Objective: to investigate the bidirectional prospective association between inflammatory bowel disease (IBD) and rheumatoid arthritis (RA) in a large-scale, long-term follow-up, population-based cohort.

Methods: Participants free of any cancer at baseline were included and divided into two prospective cohorts: baseline IBD and incident RA cohort (cohort 1), and baseline RA and incident IBD cohort (cohort 2), respectively. The primary outcome was incident RA in cohort 1 and incident IBD, including ulcerative colitis (UC) and Crohn's disease (CD) in cohort 2, separately. Cox proportional hazard regression models were used to investigate the bidirectional relationship between RA and IBD.

Results: Overall, 449 662 and 450 534 participants were included in cohort 1 and cohort 2, with 5,015/5,887 prevalent IBD/RA cases at baseline, respectively. During a median of 14.3/14.6-year follow-up, 6,001(1.3%)/2,988(0.7%) cases of RA and IBD were identified in each cohort. Compared with non-IBD, IBD patients (HR = 1.44, 95% CI: 1.15-1.79) showed a significantly higher risk of incident RA, particularly in UC patients (HR = 1.36, 95% CI: 1.06-1.75) after multivariable adjustment. Similarly, RA patients had a 1.65-fold higher risk (95% CI: 1.31-2.09) of incident IBD, with a 60% and 65% excess risk of developing UC (HR = 1.60, 95% CI: 1.20-2. 13) and CD (HR = 1.65, 95% CI: 1.12-2. 42), respectively. Further sensitivity analysis and subgroup analysis indicated similar results.

Conclusions: IBD is associated with an increased risk of RA, and vice versa. Further studies are warranted to confirm the findings and elucidate the underlying biological mechanisms.