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13. Infliximab, azathioprine, or infliximab + azathioprine for treatment of moderate to severe ulcerative colitis: The UC SUCCESS trial

R. Panaccione1, S. Ghosh1, S. Middleton2, J.R.M. Velazquez3, I. Khalif4, L. Flint5, H.J. van Hoogstraten5, H. Zheng5, S. Danese6, P. Rutgeerts7

1University of Calgary, Calgary, AB, Canada; 2Addenbrookes Hospital, University of Cambridge, Cambridge, United Kingdom; 3Clínica Las Américas, Medellín, Colombia; 4State Scientific Centre of Coloproctology, Moscow, Russian Federation; 5Merck Research Laboratories, Kenilworth, NJ, United States; 6Istituto Clinico Humanitas, Milan, Italy; 7University of Leuven, Leuven, Belgium

Aim: To assess the best treatment strategy in patients with moderate-severe ulcerative colitis (UC) who are failing corticosteroids.

Materials and Methods: We conducted a 16-week, randomized, double-blind, controlled trial in biologic-naïve patients with moderate-severe UC (Mayo score ≥6) who were failing corticosteroids and either naïve to AZA, or had stopped AZA ≥3 months before entry. Subjects were randomized to one of three treatment arms: AZA 2.5 mg/kg + placebo; IFX 5 mg/kg + placebo; IFX 5 mg/kg + AZA 2.5 mg/kg. At week 8, non-responders (Mayo score reduction <1 point) in the AZA arm were eligible for IFX 5 mg/kg at weeks 8, 10, and 14. The primary endpoint was steroid-free remission at week 16 (total Mayo score ≤2). Secondary endpoints included response (decrease in total Mayo score of ≥3 points and at least 30% lower than baseline Mayo score) and mucosal healing (Mayo endoscopy subscore of 0 or 1) at week 16.

Results: 231 of 239 randomized patients were included in the analyses. Baseline demographics and medications were similar in all groups. Median age was 37 years (range 18–69 years). Mean total Mayo scores at baseline (SE) were 8.50 (0.15), 8.08 (0.15), and 8.54 (0.15) for AZA, IFX, and IFX+AZA groups, respectively. The primary endpoint was achieved: a significantly greater proportion of patients achieved steroid-free remission at week 16 in the IFX+AZA arm compared to the AZA arm. Clinical response and mucosal healing was achieved by greater proportions of patients in both IFX arms compared to the AZA arm. Stepwise improvement in change from baseline in total Mayo score and most individual subscores was demonstrated in the IFX arms compared to the AZA arm.

Table 1. Results summary
OutcomesIFX+AZA (n = 78)IFX (n = 77)AZA (n = 76)
Clinical endpoints, week 16 (proportion of patients)
Mucosal healing63%#55%#37%
Mayo score, week 16 (change from baseline)
Stool frequency−1.54#−1.23−0.97
Rectal bleeding−1.25#-1.14#−0.77
Physician's global assessment−1.30*#−1.06#−0.59
*P < 0.05 compared to IFX; #P < 0.05 compared to AZA.

Through week 8, other than an increase in hepatobiliary events in the AZA arm (16.46% vs 3.85% and 6.25% in the IFX and IFX+AZA groups respectively), overall safety was generally similar across groups and consistent with the known safety profile of IFX.

Conclusions: IFX+AZA was superior to AZA and IFX monotherapy in inducing steroid-free remission in patients with moderate-severe UC. Patients treated with an IFX-based strategy are more likely to achieve response and mucosal healing than those treated with AZA monotherapy.