Sarita Shrestha [1], Judith S Brand [2,3,4], Mehdi Osooli [5], Carl Eriksson [5,6], Ida Schoultz [1], Johan Askling [5,7], Jonas F Ludvigsson [8,9,10], Tine Jess [11], Scott Montgomery [5,12], Ola Olen [5,13,14], Jonas Halfvarson [6]

Affiliates

1School of Medical Sciences, Faculty of Medicine and Health, Örebro University, Örebro, Sweden 2Population Health Sciences, Bristol Medical School, University of Bristol, United Kingdom 3Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom 4Clinical Epidemiology and Biostatistics, School of Medical Sciences, Örebro University Hospital, Örebro, Sweden 5Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden 6Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden 7Rheumatology, Theme Inflammation and Ageing, Karolinska University Hospital, Stockholm, Sweden 8Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden 9Department of Pediatrics, Orebro University Hospital, Orebro, Sweden 10Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA 11Center for Molecular Prediction of Inflammatory Bowel Disease (PREDICT), Department of Clinical Medicine, Aalborg University, Copenhagen, Denmark; Department of Gastroenterology & Hepatology, Aalborg University Hospital, Aalborg, Denmark. 12Department of Epidemiology and Public Health, University College London, London, United Kingdom 13Department of Clinical Science and Education Södersjukhuset, Karolinska Institutet, Stockholm, Sweden 14Sachs' Children and Youth Hospital, Stockholm South General Hospital, Stockholm, Sweden

Abstract

Aim
Register-based research suggests a shared pathophysiology between inflammatory bowel disease [IBD] and spondyloarthritis [SpA], but little is known about the role of familial [genetic and environmental] factors in this shared susceptibility. To explore the impact of shared familial risk between IBD and spondyloarthritis (SpA), by providing risk estimates for SpA in FDRs and spouses to index IBD patients compared with their corresponding reference individuals from the general population.

Methods
We identified index patients with IBD and up to 10 matched reference individuals for each of the patient. Information on FDRs of index patients with IBD vs their reference individuals were obtained from the Multi-generation Register and data on spouses from the Total Population Register. We used Cox regression to estimate associations between the exposure (being an FDR/ spouse of a IBD index patient) and outcome (diagnosis of SpA) using attained age as underlying time scale. We repeated all analyses using time since study entry of the index individual (index date).

Results
During the follow-up period (median, 48.7 years), 2,338 FDRs to IBD patients and 17,200 FDRs to their reference individuals developed SpA. FDRs to IBD patients were at an increased lifetime risk of SpA compared with their reference individuals (HR = 1.34; 95%CI:1.29-1.40) and as were spouses. During the follow-up period (median, 5.5 years), 766 FDRs to IBD patients and 5,427 FDRs to their reference individuals were diagnosed with incident SpA. Compared to reference population, FDRs to IBD patients were at an increased risk of incident SpA [HR of 1.41 (95% CI: 1.31-1.52)] but spouses were not at risk of incident SpA [HR of 1.17 (95%CI: 0.95-1.44)] after the index date.

Conclusions
We found an increased risk of SpA in FDRs to IBD patients, showing evidence of shared susceptibility between IBD and SpA. The degree of shared susceptibility between IBD and SpA seemed to differ across age-groups and was less pronounced in FDRs to patients aged >60 years at diagnosis of IBD. Exposures during adulthood seemed less relevant since risk estimates of SpA were only marginally increased in spouses to IBD patients compared with their reference population.