Abstract

Abstract Background/Aims Risk of venous thromboembolism (VTE) is increased in people with rheumatoid arthritis (RA) when compared to the general population, but the variation of this risk among patients is not well understood. Acknowledging the heterogeneity in RA-attributable VTE risk could support tailoring of treatment plans and screening protocols based on an individual’s specific risk profile. In a large population-based study, we aimed to evaluate for variation in RA-attributable VTE risk by age, sex and body-mass index (BMI). 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 and VTE outcome (composite of pulmonary embolism and deep vein thrombosis) 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 rates over 20 years were compared in RA patients versus matched UCs, overall and by age category (18-49, 50-69, ≥70), sex, and BMI category (BMI <25, 25-29.9, ≥30). Across the same subgroups, relative VTE risk over the same period was estimated using Cox proportional hazards models adjusted for sociodemographic and clinical features and established VTE risk factors (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 23,410 were RA patients and 93,640 were UCs. Average follow-up 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 overall and across all subgroups (overall rates RA: 442.4 per 100,000 person-years [py], 95% confidence interval [CI]: 413.0, 473.2; UC: 262.2 per 100,000 py, 95%CI: 251.9, 273.9); subgroup rates). Similarly, overall relative VTE risk was 46% higher in people with RA compared to UCs (adjusted hazard ratio [aHR]= 1.46, 95%CI: 1.36, 1.56; p < 0.001), and was consistently higher across age-, sex- and BMI-defined subgroups (aHR range: 1.34-2.13, all p < 0.001). Although relative risk was highest in RA patients under 50 years (aHR= 2.13, 95%CI: 1.62-2.79; p < 0.001), this patient subgroup had the lowest absolute risk of VTE (approximately 2.2- and 3.4-fold lower than that observed in those aged 50-69 and ≥70, respectively). Conclusion Clinicians should be aware that risk of VTE is consistently higher in people with RA compared to the general population, regardless of age, sex and BMI. Findings suggest close monitoring and assessment of VTE risk factors is required even in younger individuals with RA. 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. M. Mclean: 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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