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Spondyloarthritis in first-degree relatives and spouses of patients with inflammatory bowel disease: A nationwide population-based cohort study from Sweden
Örebro University, School of Medical Sciences.
Population Health Sciences, Bristol Medical School, University of Bristol, United Kingdom; Medical Research Council Integrative Epidemiology Unit, University of Bristol, Bristol, United Kingdom; Clinical Epidemiology and Biostatistics, School of Medical Sciences, Faculty of Medicine and Health, Örebro University Hospital, Örebro, Sweden.
Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.
Örebro University, School of Medical Sciences. Örebro University Hospital. Clinical Epidemiology Division, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden; Department of Gastroenterology, Faculty of Medicine and Health, Örebro University, Örebro, Sweden.ORCID iD: 0000-0002-1046-383x
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2024 (English)In: Journal of Crohn's & Colitis, ISSN 1873-9946, E-ISSN 1876-4479, Vol. 18, no 9, p. 1371-1380Article in journal (Refereed) Published
Abstract [en]

BACKGROUND AND AIMS: Register-based research suggests a shared pathophysiology between inflammatory bowel disease [IBD] and spondyloarthritis [SpA], but the role of familial [genetic and environmental] factors in this shared susceptibility is largely unknown. We compared the risk of SpA in first-degree relatives [FDRs] and spouses of IBD patients with FDRs and spouses of matched population-based reference individuals.

METHODS: We identified 147,080 FDRs and 25,945 spouses of patients with incident IBD [N=39,203] during 2006-2016 and 1,453,429 FDRs and 258,098 spouses of matched reference individuals [N=390,490], by linking nationwide Swedish registers and gastrointestinal biopsy data. Study participants were followed 1987-2017. Cox regression was used to estimate hazard ratios [HRs] of SpA.

RESULTS: During follow-up, 2,430 FDRs of IBD patients [6.5/10,000 person-years] and 17,761 FDRs of reference individuals [4.8/10,000 person-years] were diagnosed with SpA, corresponding to an HR of 1.35 [95%CI:1.29,1.41]. In subgroup analyses, the increased risk of SpA was most pronounced in FDRs of Crohn's disease patients [HR=1.44; 95%CI:1.34,1.56] and of IBD patients aged <18 years at diagnosis [HR=1.46; 95%CI: 1.27,1.68]. IBD patient's spouses also had a higher SpA rate than reference individuals' spouses, but the difference was less pronounced [4.3 vs. 3.5/10,000 person-years; HR=1.22; 95%CI:1.09,1.37]. No subgroup-specific risk pattern was identified among spouses.

CONCLUSIONS: The observed shared familial risks between IBD and SpA support shared genetic factors in their pathogenesis. However, spouses of IBD patients were also at increased risk for SpA, reflecting the influence of environmental exposures or similarities in health-seeking patterns.

Place, publisher, year, edition, pages
Oxford University Press, 2024. Vol. 18, no 9, p. 1371-1380
Keywords [en]
epidemiology, first-degree relatives, inflammatory bowel diseases, spondyloarthritis, spouses, ulcerative colitis
National Category
Gastroenterology and Hepatology
Identifiers
URN: urn:nbn:se:oru:diva-112556DOI: 10.1093/ecco-jcc/jjae041ISI: 001198352900001PubMedID: 38518097Scopus ID: 2-s2.0-85203054672OAI: oai:DiVA.org:oru-112556DiVA, id: diva2:1846703
Funder
EU, Horizon 2020, 754285Region Örebro County, OLL-936004; OLL-890291; OLL-790011; OLL- 723021Swedish Research Council, 2020-02021
Note

Funding agency:

Danish National Research Foundation DNRF148

Available from: 2024-03-25 Created: 2024-03-25 Last updated: 2025-02-11Bibliographically approved
In thesis
1. Impact of age and inflammation on extraintestinal manifestations of inflammatory bowel disease
Open this publication in new window or tab >>Impact of age and inflammation on extraintestinal manifestations of inflammatory bowel disease
2024 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, is often complicated by extraintestinal manifestations (EIMs) that affect organs beyond the gastrointestinal tract. The EIMs can significantly impair quality of life and complicate disease management in patients with IBD. As the population ages, understanding the interplay between age, chronic inflammation, and EIMs becomes increasingly important for optimizing patient care and outcomes. Thus, the overall aim of the thesis was to assess the impact of age and inflammation on EIM of IBD.

We conducted all studies using Swedish national registers. To evaluate the accuracy of the National patient register (NPR), we compared International classification of diseases (ICD) coded IBD data with clinical records from 1403 IBD patients. For investigating spondyloarthritis (SpA) comorbidity, a cohort of 39,203 IBD patients diagnosed between 2006-2016 and 390,490 matched reference individuals were analyzed. The familial risk of SpA was assessed among 147,080 first-degree relatives (FDRs) and 25,945 spouses of IBD patients. The influence of colectomy on SpA and other EIMs was studied in 3246 ulcerative colitis patients, comparing EIM rates before and after surgery.

The NPR showed high positive predictive values (PPVs) for Crohn's disease (97%) and ulcerative colitis (98%) but a low PPV for IBD-unclassified (8%). Crohn's disease location and behaviour had variable PPVs, indicating frequent misclassification. A high PPV (95%) was observed for age at diagnosis of IBD. Patients with IBD had significantly higher relative risk estimates of SpA both before (odds ratio [OR]: 3.48) and after (hazard ratio [HR]: 7.15) IBD diagnosis compared to the general population. FDRs of IBD patients exhibited a higher risk of SpA (HR: 1.35). Spouses also had an elevated SpA risk, suggesting environmental influences. The highest risks were observed in Crohn's disease and pediatric-onset IBD. Post-colectomy, patients with ulcerative colitis experienced increased EIM rates (rate ratios [RR]: 1.83). In addition, de novo EIMs frequently occurred in patients with no history of EIMs before colectomy.

The NPR is a reliable source for subtype of IBD, although improvements are needed for phenotypic accuracy. IBD significantly increases the risk of SpA. The elevated SpA risk among FDRs and spouses points to shared genetic and environmental factors. Colectomyin patients with ulcerative colitis does not mitigate the risk of EIMs, indicating a need for continued monitoring and management post-surgery. This thesis underscores the importance of comprehensive care approaches that address both gastrointestinal and extraintestinal challenges in IBD.

Place, publisher, year, edition, pages
Örebro: Örebro University, 2024. p. 99
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 295
Keywords
inflammatory bowel disease, Crohn's disease, ulcerative colitis, ageing, spondyloarthritis, extraintestinal manifestations, colectomy, epidemiology
National Category
General Practice
Identifiers
urn:nbn:se:oru:diva-113987 (URN)9789175295671 (ISBN)9789175295688 (ISBN)
Public defence
2024-09-20, Örebro universitet, Campus USÖ, Tidefeltsalen, Södra Grev Rosengatan 32, Örebro, 09:00 (English)
Opponent
Supervisors
Available from: 2024-05-30 Created: 2024-05-30 Last updated: 2024-08-27Bibliographically approved

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Shrestha, SaritaEriksson, CarlSchoultz, IdaMontgomery, ScottHalfvarson, Jonas

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