Abstract Background Ustekinumab, a monoclonal antibody of interleukin-12 and interleukin-23, was approved for the treatment of moderate to severe Crohn’s disease (CD) in 2016. Ustekinumab is approved in CD for a weight-based IV induction dose followed by every 8 weeks of subcutaneous dosing. Response rates by 6 weeks range from 34% (anti-TNF failures) to 56% in bio-naïve patients. The remainder includes patients who partially-respond (PR) or do not respond (NR). Response by week 16 is 55% (anti-TNF failures) and 73% in bio-naïve patients suggestive of a ‘delayed response’ in some. Experience with anti-TNF drugs demonstrates that a subset of patients respond to dose escalation, which prompts the notion of a potential delayed response phenomenon with Ustekinumab. Aim Determine the efficacy of dose escalation from standard Q8 dosing to Q4 dosing of Ustekinumab in CD patients, who had PR or NR to standard Q8 dosing. Methods A Retrospective observation study of 143 adult patients with CD, on Ustekinumab standard Q8 dosing over a 2 year and 9-month period was conducted. Data was extracted pertaining to demographics, disease, and treatment-related variables (biomarkers, steroid use, interval surgery, ER visits). Patients were further subcategorized as responders, partial responders(PR), and non-responders(NR), based on changes in fecal calprotectin, albumin, CRP, and Physician Global Assessment Disease Severity (1=mild, 2=moderate, 3=severe). Q8 non-responders (NR) and partial responders (PR) were dose-escalated to Q4, and outcome variables were collected. Biomarkers, steroid utilization, interval surgery, and ER visits, and PGA were compared in Q8 partial responder(PR) and non-responders (NR) from the date of starting Ustekinmuab on Q8 dosing to the date of escalation to Q4 dosing, versus the date of escalation Q4 dosing to the end of patient follow up. Results 30% (n=8) of patients were Q8NR, and 70% (n=19) were Q8PR). In the PR group, biomarkers decreased by up to 21% when these patients were switched to Q4 dosing. 100% of patients saw clinical improvement or remained at mild disease on Q4 dosing. In the NR group, biomarkers decreased by up to 91%. 100% of patients saw clinical improvement or remained at mild disease while on Q4 dosing. In both groups, 50% of patients taking steroids on Q8 dosing were no longer taking steroids or were at a reduced dose at the end of Q4 dosing follow-up. 40% of patients on immunomodulators on Q8 dosing were no longer taking immunomodulators at the end of Q4 dosing follow-up. Conclusions