270 Vildagliptin significantly increases the risk of bullous pemphigoid: A Finnish nationwide registry study

Abstract

Bullous pemphigoid (BP) is the most common autoimmune blistering skin disease. It causes intense pruritus and blistering, which have extensive effects on patients quality of life. The incidence of BP is increasing, although it is not yet known why. In recent years, a theory has emerged that BP may be triggered by the use of dipeptidyl peptidase 4 (DPP-4) inhibitors in the treatment of diabetes. Our nationwide study was designed to investigate the association between the use of diabetes drugs (excluding insulin) and BP, by analysis of Finnish registry data for 3397 BP patients and 12941 patients with basocellular carcinoma as controls. After adjusting for diabetes and several neurological disorders, the use of any DPP-4 inhibitor was associated with a significantly increased risk of BP (adjusted OR 2.19, 95% confidence interval [CI] 1.513.11) compared with the control population. The use of the DPP-4 inhibitor vildagliptin was associated with ten-fold elevated risk for BP (adjusted OR 10.4, 95% CI 4.5623.80). The mean latency from vildagliptin exposure to BP diagnosis was 449 days (range 36-729 days). The use of vildagliptin had no impact on patient age at BP diagnosis. Combinations of the DPP-4 inhibitors sitagliptin and vildagliptin with metformin were also associated with increased risk of BP (adjusted OR 2.40, 95% CI 1.224.73 and 6.71, 95% CI 2.0022.50, respectively). Other diabetes drugs and metformin alone were not associated with increased risk of BP. In conclusion, our nationwide registry study demonstrates a significantly increased risk of BP following the use of vildagliptin. Importantly, the long latency period between drug use and BP diagnosis strongly suggests a temporal association between preceding vildagliptin use and subsequent onset of BP.