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P471 Infliximab trough levels are lower in patients with acute severe, compared to moderate-severe ulcerative colitis patients

B. Ungar*1, Y. Mazor2, H. Yanai3, Y. Ron3, A. Waizbard3, M. Yavzori1, E. Fudim1, O. Picard1, R. Loebstein4, U. Kopylov1, I. Dotan3, Y. Chowers2, R. Eliakim1, S. Ben-Horin1

1Sheba Medical Center & Sackler School of Medicine, Gastroenterology, Tel Hashomer, Israel, 2Rambam Health Care Campus & Bruce Rappaport School of Medicine, Technion Institute of Technology, Department of Gastroenterology, Haifa, Israel, 3Tel Aviv Sourasky Medical Center, affiliated to the Sackler Faculty of Medicine, Tel Aviv University, IBD Center, Department of Gastroenterology and Liver Diseases, Tel Aviv, Israel, 4Sheba Medical Center & Sackler School of Medicine, Institute of Clinical Pharmacology, Tel Hashomer, Israel

Background

Infliximab is effective as salvage therapy for patients with steroid refractory acute severe ulcerative colitis (ASUC). Moderately-severe colitis (MSUC) is defined as an ulcerative colitis exacerbation which requires infliximab therapy, although not severe enough to require hospitalization. Data comparing infliximab trough levels (TL) in patients with ASUC versus MSUC are scarce. Our aim was to examine whether infliximab drug and anti-infliximab antibodies (ATI) TL during induction differ between patients with ASUC and MSUC.

Methods

Infliximab and ATI TL 14 days after the first 5mg/kg infusion were compared in hospitalized ASUC and MSUC patients. Response status and immunomodulator use were matched. Continuous and categorical variables were analyzed using the Mann-Whitney U-test and Fisher's exact test, respectively.

Results

Fourteen patients with intravenous steroid refractory ASUC treated with infliximab 5mg/kg "salvage" therapy were compared to 14 matched MSUC controls. Mean infliximab TL at day 14 were significantly lower in patients with ASUC compared to MSUC (8 ± 5.5 versus 18.5 ± 11.4 mcg/ml, p=0.015). ATI formation rate (50%vs.21%, p=0.24) did not differ between the groups, although there was a trend for higher ATI levels (4.7 ± 5 vs. 2.6 ± 4.7 mcg/mleq, p=0.13) among the ASUC patients. Four patients (2 ASUC and 2 MSUC) were primary non-responders to infliximab. However, infliximab level at day 14 did not differ between responders and non responders (14.2 ± 10.6 vs. 7.3 ± 6.9 mcg/ml respectively, p=0.2).

Conclusion

Lower infliximab TL in patients with ASUC compared to MSUC may possibly be due to a higher inflammatory burden and/or increased drug clearance, perhaps via fecal loss of infliximab. Controlled trials are required in order to determine whether an a-priori intensified infliximab induction therapy would result in higher drug levels and thus an improved outcome in ASUC patients.