Intake of marine n-3 polyunsaturated fatty acids and the risk of rheumatoid arthritis: protocol for a cohort study using data from the Danish Diet, Cancer and Health cohort and Danish health registers.

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory joint disease with multifactorial aetiology. Smoking is a well-established lifestyle risk factor, but diet may also have an impact on the risk of RA. Intake of the major marine n-3 polyunsaturated fatty acids in particular eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been hypothesised to lower the risk of RA due to their anti-inflammatory effects, although based on limited knowledge. Therefore, we aim to investigate the associations between dietary intake of EPA and DHA and the risk of incident RA. METHODS AND ANALYSIS: A cohort study. The follow-up design will be based on data from the Danish Diet, Cancer and Health cohort, which was established between 1993 and 1997. The participants will be followed through record linkage using nationwide registers including the Danish Civil Registration System, the Danish National Patient Registry and the Danish National Prescription Registry using the unique Civil Personal Registration number. Time-to-event analyses will be conducted with RA as the outcome of interest. The participants will be followed from inclusion until date of RA diagnosis, death, emigration or end of follow-up. HRs with 95% CIs obtained using Cox proportional hazard regression models, with age as underlying time scale and adjustment for established and potential risk factors, will be used as measures of association. ETHICS AND DISSEMINATION: The study has been approved by the Data Protection Committee of Northern Jutland, Denmark (2019-87) and the North Denmark Region Committee on Health Research Ethics (N-20190031). Study results will be disseminated through peer-reviewed journals and presentations at international conferences.

Reduction in Upper Limb Joint Surgery Among Rheumatoid Arthritis Patients: An Interrupted Time-Series Analysis Using Danish Health Care Registers.

OBJECTIVE: Joint replacement surgery is a proxy of severe joint damage in rheumatoid arthritis (RA). The aim of this study was to assess the impact of the introduction of biologic disease-modifying antirheumatic drugs (bDMARDs) on the incidence rate (IR) of upper limb joint replacements among newly diagnosed RA patients. METHODS: Using the Danish National Patient Register, patients with incident RA from 1996-2012 were identified. Each patient was matched on age, sex, and municipality, with up to 10 general population controls. The age- and sex-standardized 5-year IR per 1,000 person-years of a composite outcome of any first joint replacement of the finger, wrist, elbow, or shoulder was calculated, and an interrupted time-series analysis was undertaken to investigate trends and changes of the IR in the pre-bDMARD (1996-2001) and the bDMARD eras (2003-2012), with a 1-year lag period in 2002. RESULTS: In total, 18,654 incident patients with RA were identified (mean age 57.6 years, 70.5% women). The IR of joint replacements among patients with RA was stable at 2.46 per 1,000 person-years (95% confidence interval [95% CI] 1.96, 2.96) from 1996 to 2001 but started to decrease from 2003 onwards (-0.08 per 1,000 person-years annually [95% CI -0.20, 0.02]). Compared with patients with RA, the IR among controls in 1996 was 1/17 and increased continuously throughout the study period. CONCLUSION: The IR of upper limb joint replacements started to decrease among patients with RA from 2002 onwards, whereas it increased among controls. Our results suggest an association between the introduction of bDMARDs and a lower need of joint replacements among patients with RA.