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P596 Trough concentration of ustekinumab was a useful biomarker for the prediction of treatment-effects in patients with Crohn’s Diseases.

Kato, S.(1);Yamaga, N.(1);Ishibashi, A.(1);Kani, K.(1);Yakabi, K.(1);Nagoshi, S.(1);

(1)Saitama Medical Centre- Saitama Medical University, Department of Gastroenterology and Hepatology, Kawagoe City- Saitama, Japan

Background

Ustekinumab, anti-IL12/23 antibody have contributed to the good prognosis in patients with Crohn’s disease (CD). However, good biomarkers for the prediction of treatment- effects of ustekinumab (UST) are not clear. We elucidated whether trough concentration of UST could predict the clinical remission and seronegative inflammation in CD patients in clinical practice.

Methods

This was a single-centre prospective observational study approved by the institutional review board of our hospital. Forty CD patients treated by administration of intravenous UST 6 mg/kg and subcutaneous UST 90mg every 8 weeks were enrolled in this study. CDAI, serum CRP and plasma UST trough concentration were evaluated at every visit. All data were examined in total patients, patients with UST induction at remission state after pretreatment (Induction at remission group) and patients with UST induction at active state after pretreatment (Induction at non-remission group). Endpoints were time course changes of clinical remission rate, CDAI, CRP and UST trough concentration until week 40.

Results

In total, 40 participants were included in the final analysis. The mean age and disease duration of the participants were 41.3 and 11.7 years. Of the participants, 65% (26/40) were male, 25% (10/40) used thiopurine, and 30% (12/40) used steroids. TNF-failure of the patients were 65.0% (26/40). Remission rate of total patients significantly increased at week 8 (30, 60, 68, 78, 78, and 73% at every 8 weeks from baseline). Both CDAI and CRP significantly decreased from baseline at week 8. Remission rate of Induction at remission group (n=12) did not significantly decrease from baseline (100, 92, 92, 92, 92, and 83% at every 8 weeks from baseline). Remission rate of Induction at non-remission group (n=28) significantly increased until week 24 from baseline (0, 46, 57, 71, 71, and 68% at every 8 weeks from baseline). Trough concentrations of total patients at week 8, 16, 24 were 3.54, 1.57 and 1.43 μg/mL, respectively. Trough at each week was not significantly different between Induction at remission and at non-remission groups. Immunomodulator use did not affect trough concentration. Cut-off values of prediction for remission at week 8, 16, and 24 were 2.80, 1.28* and 1.12* μg/mL, respectively. Cut-off values of prediction for normal CRP at week 8, 16, and 24 were 3.27, 1.24* and 1.24* mg/mL, respectively (*: Each factor significantly could be detected).

Conclusion

UST trough concentration at subcutaneous injection could predict clinical remission and normal CRP. Pretreatment did not affect UST trough concentration.

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