Kridin K, et al. - Researchers quantified the link between dipeptidyl-peptidase 4 (DPP-4) inhibitor use and the development of bullous pemphigoid (BP), and studied the clinical features and history of patients with DPP-4 inhibitor–associated BP. They found an increased risk of BP associated with the exposure to vildagliptin and, to a lesser extent, linagliptin. This finding could be the explanation for an increasing incidence of BP in Israel. Based on these findings, they recommended consideration of DPP-4 inhibitor discontinuation in diabetic individuals with a diagnosis of BP.

Methods

• This was a retrospective case-control study.
• Participants were identified from a tertiary care referral center for autoimmune bullous diseases in northern Israel.
• Researchers assessed the intake of different DPP-4 inhibitor agents and metformin as well as the occurrence of BP among 82 consecutive patients with diabetes and immunopathologically validated BP (diagnosis period: January 1, 2011–December 31, 2017) and 328 age-, sex-, and ethnicity-matched control participants with diabetes but free of BP.
• Clinical and immunological features, laboratory analyses, treatments, and clinical outcomes were compared between patients with diabetes and BP and exposure to DPP-4 inhibitors followed up for a median of 2.0 years vs other patients with diabetes and BP who were not exposed to DPP-4 inhibitors.

Results

• They observed a three-fold increased risk for BP (adjusted odds ratio [OR], 3.2; 95% CI, 1.9-5.4) in association with DPP-4 inhibitor intake.
• Data showed that 10.7 (95% CI, 5.1-22.4) and 6.7 (95% CI, 2.2-19.7), respectively, were the adjusted ORs for vildagliptin and linagliptin.
• The link between DPP-4 inhibitor use and BP was independent of the use of metformin and was found to be stronger among male (OR, 4.46; 95% CI, 2.11-9.40) vs female (OR, 1.88; 95%, CI 0.92-3.86) patients; patients aged < 70 years exhibited the strongest link (OR, 5.59; 95% CI, 1.73-18.01).
• Compared with those with BP who had not been exposed to DPP-4 inhibitor, higher mucosal involvement (22.2% vs 6.5%; P=0.04) and lower mean (SD) peripheral eosinophil counts (399.8 [508.0] vs 1117.6 [1847.6] cells/μL; P=0.01) were observed among patients with DPP-4 inhibitor–associated BP.
• Improved clinical outcomes were reported following DPP-4 inhibitor discontinuation.