Aspirin in the Aetiology of Crohn's Disease and Ulcerative Colitis

A European Prospective Cohort Study

S. S. M. Chan; R. Luben; M. M. Bergmann; H. Boeing; A. Olsen; A. Tjonneland; K. Overvad; R. Kaaks; H. Kennedy; K.-T. Khaw; E. Riboli; A. R. Hart

Disclosures

Aliment Pharmacol Ther. 2011;34(6):649-655. 

In This Article

Results

A total of 35 participants developed CD at a median age of 56.9 years (range 39.8–78.7 years) of which 71% were women. A further 84 participants were diagnosed with UC at a median age of 60.0 years (range 39.8–78.7 years) of which 57% were men. The median time at which CD was diagnosed after recruitment was 4.6 years (range 1.5–9.6 years) and for UC it was 3.8 years (range 1.7–9.4 years) (Table 2). The percentage of participants from each country of the total cases who developed IBD was as follows: UK – CD = 31% (11/35), UC = 32% (27/84), Germany – CD = 37% (13/35), UC = 20% (17/84) and Denmark – CD = 31% (11/35), UC = 48% (40/84). In those who developed CD, 55% had disease affecting the terminal ileum, whilst 58% had disease affecting the large bowel (the detailed clinical data were available for 89% of all CD cases). For patients with UC, 68% developed a left sided colitis i.e. inflammation distal to the splenic flexure with 79% of UC participants having had the extent of their disease assessed by colonoscopy or barium enema. The aspirin data were complete for 100% of cases and controls in the CD analysis, 95% complete for cases and controls in the UC analysis and 99% complete for smoking. Cigarette smoking when adjusted for aspirin use, was positively associated with Crohn's disease (OR = 2.45, 95% CI = 1.04–5.77), but not ulcerative colitis (OR = 1.12, 95% CI = 0.61–2.06).

In the analysis from all countries, regular aspirin use was positively associated with the risk of developing CD (OR = 6.14, 95% CI = 1.76–21.35, P < 0.01) after adjustment for smoking with most of the effect contributed by women who made up over two-thirds of CD cases (women – OR = 12.40, 95% CI = 2.16–71.18, P < 0.01; men – OR = 1.62, 95% CI = 0.16–16.34). The attributable fraction of regular aspirin use and CD was 19%. The effect of regular aspirin was strongly associated with both CD of the small bowel (i.e. terminal ileum disease) (OR = 9.85, 95% CI = 1.72–56.55, P < 0.01) and large bowel (OR = 7.49, 95% CI = 1.16–48.37). There was evidence of an interaction between aspirin and smoking, as in participants who both took aspirin and smoked the odds ratio decreased (OR = 0.30, 95% CI = 0.03–3.08). No association was found between regular aspirin use and the development of UC (OR = 1.29, 95% CI = 0.67–2.46) and there were no interactions (Table 3). The above odds ratios were applicable to those who developed IBD after at least 18 months of recruitment to help exclude reverse causality bias. This bias was further reduced by recalculating the ORs after excluding patients diagnosed with inflammatory bowel disease less than 36 months after recruitment, CD (OR = 5.54, 95% CI = 1.17–26.21, P < 0.03) and UC (OR = 0.96, 95% CI 0.45–2.04). In Denmark, the centre recording aspirin use over the largest time, there was a positive association between regular aspirin intake and CD (OR = 6.53, 95% CI = 1.44–29.62) and none for UC (OR = 1.35, 95% CI = 0.61–2.98, P < 0.46). Analysis of data from the remaining centres, excluding Denmark produced a statistically nonsignificant OR of 1.68, (95% CI = 0.17–16.45). Finally to further confirm the effect of aspirin, rather than a class effect of analgesics, we calculated the odds ratio of regular paracetamol use in the Danish cohort. This showed no positive associations with CD (OR = 0.63, 95% CI = 0.16–2.48) or UC (OR = 1.57, 95% CI = 0.77–3.19).

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