title: Bullous pemphigoid and dipeptidyl peptidase IV inhibitors: a case-noncase study in the French Pharmacovigilance Database.
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.
  
  
  OBJECTIVE
  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.
authors.affiliation: Centre Régional de Pharmacovigilance du Nord Pas-de-Calais, Univ.Lille, CHU Lille, F-59000, Lille, France.
authors.forename: J
authors.initials: J
authors.lastname: Béné
authors.affiliation: Service de Médecine Interne, CHU de Toulouse, Toulouse, France.|UMR 1027 INSERM-Université Paul Sabatier, Toulouse, France.|Centre d'Investigation Clinique 1436, CHU de Toulouse, France.
authors.forename: G
authors.initials: G
authors.lastname: Moulis
authors.affiliation: Service de Dermatologie, CHU de Toulouse, Toulouse, France.
authors.forename: I
authors.initials: I
authors.lastname: Bennani
authors.affiliation: Centre Régional de Pharmacovigilance du Nord Pas-de-Calais, Univ.Lille, CHU Lille, F-59000, Lille, France.
authors.forename: M
authors.initials: M
authors.lastname: Auffret
authors.affiliation: Service Pharmacie, Centre Hospitalier de Valenciennes, Valenciennes, France.
authors.forename: P
authors.initials: P
authors.lastname: Coupe
authors.affiliation: Centre Régional de PharmacoVigilance, Hôpital Henri Mondor, Assistance Publique Hôpitaux de Paris, Créteil, France.
authors.forename: S
authors.initials: S
authors.lastname: Babai
authors.affiliation: Centre Régional de PharmacoVigilance, Département de Pharmacologie Médicale et Toxicologie, Faculté de Médecine et CHRU, Montpellier, France.
authors.forename: D
authors.initials: D
authors.lastname: Hillaire-Buys
authors.affiliation: Centre Régional de PharmacoVigilance, Service de Pharmacologie Clinique et Pharmacovigilance, Assistance Publique des Hôpitaux de Marseille, Aix Marseille Université, Marseille, France.
authors.forename: J
authors.initials: J
authors.lastname: Micallef
authors.affiliation: Centre Régional de Pharmacovigilance du Nord Pas-de-Calais, Univ.Lille, CHU Lille, F-59000, Lille, France.
authors.forename: S
authors.initials: S
authors.lastname: Gautier
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D054873:Dipeptidyl-Peptidase IV Inhibitors / Q000009:adverse effects*; D003875:Drug Eruptions / Q000209:etiology*; D005260:Female; D005602:France / Q000453:epidemiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010391:Pemphigoid, Bullous / Q000139:chemically induced* / Q000453:epidemiology; D060735:Pharmacovigilance; D012307:Risk Factors; D056737:Safety-Based Drug Withdrawals / Q000706:statistics & numerical data
chemical_list: D054873:Dipeptidyl-Peptidase IV Inhibitors