Association Between Medication Use and Bullous Pemphigoid

Abstract

IMPORTANCEThe association between the use of medications and the development of bullous pemphigoid (BP) is unclear.OBJECTIVE To assess the associations between previous exposure to certain medications and BP.DATA SOURCES For this systematic review and meta-analysis, PubMed, the Cochrane Central Register of Controlled Trials, and Embase were searched for relevant studies from inception to February 20, 2020.STUDY SELECTION Case-control or cohort studies and randomized clinical trials that examined the odds or risk of BP in patients with previous medication use were included. No geographic or language limitations were imposed. DATA EXTRACTION AND SYNTHESISThe Meta-analysis of Observational Studies in Epidemiology (MOOSE) guideline was followed. The Newcastle-Ottawa Scale was used to evaluate the risk of bias of included observational studies; Cochrane Collaboration's tool was used for randomized clinical trials. Aggregate data were used to conduct a random-effects model meta-analysis if the included studies were sufficiently homogenous. Subgroup analyses were performed for use of various medications of the same category. MAIN OUTCOMES AND MEASURESOdds ratio (OR), hazard ratio, and risk ratio of bullous pemphigoid in association with medication use. RESULTSThis meta-analysis included 13 case-control studies, 1 cohort study, and 1 randomized clinical trial with a total of 285 884 participants. The meta-analysis of case-control studies showed a significant association of BP with previous use of aldosterone antagonists (pooled OR, 1.75; 95% CI, 1.28-2.40), dipeptidyl peptidase 4 inhibitors (pooled OR, 1.92; 95% CI, 1.55-2.38), anticholinergics (pooled OR, 3.12; 95% CI, 1.54-6.33), and dopaminergic medications (pooled OR, 2.03; 95% CI, 1.34-3.05). One cohort study found an increased risk of BP among patients receiving dipeptidyl peptidase 4 inhibitors (hazard ratio, 2.38; 95% CI, 1.16-4.88; P = .02). One trial found a higher occurrence of BP in patients with diabetes receiving linagliptin (0.2% in diabetes group vs 0% in the placebo group). CONCLUSIONS AND RELEVANCEThe findings of this systematic review and meta-analysis suggest that aldosterone antagonists, dipeptidyl peptidase 4 inhibitors, anticholinergics, and dopaminergic medications are associated with BP. These medications should be judiciously prescribed, particularly in high-risk patients who are elderly and have disabling neurologic disorders.

Defining dipeptidyl peptidase‐4 inhibitors‐related bullous pemphigoid: A single‐centre retrospective study

“…16,29,38 It seems very unlikely that metformin is responsible for the disease as BP cases have never been described during this treatment. 9,22 Other oral antidiabetics different from DPP4i have not been either associated to BP. 22,39 Most case-control 21 and pharmacovigilance 35,37 studies corroborate that vildagliptin use has been associated with the greatest risk for development of BP (OR: 2.7-9.28) [22][23][24][25]29,36 (Appendix S2).…”

“…13,14 The association of DPP4i with BP onset has been supported by case reports, [15][16][17][18][19][20] case-control, [21][22][23][24][25][26] cohort studies, 27,28 systematic reviews and meta-analysis. 9,29 Inhibition of DPP4 has several biologic actions that could explain the onset of BP by either modifying the immune response and/or altering the antigenic properties of the epidermal basement membrane zone. 20 Furthermore, it has been demonstrated that the odds of developing BP vary among the different gliptins agents.…”

The association of bullous pemphigoid with dipeptidyl-peptidase 4 inhibitors: a ten-year prospective observational study

“…Furthermore, some of our patients were on medications that have been associated with BP. In the results we examined the percentage of patients who received drugs associated with BP based on metanalysis of Sian-De Liu et al [12]. However, as the patients had been for at least 3 years on these regimens, any possible causal relationship between the drugs and the BP was rejected.…”

GLP-1 Analogs and SGLT2 Inhibitors Do Not Increase Risk of Bullous Pemphigoid

“…Associations between DM drug usage and BP were evaluated using a conditional logistic regression model. Results were adjusted with DM, several neurological diseases and use of aldosterone antagonists, anticholinergics, antipsychotics and dopaminergic drugs that have been associated with increased risk for BP (Liu et al, 2020). Since several new DM drugs were approved for use in Finland during the study period, regarding these drugs we included only cases and controls diagnosed after the approval.…”