Bullous pemphigoid and dipeptidyl peptidase IV inhibitors: a case-noncase study in the French Pharmacovigilance Database

Br J Dermatol. 2016 Aug;175(2):296-301. doi: 10.1111/bjd.14601. Epub 2016 Jul 19.

Abstract

Background: Inhibitors of dipeptidyl peptidase (DPP)-IV have been suspected in the onset of bullous pemphigoid for several years now. However, comparative studies assessing the link between DPP-IV inhibitor exposure and bullous pemphigoid have not yet been performed.

Objectives: To detect, from the French Pharmacovigilance Database (FPVD), a signal of risk of bullous pemphigoid during DPP-IV inhibitor exposure by comparative study.

Methods: All spontaneous reports of DPP-IV inhibitor-related bullous pemphigoid recorded in the FPVD between April 2008 and August 2014 were described. We conducted disproportionality analyses (case-noncase method) to assess the link between DPP-IV inhibitors and bullous pemphigoid, calculating reporting odds ratios (RORs). We also compared DPP-IV inhibitor-induced bullous pemphigoid reports rated per million defined daily doses dispensed during the study period.

Results: Among 217 331 spontaneous adverse drug reaction reports registered in the FPVD, 1297 involved DPP-IV inhibitors. Among these observations, 42 were bullous pemphigoid (vildagliptin, n = 31; sitagliptin, n = 10; saxagliptin, n = 1). The ROR for pooled DPP-IV inhibitors was 67·5 [95% confidence interval (CI) 47·1-96·9]. Disproportionality was also observed for each DPP-IV inhibitor: vildagliptin (ROR 225·3, 95% CI 148·9-340·9), sitagliptin (ROR 17·0, 95% CI 8·9-32·5) and saxagliptin (ROR 16·5, 95% CI 2·3-119·1). Analyses adjusted on dispensing data led to similar results.

Conclusions: These data confirm a strong signal for an increased risk of bullous pemphigoid during DPP-IV inhibitor exposure. This adverse drug reaction is observed for each DPP-IV inhibitor, suggesting a class effect. The signal was higher with vildagliptin than with the other DPP-IV inhibitors.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Dipeptidyl-Peptidase IV Inhibitors / adverse effects*
  • Drug Eruptions / etiology*
  • Female
  • France / epidemiology
  • Humans
  • Male
  • Middle Aged
  • Pemphigoid, Bullous / chemically induced*
  • Pemphigoid, Bullous / epidemiology
  • Pharmacovigilance
  • Risk Factors
  • Safety-Based Drug Withdrawals / statistics & numerical data

Substances

  • Dipeptidyl-Peptidase IV Inhibitors