Abstract Background/Aims Risk of venous thromboembolism (VTE) is higher in patients with rheumatoid arthritis (RA) compared to the general population; however, whether this risk changes with RA disease duration remains poorly understood. Acknowledging potential heterogeneity in risk by RA duration could support more tailored screening and effective preventive approaches. In a large population-based study, we aimed to characterise the RA-attributable VTE risk in patients with varying disease durations. Methods Adults registered with a general practice from January 1999 to December 2018 were identified from the Royal College of General Practitioners Research (RCGP) and Surveillance Centre (RSC) primary care database. RA patients (diagnosed prior to and during the study period), VTE outcome (as a composite of pulmonary embolism [PE] or deep vein thrombosis [DVT]) and individual PE and DVT outcomes were determined using previously validated algorithms. RA-unaffected controls (UCs) were matched 4:1 with RA patients by current age, sex, calendar time, and years since practice registration using nearest neighbour matching with replacement. Absolute VTE, PE and DVT rates over 20 years were compared in RA patients versus matched UC across four subgroups defined by disease duration (0-2, 2-5, 5-10 and ≥10 years since diagnosis). Across the same subgroups, relative risks over the same period were estimated using Cox proportional hazards models adjusted for sociodemographic and clinical features and established VTE risk factors (body-mass index [BMI], smoking status, alcohol use, evidence of reduced mobility, thrombophilia, fracture of the lower limb and family history of VTE). Results 117,050 individuals were included, of whom 93,640 were UCs and 23,410 were RA patients. Among those with RA, 63.9% were included at or within two years of diagnosis, 7.8% within two to five years of diagnosis, 9.8% within five to ten years of diagnosis, and 18.5% more than 10 years after diagnosis. Average study follow-up for the primary outcome (VTE) was 8.2 years (standard deviation [SD]=6.6 years). RA patients (mean age 59.0, SD 15.5; 28.9% male [n = 6776]; mean BMI 27.1, SD 5.6) were similar to matched UCs in clinical characteristics. Unadjusted VTE events rates were consistently higher in RA patients compared to UCs across all subgroups. Relative risk of VTE was similarly increased in RA patients compared to the general population regardless of the time elapsed since RA diagnosis (adjusted hazard ratios [aHR] range: 1.49-1.63, all p < 0.001). The results obtained when PE (aHR range 1.46-2.02, all p < 0.001) and DVT (aHR range 1.43-1.89, all p < 0.001) were analysed separately were similar to those observed in the composite outcome. Conclusion Healthcare professionals should recognize that individuals with RA face a consistently elevated VTE risk compared to the general population, irrespective of disease duration. This highlights the need for vigilant monitoring and assessment of VTE risk factors even in early-stage cases. Disclosure J. Galloway: Honoraria; JG has received honoraria from Abbvie, Biovitrum, BMS, Celgene, Chugai, Gilead, Janssen, Lilly, Novartis, Pfizer, Roche, Sanofi, Sobi and UC. V. Basey: Corporate appointments; Pfizer employee. S. Rana: Corporate appointments; Pfizer employee. S. de Lusignan: Grants/research support; SdeL has received funding through his universities from Eli Lilly, GSK, Astra Zeneca, MSD, Sanofi, Seqirus, Takeda and Moderna. Other; Director of the RCGP RSC. M.H. Buch: Consultancies; M.H.B. has provided expert advice and received/paid to employer consultant fees from AbbVie, Eli Lilly, EMD serono, Gilead, Pfizer and Sanofi. Grants/research support; M.H.B. has received research grants paid to her employer from Gilead Ltd, Pfizer Ltd, Roche and UCB.
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