Background and 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 two 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 q8 weeks and experiencing a secondary loss of response (PRO-2: abdominal pain (AP) score >1 and liquid or very soft stool frequency (SF) >3 and an objective documentation of disease). Patients were randomized 1:1 to receiving a single intravenous re-induction with ustekinumab ≈ 6mg/kg followed by either subcutaneous ustekinumab 90 mg q4 weeks or q8 weeks till week 48. The primary endpoint was the proportion of patients with steroid-free clinical remission at week 48, defined as PRO-2 remission: (AP ≤ 1 AND SF ≤3) and fecal calprotectin <250μg/g and no steroids in the 90 days prior to week 48.
Results: Between March 2020 and October 2023, 108 patients were randomized. Steroid free clinical remission at week 48 was reached in 15% versus 19% of patients in the Q4W versus the Q8W group (difference 4%; p=0.5). Serious adverse events occurred in 17% vs 13% of patients.
Conclusion: In patients with CD and secondary loss of response to ustekinumab, dose-intensification with a single intravenous administration and followed by 4 weekly subcutaneous dosing of ustekinumab was not more effective than one intravenous administration followed by 8 weekly SC dosing of ustekinumab.
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