Background and Aim <p>Ustekinumab (UST) Clinical Decision Support Tool (UST–CDST) was introduced to predict clinical remission at 16&#xa0;weeks in patients with active CD who were treated with UST enrolled in the UNITI trial. Controversy still remained regarding the effectiveness of UST with concomitant immunomodulator and the criteria for patients who could benefit from concomitant therapy. The aim of the study was to evaluate the effect of UST with concomitant immunomodulator on relapses in patients with CD and the feasibility of UST–CDST as a patient selection tool for concomitant immunomodulator.</p> Methods <p>Between January 2021 and July 2023, patients with moderate-to-severe CD refractory to conventional therapies and treated with UST were enrolled at four tertiary hospitals. Patients who achieved a clinical response after UST induction were included. Clinical relapse (CR) was defined as admission, steroid, surgery, or biologics changes. Kaplan–Meier analysis was performed to evaluate the efficacy of UST with immunomodulator and to investigate the screening ability of UST–CDST for concomitant immunomodulator selection.</p> Results <p>Among 53 patients, cumulative relapse rate differed significantly between those receiving concomitant immunomodulator and those treated with UST alone (<i>p</i> = 0.024). Patients classified as low-to-intermediate-probability responders by UST–CDST who received combination therapy demonstrated a significantly higher relapse-free survival rate (<i>p</i> = 0.046). However, this trend was not observed in high-probability responders (<i>p</i> = 0.439).</p> Conclusion <p>In this study, the concomitant use of an immunomodulator with UST was associated with a reduced risk of CR. This effect was particularly evident in the low-to-intermediate-probability responder group. The UST–CDST might serve as a useful tool for guiding decisions regarding the use of concomitant immunomodulator in clinical practice.</p>