Antonios Douros1,2,3, Julie Rouette4, Hui Yin1, Oriana Hoi Yun Yu1,5, Kristian B Filion1,2,4, Laurent Azoulay6,4,7. 1. Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Canada. 2. Department of Medicine, McGill University, Montreal, Canada. 3. Institute of Clinical Pharmacology and Toxicology, Charité-Universitätsmedizin Berlin, Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany. 4. Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Canada. 5. Division of Endocrinology, Jewish General Hospital, Montreal, Canada. 6. Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Canada laurent.azoulay@mcgill.ca. 7. Gerald Bronfman Department of Oncology, McGill University, Montreal, Canada.
Abstract
OBJECTIVE: There are uncertainties regarding the association between dipeptidyl peptidase 4 (DPP-4) inhibitors and bullous pemphigoid (BP), a potentially severe autoimmune skin disease. Thus, we conducted a population-based study to determine whether use of DPP-4 inhibitors, when compared with other second- to third-line antidiabetic drugs, is associated with an increased risk of BP in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Using the U.K. Clinical Practice Research Datalink, we conducted a cohort study among 168,774 patients initiating antidiabetic drugs between January 2007 and March 2018. Using time-dependent Cox proportional hazards models, we estimated adjusted hazard ratios (HRs) with 95% CIs of incident BP associated with current use of DPP-4 inhibitors, compared with current use of other second- to third-line antidiabetic drugs. We also conducted a propensity score-matched analysis to assess the impact of residual confounding. RESULTS: During 711,311 person-years of follow-up, 150 patients were newly diagnosed with BP (crude incidence rate, 21.1 per 100,000 person-years). Current use of DPP-4 inhibitors was associated with an increased risk of BP (47.3 vs. 20.0 per 100,000 person-years; HR 2.21 [95% CI 1.45-3.38]). HRs gradually increased with longer durations of use, reaching a peak after 20 months (HR 3.60 [95% CI 2.11-6.16]). Similar results were obtained in the propensity score-matched analysis (HR 2.40 [95% CI 1.13-4.66]). CONCLUSIONS: In this large population-based study, use of DPP-4 inhibitors was associated with an at least doubling of the risk of BP in patients with type 2 diabetes, albeit the absolute risk was low.
OBJECTIVE: There are uncertainties regarding the association between dipeptidyl peptidase 4 (DPP-4) inhibitors and bullous pemphigoid (BP), a potentially severe autoimmune skin disease. Thus, we conducted a population-based study to determine whether use of DPP-4 inhibitors, when compared with other second- to third-line antidiabetic drugs, is associated with an increased risk of BP in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS: Using the U.K. Clinical Practice Research Datalink, we conducted a cohort study among 168,774 patients initiating antidiabetic drugs between January 2007 and March 2018. Using time-dependent Cox proportional hazards models, we estimated adjusted hazard ratios (HRs) with 95% CIs of incident BP associated with current use of DPP-4 inhibitors, compared with current use of other second- to third-line antidiabetic drugs. We also conducted a propensity score-matched analysis to assess the impact of residual confounding. RESULTS: During 711,311 person-years of follow-up, 150 patients were newly diagnosed with BP (crude incidence rate, 21.1 per 100,000 person-years). Current use of DPP-4 inhibitors was associated with an increased risk of BP (47.3 vs. 20.0 per 100,000 person-years; HR 2.21 [95% CI 1.45-3.38]). HRs gradually increased with longer durations of use, reaching a peak after 20 months (HR 3.60 [95% CI 2.11-6.16]). Similar results were obtained in the propensity score-matched analysis (HR 2.40 [95% CI 1.13-4.66]). CONCLUSIONS: In this large population-based study, use of DPP-4 inhibitors was associated with an at least doubling of the risk of BP in patients with type 2 diabetes, albeit the absolute risk was low.
Authors: Monica S M Persson; Karen E Harman; Yana Vinogradova; Sinead M Langan; Julia Hippisley-Cox; Kim S Thomas; Sonia Gran Journal: BMJ Open Date: 2020-07-14 Impact factor: 2.692
Authors: Karim Chouchane; Giovanni Di Zenzo; Dario Pitocco; Laura Calabrese; Clara De Simone Journal: J Transl Med Date: 2021-12-20 Impact factor: 5.531