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DOP003 Proximal disease extension in patients with limited ulcerative colitis: a Danish population-based inception cohort

Burisch J.*1, Vind I.2, Prosberg M.2, Colombel J.-F.3, Ungaro R.3, Bendtsen F.2, Vester-Andersen M.2,4

1North Zealand University Hospital, Department of Gastroenterology, Frederikssund, Denmark 2Hvidvore University Hospital, Gastrounit, medical section, Hvidovre, Denmark 3Susan and Leonard Feinstein IBD Clinical Center Icahn School of Medicine at Mount Sinai, Departments of Medicine and Pediatrics, New York, United States 4Zealand University Hospital, Department of Medical Gastroenterology, Køge, Denmark

Background

Disease extent classified in ulcerative colitis (UC) as E1 (proctitis), E2 (left-sided) or E3 (extensive) is one of the major factors determining disease prognosis over the long-term. UC is a progressive and dynamic disease. We investigated the risk of UC extension and subsequent risk of surgery in a Danish population-based cohort from the biological era.

Methods

All incident patients diagnosed with UC in a well-defined Copenhagen area 1.1.2003–31.12.2004 were followed prospectively until 31.12.2011. Disease extension was defined in patients with limited UC at diagnosis (E1 or E2) as a progression from the initial extent defined by endoscopy or surgery. The risk of colectomy was assessed in all incident patients. Associations between progression or colectomy and multiple covariates (age, gender, initial disease extent, type of medical treatment, diagnostic delay and smoking status) were analysed by Cox regression analyses using the proportional hazard assumption.

Results

Among a total of 300 incident UC patients 220 (73%) had E1 or E2 at diagnosis. Extent at diagnosis and during follow-up is shown in Table 1. During the follow-up period, 50 (23%) patients with E1/E2 progressed to E3, and 22 (10%) patients with E1 progressed to E2. Disease extent at diagnosis was the sole significant predictor of extension to E3 with a higher risk in E2 than in E1 patients (HR =2.2 CI95%: 1.2–4.2). No significant predictors were found for extension from E1 to E2.

During follow-up, a total of 34 (11%) patients had a colectomy. Of patients with E1/E2 as initial extent a total of 18 (8%) patients had a colectomy. Analyses of risk factors associated with colectomy are shown in Table 2. Progression from E1/E2 to E3, female gender and past history of smoking were significant risk factors for colectomy.

Table 1. Disease extent in UC at diagnosis and follow-up

At diagnosisAt follow-upTotal (diagnosis)
E1E2E3
E158 (26%)22 (10%)13 (6%)93 (42%)
E290 (41%)37 (17%)127 (58%)
Total (follow-up)58 (26%)112 (51%)50 (23%)220 (100%)

Table 2. Risk factors associated with colectomy in ulcerative colitis patients

Hazard ratio (95% CI)
Ex-smoker at diagnosis3.54 (1.26–9.94)
Younger age at diagnosis0.98 (0.95–1.02)
Gender (female vs male)2.86 (1.04–7.85)
Any increase in extension6.69 (0.39–113.92)
Extension from E1/ E2 to E39.80 (1.16–82.84)
Diagnostic delay <6 months2.65 (0.92–7.58)
Disease extent at diagnosis (E2 vs E1)0.72 (0.26–1.96)

Conclusion

After seven years follow-up, one out of three patients with limited UC experienced disease extension. Only extent at diagnosis was a clinical predictor for disease extension. The risk of colectomy was increased in ex-smokers, and patients who progressed to extensive colitis. This highlights the need of preventing progression in patients with limited UC as well as to identify new histological or molecular markers that enable physicians to identify patients at risk for disease progression.