Prospective Evaluation of Ustekinumab Dose Intensification in Inflammatory Bowel Diseases.

BACKGROUNDS AND AIMS: Ustekinumab is an effective therapy for moderate-to-severe inflammatory bowel diseases (IBD), including Crohn's disease (CD) and ulcerative colitis (UC). However, secondary loss of response to standard every-8-week maintenance dosing is common. Prospective data supporting dose intensification are limited. To prospectively evaluate the effectiveness and safety of ustekinumab dose intensification to every 4 weeks (q4w) or every 6 weeks (q6w) in patients with IBD experiencing secondary loss of response. METHODS: We conducted a prospective cohort study of adults with CD or UC undergoing empiric ustekinumab dose intensification to q4w or q6w. Clinical disease activity was assessed using the Harvey-Bradshaw Index for CD and the Simple Clinical Colitis Activity Index for UC at baseline and following intensified maintenance dosing. The primary outcome was steroid-free clinical remission after the third intensified dose. Secondary outcomes included clinical response, biochemical response using fecal calprotectin, changes in serum ustekinumab concentrations, and adverse events. RESULTS: Nineteen patients (12 CD, 7 UC) were enrolled. After the third intensified dose, steroid-free clinical remission was achieved in 75.0% of CD and 71.4% of UC patients, while over 80% of patients achieved clinical response. Outcomes were similar between q4w and q6w regimens. Serum ustekinumab concentrations increased significantly following dose intensification, whereas biochemical response rates were modest. No new safety signals were observed, and no patients discontinued therapy due to adverse events. CONCLUSION: Ustekinumab dose intensification to q4w or q6w was safe and associated with improved clinical outcomes in this prospective IBD cohort.