P382 Serum Ustekinumab Concentrations are Associated with Improved Outcomes with the Magnetic Resonance Index of Activity for Crohn's Disease

Chen, K.(1,2)*;Chen, J.(3);Smith, E.(1,2);Mathani, P.(1,2);Longman, R.(1,2);Lukin, D.(1,2);Scherl, E.(1,2);Battat, R.(1,2);

(1)Weill Cornell Medicine, Division of Gastroenterology- Department of Medicine, New York, United States;(2)Weill Cornell Medicine, Jill Roberts Center for Inflammatory Bowel Disease, New York, United States;(3)Weill Cornell Medicine, Department of Radiology, New York, United States;

Background

Controversy exists for ustekinumab concentrations needed in Crohn’s disease (CD). No data exist comparing ustekinumab concentrations and validated radiologic outcomes.  We characterized these relationships and clarified concentrations needed.

Methods

CD patients on maintenance (> 16 weeks) ustekinumab with both ustekinumab concentrations and simplified magnetic resonance index of activity (sMaRIA) scoring were included. Ustekinumab concentrations were compared between those with and without (1) radiologic remission (sMaRIA < 2), (2) severe radiologic inflammation (sMaRIA < 3) and (3) fecal calprotectin (FCP) biomarker remission (FCP < 50μg/g). Area under the receiver-operating characteristic (AUROC) curve determined optimal ustekinumab concentrations. Outcomes were compared between patients above and below identified ustekinumab thresholds.

Results

Thirty-eight paired ustekinumab concentrations and magnetic resonance enterography imaging results were included. Ustekinumab concentrations were higher with radiologic remission (11.4μg/mL vs. 6.4μg/mL, P=.005) and had good diagnostic accuracy for radiologic remission (AUROC 0.76, 95% CI 0.60 – 0.91) and for absence of severe inflammation (AUROC 0.71, 95% CI 0.55 – 0.88, optimal concentration 8.4μg/mL). With ustekinumab ≥8.4μg/mL, higher proportions had radiologic remission (63.2% vs. 21.1%, P=.01) and absence of severe inflammation (78.9% vs. 36.8%, P=.01) compared to patients with lower concentrations. Ustekinumab concentrations had good diagnostic accuracy (AUROC 0.73, 95% CI 0.52 – 0.94) for FCP biomarker remission (optimal concentration: 6.1μg/mL). Patients with ustekinumab concentrations ≥6.1μg/mL had higher proportions with biomarker remission (72.2% vs. 12.5% P<.01) compared to those with lower concentrations.

Conclusion

Ustekinumab concentrations are associated with radiologic and biomarker outcomes in CD. These data validate the need for higher ustekinumab concentrations.