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14. Infliximab for severe IV steroid-refractory ulcerative colitis: Can infliximab trough levels guide our management?

M. Ferrante1, V. Ballet1, V. Geskens2, S. Vermeire1, G. Van Assche1, A. Gils2, P. Rutgeerts1

1Department of Gastroenterology, University Hospital Gasthuisberg, Leuven, Belgium; 2Department of Pharmaceutical Biology, University Hospital Gasthuisberg, Leuven, Belgium

Aim: The optimal rescue therapy for severe IV steroid-refractory ulcerative colitis (UC) is still debated. Our aim was to evaluate the long-term outcome of maintenance therapy with infliximab (IFX) in patients with severe IV steroid-refractory UC and to define predictors of colectomy-free survival. In particular, we wanted to investigate if IFX trough levels (TL) could serve as a potential guidance for clinical practice.

Material and Methods: Thirty patients with severe IV steroid-refractory UC (10 female, median age at first IFX 39 years) received rescue therapy with IFX 5 mg/kg after a median of 8 days of IV steroids. At first IFX, median disease duration was 16 months, median CRP 35.7 mg/L, median hemoglobin 10.7 g/dL and median albumin 32.0 g/L. Furthermore, 90% had extensive colitis, 76% had a Mayo endoscopic subscore of 3 and 57% received azathioprine. Clinical response was judged by physician's assessment. Cumulative probabilities of colectomy-free survival were evaluated with Kaplan–Meier analysis. TL after IFX were analyzed using a in-house developed ELISA in 25 patients of whom serum was available.

Results: Twenty-three out of thirty patients (77%) achieved clinical response on the short-term, while 2 needed rescue therapy (1 new course of IV corticosteroids with azathioprine, 1 investigational drug) and 5 needed colectomy within 2 months. After a median follow-up of 35 months, 3 initial clinical responders were successfully bridged to azathioprine monotherapy, while 13 others maintained steroid-free clinical response under maintenance therapy with IFX. Three of these needed IFX dose escalation to maintain response. The remaining seven patients, initially achieving clinical response, needed rescue medical therapy later on (3 new course of corticosteroids, 4 adalimumab). Two of them underwent colectomy 11 and 13 months after first IFX, respectively. All patients treated had detectable TL at week 2. By using quartile analysis, we did not observe a significantly higher colectomy rate in patients with lower TL (Q1 33%, Q2 20%, Q3 0% and Q4 17% colectomy, p = 0.323). Similarly, TL at week 14 and 30 did not predict colectomy-free survival. Short-term clinical response (Breslow p < 0.001), short-term mucosal healing (p = 0.032) and normalization of CRP (p = 0.029) were predictors of colectomy-free survival. A baseline hemoglobin <12 g/dL and a Mayo endoscopic subscore of 3 showed a trend towards higher colectomy rates (p = 0.093 and 0.117). During follow-up, no mortality was observed. Three patients developed an acute infusion reaction, one a severe pneumonia.

Conclusion: During a median follow-up of 35 months, 23% of patients with IV-steroid refractory UC receiving rescue IFX needed colectomy, while 53% experienced sustained steroid-free clinical response. Short-term clinical response, mucosal healing and biological response were associated with colectomy-free survival. TL did not predict colectomy-free survival. These initial results suggest that measuring TL in this subgroup of severely ill patients is not useful for outcome prediction, although more data are needed.