Dipeptidyl-peptidase IV inhibitor (DPP4i) confers increased odds of bullous pemphigoid even years after drug initiation

• Published in: Archives of Dermatological Research Vol. 315; no. 1; pp. 33 - 39
• Main Authors: Kridin, Khalaf, Avni, Orly, Damiani, Giovanni, Tzur Bitan, Dana, Onn, Erez, Weinstein, Orly, Cohen, Arnon D.
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.01.2023; Springer Nature B.V
• Subjects: Bullous pemphigoid; Case-Control Studies; Dermatology; Diabetes; Diabetes mellitus; Diabetes Mellitus, Type 2 - drug therapy; Diabetes Mellitus, Type 2 - epidemiology; Dipeptidyl-peptidase IV; Dipeptidyl-Peptidase IV Inhibitors - adverse effects; Humans; Hypoglycemic Agents - adverse effects; Medicine; Medicine & Public Health; Original Paper; Pemphigoid, Bullous - chemically induced; Pemphigoid, Bullous - epidemiology; Peptidase; DPP4i; Bullous pemphigoid; BP; Gliptin
• DOI: 10.1007/s00403-021-02317-9
• ISSN: 1432-069X; 0340-3696

The timing pattern in which dipeptidyl-peptidase IV inhibitors (DPP4i) confer the risk of bullous pemphigoid (BP) is unknown. To investigate the odds of BP following exposure to DPP4i and to perform a duration-response analysis evaluating the risk of BP in relation to the duration of exposure to the culprit drug. A population-based nested case–control study was performed comparing diabetic patients with BP ( n  = 1458) with age-, sex- and ethnicity-matched diabetic control subjects ( n  = 6051) with respect to the prevalence of exposure to DPP4i. Adjusted odds ratios (ORs) were estimated by logistic regression. Overall exposure to DPP4i was associated with an 80% increase in the odds of subsequent BP (OR, 1.81; 95% CI, 1.46–2.08; P  < 0.001). In an intraclass analysis, the odds of BP were increased in association with vildagliptin (OR, 3.40; 95% CI, 2.69–4.29; P  < 0.001) and sitagliptin (OR, 1.56; 95% CI, 1.33–1.84; P  < 0.001). In a duration-response analysis, the highest likelihood of BP was found 1–2 years after commencing the drug (OR, 2.66; 95% CI, 1.97–3.59; P  < 0.001). The odds of BP were increased across all time periods and retained its statistical significance even ≥ 6 years after the drug initiation (OR, 1.44; 95% CI, 1.09–1.91; P  = 0.011). Relative to other diabetic patients with BP, patients with DPP4i-associated BP were more likely to be admitted to inpatient dermatologic wards (OR, 1.66; 95% CI, 1.30–2.13; P  < 0.001) and had higher mean(SD) numbers of outpatient dermatologist visits (14.7[14.8] vs. 12.3[13.2], respectively; P  = 0.006). DPP4i should be suspected as a predisposing factor for BP even numerous years after the drug initiation.