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P688 Crohn's disease patients with a concordant family history are diagnosed earlier and are at increased risk for complicated disease

Borren N.*1,2, Conway G.1, Garber J.1,3, Khalili H.1,3, Yajnik V.1,3, Xavier R.1,3, Ananthakrishnan A.1,3

1Massachusetts General Hospital, Department of Gastroenterology, Boston, United States 2University of Groningen, Groningen, Netherlands 3Harvard Medical School, Boston, United States

Background

Family history is the strongest risk factor for developing Crohn's disease (CD) or ulcerative colitis (UC). However, whether familial Inflammatory Bowel Disease (IBD) differs from sporadic IBD in its natural history has not been well defined. We investigated whether the proximity of relationship with the affected relative and concordance for type of IBD modifies the effect of family history on the phenotype and severity of IBD.

Methods

This study included patients with a confirmed diagnosis of IBD enrolled in a prospective patient registry at a tertiary referral hospital from January 2005 to August 2016. Family history of CD or UC was assessed by a questionnaire ascertaining presence of disease in a 1st degree (parent, child, sibling), 2nd degree (grandparent, uncle, aunt), or a distant relative (familial IBD). IBD occurring in the absence of such a history was termed sporadic IBD. Our primary outcomes were disease phenotype according to the Montreal classification and severity measured by need for immunomodulator, biologic, or surgical therapy. Adjusted regression models were used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI).

Results

Our study included 2,136 patients with IBD (1,197 CD, 939 UC) with a mean age of 41 years; just over half were women (52%). Just under one-third (32%) of cases were familial IBD (17% 1st degree relative, 21% 2nd degree relative) while the remainder were sporadic IBD. Familial IBD was diagnosed at an earlier age than sporadic IBD, both in CD (26 vs. 28 years, p=0.0006) and UC (29 vs. 32 years, p=0.01). This effect was more striking in those where the family history was concordant for type of IBD (p=0.0005) than when it was discordant (p=0.06). Among CD patients, a positive family history for CD was associated with an increased risk for complicated disease (B2/B3 phenotype or perianal involvement) in the presence of an affected family member (OR 1.48, 95% CI 1.07–2.03). However, this effect was significant only if the affected member was a 1st degree relative (OR 1.82, 95% CI 1.19– 2.78) (Table 1).

Figure 1

Among 1st degree relatives, the association with complicated CD was more striking in the presence of CD in a sibling (p=0.008). A family history was not associated with need for immunosuppressive therapy or surgery in either CD or UC.

Conclusion

A family history of CD in 1st degree relatives was associated with complicated CD. Family history discordant for type of IBD or in more distant relatives did not influence disease phenotype or natural history in the affected patient.