Transmural Healing is Associated With Higher Biological Drug Concentrations than Mucosal Healing in Crohn Disease

BACKGROUND: Transmural healing (TH) is becoming a new and powerful therapeutic goal of Crohn disease (CD). However, the association between TH and serum trough levels of adalimumab/ustekinumab is unclear. The authors aimed to investigate this association and compare the difference in drug concentration between TH and mucosal healing (MH). METHODS: In this multicenter retrospective study, 302 consecutive patients during adalimumab/ustekinumab maintenance therapy were included. TH was defined as endoscopic MH in combination with ultrasonographic healing. Receiver operating characteristic curve and logistic regression were used in the association analysis. RESULTS: Forty-eight patients (15.9%) achieved TH and 104 patients (34.4%) achieved only MH. Patients achieving TH had significantly higher median drug concentrations than those achieving only MH [adalimumab: 15.0 (interquartile range, 10.5-20.0) versus 9.9 (interquartile range, 7.2-15.7) mcg/mL, P = 0.02; ustekinumab: 6.2 (interquartile range, 3.1-9.1) versus 3.7 (interquartile range, 1.6-6.0) mcg/mL, P = 0.01]. When drug concentrations were stratified by quartiles or octiles, the rate of TH was lower than that of MH in each concentration interval. Receiver operating characteristic analysis showed that the optimal cutoff concentration for TH was higher than that for MH (adalimumab: 10.3 vs 6.4 mcg/mL; ustekinumab: 5.4 vs 3.3 mcg/mL). High biological drug concentration was also an independent factor associated with TH (odds ratios, 9.90; P < 0.01). CONCLUSIONS: TH is associated with higher biological drug concentrations than MH in CD. Clinical trials are needed to further investigate whether dose escalation in patients with MH is helpful to achieve TH and evaluate the cost-effectiveness of this treat-to-TH strategy.