S729 Serum Ustekinumab Concentrations Are Associated With Improved Outcomes With the Magnetic Resonance Index of Activity for Crohn's Disease

Abstract

Introduction: 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 < 50 μg/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 MRE were included. Ustekinumab concentrations were higher with radiologic remission (11.4 μg/mL vs. 6.4 μg/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 8.4 μg/mL). With ustekinumab ≥ 8.4 μg/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: 6.1 μg/mL). Patients with ustekinumab concentrations ≥ 6.1 μg/mL had higher proportions with biomarker remission (72.2% vs. 12.5% P < .01) compared to those with lower concentrations. (Figure) Conclusion: Ustekinumab concentrations are associated with radiologic and biomarker outcomes in CD. These data validate the need for higher ustekinumab concentrations.Figure 1.: (A) Receiver-operating characteristic curve analysis for sMaRIA score of < 2, absence of any inflammation, based on ustekinumab trough concentrations. The optimal concentration is 8.4 μg/mL as indicated by the best receiver-operating characteristic curve (area under curve, 0.76; sensitivity, 75%; specificity 68%). (B) Receiver-operating characteristic curve analysis for sMaRIA score of < 3, absence of severe inflammation, based on ustekinumab concentrations. The optimal serum concentration is 8.4 μg/mL as indicated by the best receiver-operating characteristic curve (area under curve, 0.71).