Ustekinumab dose intensification after secondary loss of response in Crohn’s disease (RESCUE study)
Bossuyt P et al, Gastroenterology. 2026;171(1):99-109
In this randomized trial of Crohn’s patients with secondary loss of response to ustekinumab, dose intensification with a single i.v. administration followed by s.c. applications every 4 weeks was not more effective compared to a single i.v. administration followed by s.c. applications every 8 weeks.
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 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 < 250 μg/g and no steroids in the 90 days before week 48.
Results: Between March 2020 and October 2023, 108 patients were randomized. Steroid-free clinical remission at week 48 was reached in 15% vs. 19% of patients in the every 4 weeks vs. the every 8 weeks group (difference 4%; p = 0.5). Serious adverse events occurred in 17% vs. 13% of patients.
Conclusions: 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 1 intravenous administration followed by 8 weekly subcutaneous dosing of ustekinumab.