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

Summary 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 ( ROR s). 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.