Long-term efficacy of therapeutic drug monitoring-guided optimization of ustekinumab maintenance therapy for Crohn's disease patients.

Long-term remission in Crohn's disease (CD) remains challenging. While ustekinumab effectively induces remission, strategies to enhance its maintenance efficacy are urgently needed. This study evaluated therapeutic drug monitoring (TDM)-guided ustekinumab optimization for sustained CD management. A retrospective observational study was conducted involving 158 patients [TDM: n = 87, age(16 39), male = 64; Non-TDM: n = 71, age(16-40), male = 57] with moderate-to-severe CD who achieved clinical remission following ustekinumab therapy, between October 2020 and November 2024, sourced from three inflammatory bowel disease centers. All patients received 8 weekly ustekinumab maintenance treatment with or without therapeutic drug monitoring (TDM)-guided optimization. The clinical outcomes and disease relapse were evaluated at year 1 and 2. The non-TDM group had a slightly higher endoscopic response and mucosal healing rate at baseline, there were no statistically significant differences between two cohorts at baseline with respect to demographic and clinical characteristics. In this multicenter retrospective study of 158 CD patients in clinical remission, TDM-guided dosing (n = 87) significantly improved 1 year (83.9% vs. 70.4%, p = 0.042) and 2 year remission rates (71.3% vs. 46.5%, p = 0.002) compared to standard therapy (n = 71). Subgroup analyses confirmed benefits in endoscopic responders and mucosal healing cohorts. TDM patients exhibited higher ustekinumab trough levels (3.00 vs. 1.46 μg/mL at year 1, p < 0.001) and lower relapse rates (p = 0.003). Neither the TDM nor the non-TDM cohorts reported any severe adversative events. TDM-guided optimization of ustekinumab maintenance treatment is an efficacious and safe strategy for CD patients with ustekinumab induced clinical remission.