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

Conditions

• Crohn's Disease Aggravated
• Crohn's Disease in Remission

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Ustekinumab (approximately 6 mg/kg) — DRUG
  At Week 0: ≤55 kg: 260 mg administered by intravenous (IV) infusion. \>55 kg and ≤85 kg: 390 mg administered by intravenous (IV) infusion. \>85 kg: 520 mg administered by intravenous (IV) infusion. From Week 8 onward (i.e., at Week 8 and then every 8 weeks up to Week 52 or the end of the follow-up period): 90 mg administered by subcutaneous (SC) injection.
• Upadacitinib — DRUG
  From Week 0 to Week 12: 45 mg once daily, administered orally. From Week 13 through Week 52 or the end of the follow-up period: 30 mg once daily, administered orally.

Study Details

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.

Key Dates

Start date

Sep 10, 2025

Status verified

Aug 2025

Primary completion

Dec 31, 2026

Completion

Dec 31, 2027

Study Design

Enrollment

454 participants (estimated)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: Ustekinumab Group
  At Week 0: ≤55 kg: 260 mg administered by intravenous (IV) infusion. \>55 kg and ≤85 kg: 390 mg administered by intravenous (IV) infusion. \>85 kg: 520 mg administered by intravenous (IV) infusion. From Week 8 onward (i.e., at Week 8 and then every 8 weeks up to Week 52 or the end of the follow-up period): 90 mg administered by subcutaneous (SC) injection.
• Active Comparator: Upadacitinib Group
  From Week 0 to Week 12: 45 mg once daily, administered orally. From Week 13 through Week 52 or the end of the follow-up period: 30 mg once daily, administered orally.

Primary Outcome Measure

clinical remission rate [ Time Frame: 16th week ]

Central Contacts

• Xiang Peng Xiang Peng, Dr
  +86 18302076916
  [email protected]