Bullous Pemphigoid and Dipeptidyl Peptidase 4 Inhibitors: A Disproportionality Analysis Based on the Japanese Adverse Drug Event Report Database

Arai, Masanori; Shirakawa, Jun; Konishi, Hiromi; Sagawa, Noriko; Terauchi, Yasuo

doi:10.2337/dc18-0210

Cited by 62 publications

(93 citation statements)

References 5 publications

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“…Although disproportionality analyses have been validated and used in pharmacoepidemiological studies, this study design is different to that of case–control studies, and as such reporting odds ratios (ROR) of the former should not be combined with odds ratio (OR) of the latter. Furthermore, database studies are susceptible to underreporting of adverse events given that data are reported spontaneously and not routinely, lack of control data, and selection bias . To address the above limitations, we performed unadjusted and adjusted meta‐analyses based on case–control data.…”

Section: Discussionmentioning

confidence: 99%

Dipeptidyl peptidase‐4 inhibitors and bullous pemphigoid: A systematic review and adjusted meta‐analysis

2019

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Background/Objective There have been a number of case reports and small clinical series reporting the potential association between dipeptidyl peptidase‐4 inhibitors (DPPIs) for diabetes and the onset of bullous pemphigoid (BP). The aim of this study was to assess the association between DPPI use and BP, and whether this varied according to DPPI type. Methods We performed a systematic review and meta‐analysis according to PRISMA guidelines. We identified five studies with cases and controls. We performed unadjusted and adjusted meta‐analyses to assess the potential association. Results Adjusted meta‐analysis revealed significant association between DPPI use and BP (OR 2.13, 95% CI 1.59–2.86, I2 = 46%, P < 0.00001). This association was stronger between vildagliptin and BP (OR 5.08, 95% CI 1.70–15.19, P = 0.004) compared to linagliptin (OR 2.87, 95%CI 1.06–7.79, P = 0.04), and no association was found between sitagliptin and BP (OR 1.29, 95%CI 0.79–2.08, P = 0.31). Subgroup analysis demonstrated that the association between DPPI use and BP remained significant in males (OR 2.35, 95% CI 1.46–3.78, P = 0.0005) and females (OR 1.88, 95%CI 1.10–3.22, P = 0.02). Conclusions Limitations were that studies reviewed were retrospective by design which are susceptible to bias and lack of randomisation. Our adjusted analysis supports a significant association between DPPI use and onset of bullous pemphigoid. Vildagliptin had the highest odds of BP. These findings have clinical implications for dermatologists and the management of patients with diabetes and being treated with DPPI agents.

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Section: Discussionmentioning

confidence: 99%

Dipeptidyl peptidase‐4 inhibitors and bullous pemphigoid: A systematic review and adjusted meta‐analysis

2019

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“…5,6 The ROR was especially high for vildagliptin relative to other DPP4-I. 8,14 Further studies are needed to clarify the synergistic effect of the DPP4-I and metformin combination on BP onset. The ROR of other diabetic drugs, especially metformin, listed as causative drugs for pemphigoid may be greatly affected by concomitant use with DPP4-I.…”

Section: Discussionmentioning

confidence: 99%

“…1 It has been reported that the onset of BP may be associated with the use of various drugs, such as antibiotics, antihypertensive drugs, anti-inflammatory drugs, diuretics, biopharmaceuticals, antirheumatic drugs and vaccines. [3][4][5][6][7] Most recently, an inhomogeneity analysis of BP associated with the use of DPP4-I based on the Japanese Adverse Drug Event Report database (JADER) 8 was also reported. [3][4][5][6][7] Most recently, an inhomogeneity analysis of BP associated with the use of DPP4-I based on the Japanese Adverse Drug Event Report database (JADER) 8 was also reported.…”

Section: Introductionmentioning

confidence: 99%

Analysis of patients with drug‐induced pemphigoid using the Japanese Adverse Drug Event Report database

Tanaka

Ishii

2018

The Journal of Dermatology

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To clarify the incidence of drug‐induced pemphigoid in Japan, we conducted a database search and analysis using the Japanese Adverse Drug Event Report database (JADER). Among the cases recorded in JADER between April 2004 and November 2017, we targeted “pemphigoid” and analyzed the patients’ backgrounds, drug involvement, time of pemphigoid onset, outcomes and year reported. For cases where three or more drugs were reportedly involved, the signal index was calculated using the reporting odds ratio (ROR) method. The total number of reported pemphigoid cases was 769. Males accounted for 58% (446 cases) and patients over the age of 60 years accounted for 82% (630 cases). The most frequently reported causative drug was vildagliptin (288 cases), followed in order by sitagliptin phosphate hydrate (102 cases), teneligliptin hydrobromide hydrate (86 cases), linagliptin (64 cases) and furosemide (46 cases). For the 27 causative drugs, the safety signal was detected by the ROR method. The median time to onset tended to be long for these drugs. For vildagliptin with the largest reported number, the value was 508 days (range, 2–1871). Analysis of outcomes demonstrated recovery or improvement in 66.3% of cases. Analysis of the years in which reports had been published revealed that the number of pemphigoid cases has increased rapidly in recent years. Our survey was able to reveal useful data on the incidence of drug‐induced pemphigoid. We expect that these results will aid the early detection and treatment of this condition.

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“…The reporting odds ratio (ROR) of the Japanese adverse drug event report for alogliptin is very low (8.6), in contrast to those for vildagliptin (105.3) . The latter is confirmed to induce BP . Moreover, although the erythema/urticaria in terms of BPDAI was mild, anti‐BP180 NC16a antibody was detected, which indicates the classic BP type but not gliptin‐related BP .…”

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confidence: 97%

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confidence: 97%

Alogliptin‐induced bullous pemphigoid associated with HLA‐DQB1*03:01: a case report

et al. 2019

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Bullous Pemphigoid and Dipeptidyl Peptidase 4 Inhibitors: A Disproportionality Analysis Based on the Japanese Adverse Drug Event Report Database

Cited by 62 publications

References 5 publications

Dipeptidyl peptidase‐4 inhibitors and bullous pemphigoid: A systematic review and adjusted meta‐analysis

Dipeptidyl peptidase‐4 inhibitors and bullous pemphigoid: A systematic review and adjusted meta‐analysis

Analysis of patients with drug‐induced pemphigoid using the Japanese Adverse Drug Event Report database

Alogliptin‐induced bullous pemphigoid associated with HLA‐DQB1*03:01: a case report

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