphigus vulgaris, D.M. Chen et al. 1113 CI, confidence interval; CRoff, complete remission off prednisone therapy; IQR, interquartile range; N/A, not applicable; CRmin, complete remission on minimal prednisone therapy (prednisone dose ≤ 10 mg per day). a No adjustment for multiplicity was made for any secondary end points and the P-values should be interpreted with caution. b 95% confidence interval (CI) calculated using the corrected Newcombe interval. c P-value calculated using Fisher's exact test with mid-P correction. d P-value calculated using Mann-Whitney U-test.
Vitiligo may thus emerge and/or progress during treatment with various biological agents, mainly TNFα inhibitors and could be a new paradoxical skin reaction. De novo vitiligo displays a favourable outcome when maintaining the biological agent, whereas the prognosis seems worse in cases of pre-existing vitiligo.
(ABSIS) scores have been proposed to provide an objective measure of pemphigus activity. These scores have been evaluated only on already treated patients mainly with mild to moderate activity. The objective was to assess the interrater reliability of ABSIS and PDAI scores and their correlation with other severity markers in a large international study. Consecutive patients with newly diagnosed pemphigus were enrolled in 31 centers. Severity scores were recorded during a 24-month period by the same two blinded investigators. Serum was collected at each visit for ELISA measurement of anti-desmoglein antibodies. The intraclass correlation coefficient (ICC) and Spearman rank correlation coefficient were calculated. A total of 116 patients with pemphigus vulgaris (n ¼ 84) or pemphigus foliaceus (n ¼ 32) were
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