Women with high circulating levels of interleukin-6 and high-sensitivity C-reactive protein were at significantly greater risk of inflammatory bowel disease (IBD) compared with those testing in the lowest quintiles, according to a prospective nested case-control study.
The findings point to a preclinical state in IBD, in which patients are not yet symptomatic but have positive serologic markers, as occurs in rheumatoid arthritis and systemic lupus erythematosus, said Dr. Paul Lochhead at Massachusetts General Hospital in Boston, and his associates. “To our knowledge, no previous study has examined prediagnostic inflammatory markers in relation to IBD risk,” the investigators added. “Characterizing preclinical inflammation in IBD could give insights into the natural history of [Crohn’s disease] and [ulcerative colitis], and might help identify potential windows for early therapeutic or preventive interventions in high-risk individuals.”
SOURCE: American Gastroenterological Society
The study included 83 patients with Crohn’s disease, 90 patients with ulcerative colitis, and 344 matched controls. Patients were from two national prospective cohort studies – the Nurses’ Health Study, which includes female nurses aged 35-55 years at enrollment, and the Nurses’ Health Study II, which includes female nurses aged 24-42 years at enrollment. Both studies are ongoing, with follow-up rates exceeding 90%. To assemble the cohort, the researchers extracted questionnaire data and then obtained medical records for blinded review. They confirmed diagnoses of Crohn’s disease and ulcerative colitis using standard case definitions, they said (Clin Gastroenterol Hepatol. 2016 Feb 13. doi: 10.1016/j.cgh.2016.01.016).
Participants testing in the highest quintiles for circulating hs-CRP and IL-6 were at greater risk of Crohn’s disease and ulcerative colitis than were those in the lowest quintiles, even after accounting for age, smoking status, body mass index, oral contraceptive use, and cumulative physical activity. For IL-6, odds ratios were 4.7 for Crohn’s disease (95% confidence interval; 1.9-11.5), and 3.4 for ulcerative colitis (95% CI; 1.4-8.2). For hs-CRP, odds ratios were 2.8 for Crohn’s disease (95% CI; 1.15-6.9) and 1.8 for ulcerative colitis (95% CI; 0.8-4.0). The longest interval between testing and diagnosis of IBD was 20 years, Crohn’s disease patients were diagnosed within 10 years, and patients testing in the upper quintile for the inflammatory markers were diagnosed an average of 10.6 years later, the researchers said.
Study participants tended to be in their early 50s when first tested, which exceeds the typical age of Crohn’s disease and ulcerative colitis onset and might limit the generalizability of the findings, the investigators said. They tried to eliminate confounding from undiagnosed baseline IBD by excluding participants diagnosed within 2 years of blood collection, they added. “The differences in overall median inflammatory marker levels between cases and control subjects in our study were small; however, differences of similar magnitude have been reported between groups with disparate outcomes in studies of cardiovascular disease,” they noted. “Moreover, when comparing extreme quintiles of median inflammatory marker levels, where risk of [Crohn’s disease] or [ulcerative colitis] was most evident, the differences were more substantial.”
The study was funded by the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases, Crohn’s and Colitis Foundation of America, and the American Gastroenterological Association. Dr. Lochhead had no disclosures. Two coinvestigators disclosed relationships with Exact Sciences, AbbVie, Cubist Pharmaceuticals, Bayer Healthcare, Pfizer, and Pozen.