Bullous pemphigoid induced by dipeptidyl peptidase-4 (DPP-4) inhibitors: a pharmacovigilance-pharmacodynamic/pharmacokinetic assessment through an analysis of the vigibase®

Carnovale, Carla; Mazhar, Faizan; Arzenton, Elena; Moretti, Ugo; Pozzi, Marco; Mosini, Giulia; Leoni, Olivia; Scatigna, M; Clementi, Emilio; Radice, Sonia

doi:10.1080/14740338.2019.1668373

Cited by 29 publications

(40 citation statements)

References 65 publications

(23 reference statements)

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“…The affinity data of a DPP-4i drug for the enzymes explain to some extent different levels of bullous pemphigoid reporting in our study (quantified as ROR) [7].…”

Section: Discussionmentioning

confidence: 55%

“…The author speculated that all DPP-4 inhibitors are selective for the DPP-4 enzyme, and the affinity for the DPP-4 enzyme may contribute to the risk of bullous pemphigoid. The affinity data of a DPP-4i drug for the enzymes explain to some extent different levels of bullous pemphigoid reporting in our study (quantified as ROR) [ 7 ].…”

Section: Discussionmentioning

confidence: 90%

“…Previous pharmacovigilance studies have revealed the association between DPP-4is and some particular adverse events [ 7 – 9 ]. To achieve the latest information about the safety profiles of DPP-4is, we queried an international SRS, namely FAERS, to characterize the reporting pattern of DPP-4is and map the entire spectrum of AEs by the pharmacovigilance approach.…”

Section: Introductionmentioning

confidence: 99%

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Adverse event profiles of dipeptidyl peptidase-4 inhibitors: data mining of the public version of the FDA adverse event reporting system

Huang

Jia²,

Sun

et al. 2020

BMC Pharmacol Toxicol

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Background To describe and analyze the patterns of adverse events associated with dipeptidyl peptidase-4 inhibitors (DPP-4is) (sitagliptin, saxagliptin, linagliptin, vildagliptin, and alogliptin) from the FDA Adverse Event Reporting System (FAERS) and to highlight areas of safety concerns. Methods Adverse events spontaneously submitted to the FAERS between 2004 Q1 to 2019 Q2 were included. The online tool OpenVigil 2.1 was used to query the database. The research relied on definitions of preferred terms (PTs) specified by the Medical Dictionary for Regulatory Activities (MedDRA) and the standardized MedDRA Queries (SMQ). The reporting odds ratio (ROR), with 95% confidence intervals (CIs) was calculated for disproportionality analysis. Results Over 16 years, a total of 9706 adverse event reports were identified. Alogliptin was excluded from further analysis due to insufficient sample size. Compared with the non-insulin antidiabetic drugs, the four DPP-4is were all disproportionately associated with four SMQs: “gastrointestinal nonspecific inflammation and dysfunctional conditions,” “hypersensitivity,” “severe cutaneous adverse reactions,” and “noninfectious diarrhoea”. As for PT level analyses, DPP-4is are associated with higher reporting of the gastrointestinal tract, pancreas, malignancies, infection, musculoskeletal disorders, general disorders, hypersensitivity, and skin AEs. Conclusions Data mining of the FAERS is useful for examining DPP-4 inhibitors-associated adverse events. The findings of the present study are compatible with clinical experience, and it provides valuable information to decision-makers and healthcare providers in clinical practice.

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“…The affinity data of a DPP-4i drug for the enzymes explain to some extent different levels of bullous pemphigoid reporting in our study (quantified as ROR) [7].…”

Section: Discussionmentioning

confidence: 55%

Section: Discussionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Adverse event profiles of dipeptidyl peptidase-4 inhibitors: data mining of the public version of the FDA adverse event reporting system

Huang

Jia²,

Sun

et al. 2020

BMC Pharmacol Toxicol

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“…In that year, Pasmatzi and coworkers described two cases of BP induced by vildagliptin [ 25 ]. Moreover, one hundred cases of BP due to this DPP-4i, and to others, such as sitagliptin, linagliptin, saxagliptin, teneligliptin, anagliptin, and alogliptin, have been reported [ 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 34 , 35 , 36 , 37 , 38 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 ] ( Table 1 ). Epidemiological evidence significantly supports the correlation of DPP-4i and BP onset.…”

