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.

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.

• Authors: J Béné, G Moulis, I Bennani, M Auffret, P Coupe, S Babai, D Hillaire-Buys, J Micallef, S Gautier, French Association of Regional PharmacoVigilance Centres
• Journal: The British journal of dermatology (Br J Dermatol) Vol. 175 Issue 2 Pg. 296-301 (Aug 2016) ISSN: 1365-2133 [Electronic] England
• PMID: 27031194 (Publication Type: Comparative Study, Journal Article)
• Copyright: © 2016 British Association of Dermatologists.

Chemical References

• Dipeptidyl-Peptidase IV Inhibitors

Topics

• 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, epidemiology)
• Pharmacovigilance
• Risk Factors
• Safety-Based Drug Withdrawals (statistics & numerical data)