Bullous Pemphigoid and Diabetes medications: A disproportionality analysis based on the FDA Adverse Event Reporting System

Abstract

Background: The world's first Diabetes Medications (Insulin) was marketed in October 1923. Some studies suggested the association of diabetes medications with Bullous Pemphigoid (BP), especially the Dipeptidyl Peptidase 4 (DPP-4) inhibitors. The study aims to detect an association between diabetes medications (focusing on DPP-4 inhibitors) and bullous pemphigoid based on FDA Adverse Event Reporting System (FAERS). Methods: All spontaneous reports of diabetes medications inhibitors-related BP recorded in the FAERS between March 2004 and August 2020 were included in the present study. Disproportionality analysis was performed to find the signal between diabetes medications and BP. The Chi-Squared with Yates' correction (χ 2 Yates), proportional reporting ratio (PRR) and the lower limit of the 95% confidence interval of the Reporting Odds Ratio (ROR025) were calculated as a measure. A signal was detected when ROR025 > 1, PRR > 2, χ 2 Yates > 4 and at least 3 cases. Results: There were 3770 reports for BP in FAERS. The strongest signal for diabetes medications-BP association were DDP-4 inhibitors (

Lisinopril prevents bullous pemphigoid induced by dipeptidyl peptidase 4 inhibitors via the Mas receptor pathway

“…Further, in the FAERS data, seven DPP4 inhibitors, i.e., vildagliptin, linagliptin, sitagliptin, alogliptin, teneligliptin, and saxagliptin, were identified, and we observed a significant association between the use of these compounds and BP incidence, independent of selectivity towards DPP8/9. These results are consistent with those of a previous study based on FAERS data, randomized controlled trials and Meta-analysis ( 39 , 44 , 45 ). These data may indicate that the inhibition of DPP4 enzyme activity increased the incidence of DPP4 inhibitor-induced BP.…”

“…Therefore, in the present study, we used adverse event data from the FAERS database, on the basis of which several unexpected drug-drug interactions were identified as confounding factors ( 7 – 10 ). Our analysis in this regard not only suggested that DPP4 inhibitors could cause BP, as indicated by previous studies ( 39 , 40 ), but also indicated that lisinopril could suppress DPP4 inhibitor-induced BP. Conversely, the anti-PD1/PDL1 antibody group (nivolumab, pembrolizumab, cemiplimab, atezolizumab, avelumab, and durvalumab) showed increased risk of BP (ROR = 16, Z score = 48), and combination treatment with lisinopril did not affect their odds ratios (ROR=1.6, Z score = 1.2).…”

Drugs‐associated with red man syndrome: An integrative approach using disproportionality analysis and Pharmip

“…14 ROR and PRR were calculated per the methods mentioned in different pharmacovigilance retrospective studies. [15][16][17] A value of ROR-1.96SE >1 (SE-Standard Error) and PRR ≥2 were considered as the threshold value, above which it is regarded as a positive signal.…”

“…It aims to provide clean and curated access to the underlined reported adverse events and count reports stratified to an extraction condition 14 . ROR and PRR were calculated per the methods mentioned in different pharmacovigilance retrospective studies 15–17 . A value of ROR‐1.96SE >1 (SE‐ Standard Error) and PRR ≥2 were considered as the threshold value, above which it is regarded as a positive signal.…”