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* = Presenting author

P607 Histologic activity after acute treatment with multimatrix mesalazine for ulcerative colitis may predict long-term remission status

G. D'Haens*1, G. De Hertogh2, J.R. Turner3, H. Wan4, B. Adeyi4, D.T. Rubin5

1Academic Medical Centre, Department of Gastroenterology and Hepatology, Amsterdam, Netherlands, 2University Hospitals Leuven, Department of Pathology, Leuven, Belgium, 3The University of Chicago Medicine, Department of Pathology, Chicago, IL, United States, 4Shire, Biostatistics, Wayne, PA, United States, 5The University of Chicago Medicine, Inflammatory Bowel Disease Center, Chicago, IL, United States

Background

For patients with active mild-to-moderate ulcerative colitis (UC), mesalazine (5-aminosalicylic acid) is recommended first-line treatment. While endoscopic assessments are commonly used to assess treatment efficacy in UC, relatively few studies have examined histology scores over the course of treatment. Results of a post hoc analysis are presented, examining the relationship between remission status and histology scores in patients with UC during acute and maintenance treatment with multimatrix mesalazine.

Methods

In this open-label, multicenter, prospective phase 4 study (ClinicalTrials.gov ID: NCT01124149), adult patients with active mild-to-moderate UC were administered multimatrix mesalazine 4.8 g/d once-daily (QD) for 8 weeks (acute phase); those in complete or partial remission following acute treatment were eligible for 12 months of maintenance treatment with multimatrix mesalazine 2.4 g/d QD. Complete or partial remission was defined using a modified UC-Disease Activity Index that evaluated symptom, endoscopy, and Physician's Global Assessment scores. At Baseline (Week 0) and endpoints for the acute (Week 8/Month 0) and maintenance (Month 12) phases, 2 or 4 biopsies were taken (when endoscopy was performed) and evaluated by 2 blinded pathologists. Histology scores were based on a modified Geboes grading scale (range 0-6) for assessment of inflammation. Inter-rater reliability of matched sample pairs was examined using Cohen's kappa with Fleiss-Cohen weights. Remission status (complete, partial, or none) at Month 12 was stratified by maximum histology score (cutoff score at 3.1) at Month 0.

Results

Measurement of inter-rater reliability between histology readers produced a Cohen's weighted kappa coefficient of 0.60 (moderate strength of agreement; 95% confidence interval, 0.33-0.87). A higher proportion of patients with low (<3.1) versus high (≥3.1) maximum histology scores at Month 0 were in complete remission at Month 12 (41.3% vs 27.4%). Also, fewer patients with low versus high histology scores at Month 0 were not in remission at Month 12 (8.1% vs 14.4%).

Conclusion

A low degree of inflammation (maximum histology score <3.1) prior to maintenance treatment with multimatrix mesalazine was associated with a higher likelihood of complete remission after 12 months of maintenance therapy. These findings suggest that histology may be considered as a viable UC treatment endpoint.