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P145. Is elevated CRP a predictor of efficacy in ulcerative colitis? Post-hoc analysis from a placebo-controlled study with interferon-β-1a

W. Reinisch1, P. Mannon2, P. Miner3, A. McAllister4, Y. Xi4, F. Cataldi4

1Vienna University, Vienna, Austria; 2UAB, Birmingham, AL, United States; 3OFDR, Oklahoma City, OK, United States; 4Biogen, Cambridge, MA, United States

Aim: In Crohn's disease (CD) there is emerging evidence on improved outcomes to biologics in patients with elevated CRP as objective marker of inflammation. This correlates to evidence in CD clinical trials of improved efficacy of active treatments over placebo (P). In Ulcerative Colitis (UC) CRP is considered a less reliable biomarker of inflammation and disease activity. However, elevated CRP levels have been associated with an increased risk of colorectal cancer and colectomy in UC. Therefore, in UC clinical trials, data analysis has been mostly focused on elevated CRP in relationship to colectomy rates and not to efficacy. In a placebo-controlled study of Interferon-β-1a (IFN) conducted in North America and East Europe we performed a post-hoc analysis of the effect of elevated CRP on efficacy for clinical response and mucosal healing (MH).

Methods: Adult patients with moderate to severe UC were randomized to receive IFN 30 μg IM or P twice a week, for 12 weeks. The primary endpoint was clinical response at Week 8, defined as a decrease from baseline in the total Mayo score of at least 3 points and at least 30%, accompanied by a decrease in the subscore for rectal bleeding of at least 1 point or absolute subscore of 0 or 1. MH was a secondary endpoint, defined as absolute Mayo subscore for endoscopy of 0 or 1. The endoscopy subscore was expanded to a 5-point scale to increase sensitivity, therefore, the total Mayo score ranged from 0 to 13 points.

Results: The ITT-intent-to-treat population included 123 patients, 61 in P and 62 in IFN. At week 8, 53% of patients on IFN vs. 44% on P were in clinical response (p = 0.35); 50% on IFN and 36% on P had MH (p = 0.12).

Figure: Clinical response at Week 8 by baseline CRP (mg/L).

At baseline, nearly 50% of the patients (n = 59) had elevated CRP above the upper limit of normal (ULN) of 2.87 mg/lL, (28 P, 31 IFN). 24 patients had CRP of 10 mg/l ULN, (9 P, 15 IFN). In this subgroup of elevated CRP, we observed an increased rate of clinical response with IFN and a lower placebo rate (Figure).

The rates of mucosal healing were lower in both groups but maintained similar difference between groups: CRP above 2.87, IFN 45% and P 29%; CRP above 10, IFN 47% and P 22%.

Conclusions: In this study, IFN showed an overall positive trend towards efficacy at week 8. Nevertheless, these data showed that enhanced clinical efficacy of IFN is seen in UC patients with elevated CRP. In addition, as described in reports of drug testing in CD, subsets of patients with elevated CRP are associated with lower placebo response rates. Elevated CRP value should be evaluated a priori in larger studies in UC to test this hypothesis.