ACARBOSE DECREASES THE RISK OF RHEUMATOID ARTHRITIS IN DIABETIC PATIENTS AND ATTENUATES THE INCIDENCE AND SEVERITY OF COLLAGEN-INDUCED ARTHRITIS IN MICE: POPULATION-BASED CASE-CONTROL STUDY AND ANIMAL STUDY

Background: Acarbose was found to decrease inflammatory parameters in diabetic mellitus (DM) patients. However, whether acarbose reduces the risk of rheumatoid arthritis (RA) and collagen-induced arthritis (CIA) with immunomodulatory effects has not been established. Objectives: To examine the influence of acarbose on RA risk in DM patients and on the incidence and severity of CIA in mice. Methods: In a nationwide, matched case–control study, we identified 723 incident RA cases and selected 7,230 age-, sex- and RA diagnosis date–matched controls from all newly treated DM patients. The effect of acarbose was tested by conditional logistic regression analyses adjusting for potential confounders. In a CIA mouse study, acarbose was orally administered from day -7 to 38 after type II collagen (CII) immunization and arthritis activity was evaluated by arthritic score and the joint histopathology. Levels of cytokines and anti-CII antibodies were detected by ELISA. The expansion of CII-specific lymphocytes in the lymph nodes were determined by [H] thymidine incorporation assay. Results: Use of acarbose >16950 mg per year was associated with a lower RA risk (odds ratio [OR] 0.60; 95% CI, 0.41–0.89). Acarbose at a dose of 500 mg/kg/day attenuated arthritis incidence, severity and proinflammatory cytokines expressions including TNF-α, IL-6 and IL-17A in paw tissues of CIA mice. Acarbose further decreased the production of anti-CII-IgG, and IL-17A and IFN-g by collagen-reactive lymph node cells in CIA mice. However, the expression of IL-10 was significantly increased in acarbose-treated mice compared with the control mice. Table 1. Univariate and multivariate adjusted odds ratios with 95% confidence intervals for rheumatoid arthritis risk associated with variables in newly treated diabetes patients VariableUnivariateMultivariate Model 1Model 2 Acarbose  Not useReferenceReferenceReference  Use0.79 (0.61–1.03)*  ≤16950 mg1.34 (0.97–1.85)–1.00 (0.72–1.39)  >16950 mg0.94 (0.64–1.37)–0.60 (0.41–0.89) Sulphonylurea and meglitinide1.34 (1.15–1.55)1.07 (0.91–1.25)1.08 (0.92–1.26) Metformin1.26 (1.07–1.47)1.27 (1.08–1.50)1.26 (1.06–1.49) Thiazolidinediones1.29 (1.00–1.65)0.96 (0.74–1.25)0.96 (0.74–1.24) Insulin2.31 (1.70–3.14)0.64 (0.46–0.89)0.62 (0.45–0.87) Statin1.06 (0.90–1.26)1.14 (0.96–1.35)1.14 (0.96–1.36) DM duration, year1.32 (1.28–1.37)1.22 (1.18–1.26)1.22 (1.18–1.27) DM end-organ disease (ICD9-CM: 250.1–9)9.74 (8.38–11.31)2.66 (2.22–3.18)2.67 (2.23–3.19) Charlson comorbidity index1.34 (1.32–1.36)1.28 (1.26–1.31)1.28 (1.26–1.31) Periodontitis1.03 (0.85–1.25)1.11 (0.91–1.35)1.11 (0.91–1.35) *P=0.079, p=0.047. Figure 1 Conclusions: The use of acarbose decreased the risk of RA in DM patients and the incidence of CIA in mice. Acarbose also attenuated the severity of CIA with anti-inflammatory and immunomodulatory effects. References: 1. Derosa G, Maffioli P, Ferrari I, et al. Acarbose actions on insulin resistance and inflammatory parameters during an oral fat load. Eur J Pharmacol 2011;651:240-50. Disclosure of Interest: None declared DOI: 10.1136/annrheumdis-2015-eular.2652Citation: Annals of the Rheumatic Diseases, volume 74, supplement 2, year 2015, page 735Session: Rheumatoid arthritis - non biologic treatment and small molecules (Poster Presentations )