BACKGROUND: Advanced combination therapy with biologics and small molecules has seen more widespread implementation for inflammatory bowel disease (IBD). However, there is a paucity of data available to guide the successful de-escalation of combination therapy following the achievement of disease remission. Therefore, we pursued this retrospective study to evaluate our center's approach to de-escalation of these patients. METHODS: IBD patients undergoing de-escalation of combination biologic therapy from May 2017 to March 2023 with a follow-up visit were included. The need for re-escalation, steroid therapy, and hospitalization at follow-up was compared between the de-escalation method, adherence, patient demographics, disease characteristics, and measures of disease activity. RESULTS: Fifty IBD patients underwent de-escalation, with a median age of 35.7 years. All 50 patients had a follow-up visit within a median of 168 (111) days. Patients were divided into two groups with 12 (24%) patients requiring re-escalation of therapy and 38 (76%) able to maintain or further de-escalate. Of those that required re-escalation, 3 (25%) required the use of systemic steroids and none required hospitalization for IBD. Non-adherence to the de-escalation plan significantly correlated with the need for re-escalation (P < .001). CONCLUSIONS: Patient adherence and the number of prior failed biologic therapies were identified as potential risk factors for re-escalation. The type of agent being de-escalated (biologic or Janus kinase inhibitors [JAKi] did not correlate with the need for re-escalation).