Section: Trigger Factorsmentioning

confidence: 99%

Bullous Pemphigoid: Trigger and Predisposing Factors

et al. 2020

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Bullous pemphigoid (BP) is the most frequent autoimmune subepidermal blistering disease provoked by autoantibodies directed against two hemidesmosomal proteins: BP180 and BP230. Its pathogenesis depends on the interaction between predisposing factors, such as human leukocyte antigen (HLA) genes, comorbidities, aging, and trigger factors. Several trigger factors, such as drugs, thermal or electrical burns, surgical procedures, trauma, ultraviolet irradiation, radiotherapy, chemical preparations, transplants, and infections may induce or exacerbate BP disease. Identification of predisposing and trigger factors can increase the understanding of BP pathogenesis. Furthermore, an accurate anamnesis focused on the recognition of a possible trigger factor can improve prognosis by promptly removing it.

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“…Emerging evidence has established a relationship between DPP4i and the development of BP (OR, 2.13-97.69; Table S1). [42][43][44][45][46][47][48][49][50][51][52][53][54][55] Vildagliptin is the leading DPP4i to confer increased risk of BP The extracellular domain comprises dipeptidyl peptidase activity which selectively removes the X-proline or X-alanine dipeptide residues in the penultimate position from the NH 2 -terminus of polypeptide substrates. The extracellular catalytic domain of DPP4 serves as a binding site for substrates and inhibitors.…”

Section: Bullous Pemphi G Oid and Mucous Memb R Ane Pemphigoidmentioning

confidence: 99%

The role of Dipeptidyl Peptidase‐4 in cutaneous disease

Patel

Jones

Kridin

et al. 2020

Experimental Dermatology

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Dipeptidyl peptidase-4 (DPP4) is a multifunctional, type II transmembrane glycoprotein expressed on the cell surface of many tissues. 1,2 Its soluble form (aa 49-766) is also found in various bodily fluids (Figure 1). 3 CD26 is a cell surface marker with DPP4 enzymatic activity in its extracellular domain. For uniformity, we will use the term CD26 + or CD26 − to indicate the presence or absence of DPP4 as a cell surface marker but use DPP4 in reference to the enzyme and gene/protein expression. Dipeptidyl peptidase-4 is a serine exopeptidase, which cleaves X-proline or X-alanine dipeptide residues in the penultimate position from the NH 2-terminus of polypeptide substrates, including chemokines, neuropeptides and hormones. 4-6 The cysteine-rich domain of DPP4 interacts with the proteins of the extracellular matrix whilst the glycosylation-rich domain interacts with adenosine deaminase and caveolin-1 amongst others. 5,7,8 DPP4 inhibitors (DPP4i) are best known for their role in the treatment of diabetes mellitus due to their ability to deactivate incretins, such as glucose-dependent insulinotropic polypeptide and glucagon-like peptide-1. 9 The rise of DPP4 inhibitors, however, is also accompanied by undesired cardiovascular and dermatologic manifestations. 10-12 More recently, the role of DPP4 and its inhibition in various dermatoses including bullous pemphigoid, psoriasis and mycosis fungoides have been described. In this review, we sought to summarize the role of DPP4 expression, regulation, and inhibition in cutaneous diseases.

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Bullous pemphigoid induced by dipeptidyl peptidase-4 (DPP-4) inhibitors: a pharmacovigilance-pharmacodynamic/pharmacokinetic assessment through an analysis of the vigibase®

Cited by 29 publications

References 65 publications

Adverse event profiles of dipeptidyl peptidase-4 inhibitors: data mining of the public version of the FDA adverse event reporting system

Adverse event profiles of dipeptidyl peptidase-4 inhibitors: data mining of the public version of the FDA adverse event reporting system

Bullous Pemphigoid: Trigger and Predisposing Factors

The role of Dipeptidyl Peptidase‐4 in cutaneous disease

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