The Effect of Dose Intensification After Secondary Loss of Response to Ustekinumab in Crohn’s Disease: Results of the REScUE Study

BACKGROUND & AIMS: Secondary loss of response to ustekinumab is observed in patients with Crohn's disease (CD). Multiple dose-intensification regimens have been proposed. We aimed to test prospectively 2 different dose-intensification regimens with ustekinumab in patients with CD experiencing secondary loss of response. METHODS: This was an investigator-initiated, multicenter, randomized, placebo-controlled trial conducted at 15 hospitals in Belgium. Eligible patients were adults with CD treated with ustekinumab on maintenance dosing of 90 mg subcutaneous every 8 weeks and experiencing a secondary loss of response (Patient-Reported Outcomes 2: abdominal pain score >1 and liquid or very soft stool frequency >3 and an objective documentation of disease). Patients were randomized 1:1 to receiving a single intravenous reinduction with ustekinumab ≈6 mg/kg followed by either subcutaneous ustekinumab 90 mg every 4 weeks or every 8 weeks until week 48. The primary endpoint was the proportion of patients with steroid-free clinical remission at week 48, defined as Patient-Reported Outcomes 2 remission: (abdominal pain ≤ 1 and stool frequency ≤3) and fecal calprotectin