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* = Presenting author

OP030 Factors associated with the first trough level of infliximab at week 2 that predicts short- and long-term outcomes in ulcerative colitis

T. Kobayashi*1, Y. Suzuki2, S. Motoya3, F. Hirai4, H. Ogata5, H. Ito6, N. Sato7, K. Ozaki7, M. Watanabe8, T. Hibi1

1Kitasato University Kitasato Institute Hospital, Centre for Advanced IBD Research and Treatment, Tokyo, Japan, 2Toho University Sakura Medical Centre, Department of Internal Medicine, Sakura, Japan, 3Sapporo-kosei General Hospital, Inflammatory Bowel Diseases Centre, Sapporo, Japan, 4Fukuoka University Chikushi Hospital, Department of Gastroenterology, Chikushino, Japan, 5Keio University School of Medicine, Centre for Diagnostic and Therapeutic Endoscopy, Tokyo, Japan, 6Kitano Hospital The Tazuke Kofukai Medical Research Institute, Digestive Disease Centre, Osaka, Japan, 7Mitsubishi Tanabe Pharma Corporation, Osaka, Japan, 8Tokyo Medical and Dental University, Department of Gastroenterology and Hepatology, Tokyo, Japan

Background

Infliximab (IFX), anti-tumour necrosis factor-alpha (TNF-α) antibody, is one of the treatment options for refractory ulcerative colitis (UC). Early decision making between continuing IFX and switching to other options is critical in treating acute flares of UC. We demonstrated that the higher first trough level (TL) of IFX at week 2 predicts the better future outcomes with a cut-off of 21.3 μg/mL (J Gastroenterol 2015), suggesting the usefulness of the first TL for early decision making and the benefit of dose intensification in patients with low TL. We further conducted a post-hoc analysis of the phase 3 trial to investigate factors associated with the first TL to understand the pharmacokinetics of IFX and to identify the patients who require dose optimisation.

Methods

In this phase 3 trial for UC, patients received intravenous IFX 5 mg/kg or placebo at weeks 0, 2, and 6. Patients showed their response by week 8 and continued IFX at weeks 14 and 22. TL was measured by enzyme-linked immunosorbent assay. Eighty-two patients who received the initial 3 infusions of IFX and evaluated until week 14 were included in this post-hoc analysis. Associations between baseline factors and the first TL were examined.

Results

The first TL ≥ 21.3 μg/mL (p = 0.038) and baseline CRP (p = 0.027) were selected as predictors of 14 week clinical remission by logistic model. Further, patients with the first TL ≥ 21.3 μg/mL were significantly more likely to achieve clinical remission than patients with the first TL < 21.3 μg/mL were, especially amongst those who had elevated CRP (> 0.5 mg/dL) (77% vs 26%, p = 0.005). Correlation analysis indicated that weight (r = 0.254), Mayo endoscopic sub score (r = -0.251), C-reactive protein (r = -0.324), albumin (r = 0.410), haemoglobin (r = 0.365), and plasma interleukin-6 (r = -0.347) were significantly associated with the first TL. A general linear model showed that the first TL was correlated with CRP (p = 0.035), albumin (p = 0.042), and haemoglobin (p = 0.015).

Conclusion

The first TL had more effect on the primary response in patients with elevated CRP. CRP, albumin, and haemoglobin were correlated with the first TL at week 2, suggesting that these factors may identify the patients who require treatment modification to obtain the sufficient first TL. In contrast, patients who did not achieve clinical remission despite the sufficient first TL might have TNF-unrelated inflammation, which would not respond to IFX regardless of the TL.