Antonios Douros1,2,3, Devin Abrahami1,2, Hui Yin1, Oriana Hoi Yun Yu1,4, Christel Renoux1,2,5, Marie Hudson1,6,7, Laurent Azoulay1,2,8. 1. From the Centre for Clinical Epidemiology, Lady Davis Institute, Jewish General Hospital, Montreal, Canada. 2. Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montreal, Canada. 3. Institute of Clinical Pharmacology and Toxicology, Charité - Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany. 4. Division of Endocrinology, Jewish General Hospital, Montreal, Canada. 5. Department of Neurology and Neurosurgery, McGill University, Montreal, Canada. 6. Division of Rheumatology, Jewish General Hospital, Montreal, Canada. 7. Department of Medicine, McGill University, Montréal, Canada. 8. Gerald Bronfman Department of Oncology, McGill University, Montreal, Canada.
Abstract
BACKGROUND: Case reports have suggested a link between dipeptidyl peptidase-4 (DPP-4) inhibitors, antidiabetic drugs used as second- to third-line treatments, and incidence of rheumatoid arthritis. Because the DPP-4 enzyme is involved in several immunologic processes and possibly in the pathophysiology of rheumatoid arthritis, further research is warranted. This population-based study aimed to determine whether use of DPP-4 inhibitors is associated with incidence of rheumatoid arthritis. METHODS: Using the United Kingdom Clinical Practice Research Datalink, we conducted a cohort study among 144,603 patients with type 2 diabetes initiating antidiabetic drugs between 2007 and 2016. We estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for incident rheumatoid arthritis using time-dependent Cox proportional hazards models, comparing use of DPP-4 inhibitors with use of other antidiabetic drugs. We imposed a 6-month exposure lag period for latency and diagnostic delays. Secondary analyses included assessment of the duration-response relation and comparison with other second-line antidiabetic drugs, among others. RESULTS: During 567,169 person-years of follow-up, 464 patients were newly diagnosed with rheumatoid arthritis (crude incidence rate: 82 per 100,000/year). Compared with use of other antidiabetic drugs, use of DPP-4 inhibitors was not associated with an increased risk of rheumatoid arthritis (82 vs. 79 per 100,000/year; HR = 1.0; 95% CI = 0.8, 1.3), with no evidence of duration-response relation. The results did not change after using second-line antidiabetic drugs as the comparator group. CONCLUSIONS: In this large population-based study, use of DPP-4 inhibitors was not associated with an increased risk of incident rheumatoid arthritis.
BACKGROUND: Case reports have suggested a link between dipeptidyl peptidase-4 (DPP-4) inhibitors, antidiabetic drugs used as second- to third-line treatments, and incidence of rheumatoid arthritis. Because the DPP-4 enzyme is involved in several immunologic processes and possibly in the pathophysiology of rheumatoid arthritis, further research is warranted. This population-based study aimed to determine whether use of DPP-4 inhibitors is associated with incidence of rheumatoid arthritis. METHODS: Using the United Kingdom Clinical Practice Research Datalink, we conducted a cohort study among 144,603 patients with type 2 diabetes initiating antidiabetic drugs between 2007 and 2016. We estimated hazard ratios (HRs) with 95% confidence intervals (CIs) for incident rheumatoid arthritis using time-dependent Cox proportional hazards models, comparing use of DPP-4 inhibitors with use of other antidiabetic drugs. We imposed a 6-month exposure lag period for latency and diagnostic delays. Secondary analyses included assessment of the duration-response relation and comparison with other second-line antidiabetic drugs, among others. RESULTS: During 567,169 person-years of follow-up, 464 patients were newly diagnosed with rheumatoid arthritis (crude incidence rate: 82 per 100,000/year). Compared with use of other antidiabetic drugs, use of DPP-4 inhibitors was not associated with an increased risk of rheumatoid arthritis (82 vs. 79 per 100,000/year; HR = 1.0; 95% CI = 0.8, 1.3), with no evidence of duration-response relation. The results did not change after using second-line antidiabetic drugs as the comparator group. CONCLUSIONS: In this large population-based study, use of DPP-4 inhibitors was not associated with an increased risk of incident rheumatoid arthritis.
Authors: Til Stürmer; Tiansheng Wang; Yvonne M Golightly; Alex Keil; Jennifer L Lund; Michele Jonsson Funk Journal: Rheumatology (Oxford) Date: 2020-01-01 Impact factor: 7.580