Not Yet RecruitingPhase 3

Ustekinumab and Upadacitinib for Induction and Maintenance Therapy in Patients With Refractory Crohn's Disease: A Multicenter, Randomized, Parallel-Controlled Study

454 participantsStarted 2025-09-10

Plain-language summary

Crohn's disease is a chronic inflammatory bowel disorder characterized primarily by abdominal pain and diarrhea \[1,2\]. Conventional treatments include corticosteroids and immunosuppressants (such as azathioprine, mercaptopurine, and methotrexate) \[2,3\]. The introduction of anti-tumor necrosis factor-α (TNF-α) inhibitors, such as infliximab and adalimumab, has significantly improved outcomes for patients with Crohn's disease, reducing complications and hospitalization rates \[4\]. However, both infliximab and adalimumab may lead to primary or secondary failure due to various reasons, including immunogenicity \[5\]. Novel biologics and small molecule drugs, such as ustekinumab and upadacitinib, offer new hope for the treatment of refractory Crohn's disease patients. Ustekinumab is a monoclonal antibody targeting the p40 subunit of human interleukin (IL)-12/23. In the UNITI-2 study, the clinical remission rate at week 8 was 40% in the ustekinumab group, significantly higher than the 20% observed in the placebo group \[6\]. In the STARDUST study, the clinical remission rate at week 16 reached 68% in biologic-naïve patients and remained as high as 65% even in patients who had failed prior biologic therapy \[7\]. Upadacitinib is an orally administered JAK1 inhibitor that has now been approved for Crohn's disease in our region. In the recent U-EXCEED study, which enrolled refractory Crohn's disease patients who had failed at least one prior biologic therapy, the clinical remission rate at week 12 was 38.9%, significantly higher than that of the placebo group \[8\]. However, there is a lack of active head-to-head studies comparing the efficacy and safety of these two novel agents. Our objective is to evaluate the efficacy and safety of ustekinumab and upadacitinib in the treatment of refractory Crohn's disease, thereby providing a theoretical basis for clinicians and patients in making informed therapeutic decisions.

Who can participate

Age range18 Years

SexALL

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Inclusion criteria

✓. No history of latent or active TB prior to screening, except for the following:
✓. No signs or symptoms suggestive of active TB based on medical history and/or physical examination;
✓. No known recent close contact with an active TB patient, or if such contact has occurred, the subject should be referred to a TB specialist for additional evaluation and, if necessary, receive appropriate treatment for latent TB before or concurrently with the first dose of the study drug;
✓. Within 2 months prior to the first dose of the study drug:
✓. Within 3 months prior to the first dose of the study drug, a chest imaging examination performed by a qualified radiologist shows no evidence of current active TB or old inactive TB;

Exclusion criteria

✕. Any other experimental drug for Crohn's disease, unless at least 3 months or 5 half-lives have passed since the last dose;
✕. Intravenous corticosteroid therapy within 3 weeks prior to baseline;
✕. Immunosuppressants such as azathioprine, 6-mercaptopurine, methotrexate, etc., within 4 weeks prior to baseline;

What they're measuring

clinical remission rate

Timeframe: 16th week

Trial details

NCT IDNCT07149467

SponsorSixth Affiliated Hospital, Sun Yat-sen University

Sponsor typeOTHER

Study typeINTERVENTIONAL

Primary completion2026-12-31

Contact for this trial

Xiang Peng Xiang Peng, Dr

+86 18302076916 pengxiang5@mail.sysu.edu.cn

View on ClinicalTrials.gov More Crohn's Disease Aggravated trials