Comparative Effectiveness of Upadacitinib vs Corticosteroids as First-Line Therapy for Acute Severe Ulcerative Colitis（UPFRONT）

Comparative Effectiveness of Upadacitinib vs Corticosteroids as First-Line Therapy for Acute Severe Ulcerative Colitis: Multicenter, Open-label, Non-inferiority, Randomized Controlled Study

The goal of this clinical trial is to learn comparative effectiveness and safety of Upadacitinib vs Corticosteroids as First-Line Therapy for Acute Severe Ulcerative Colitis. The main questions it aims to answer are:

1. Whether upadacitinib can effectively induce remission in acute severe ulcerative colitis with an efficacy non-inferior to that of corticosteroids.
2. What adverse reactions may occur with upadacitinib in the treatment of acute severe ulcerative colitis?

Researchers will compare upadacitinib with corticosteroids to evaluate the efficacy of upadacitinib in the treatment of acute severe ulcerative colitis.Participants will:

1. Upadacitinib group: Upadacitinib extended-release tablets 45 mg once daily for 8 weeks, then adjusted to 30 mg once daily.
2. Corticosteroid group: Methylprednisolone for injection 60 mg/day. If clinical response is achieved, switch to oral prednisone acetate tablets after 5 days (calculated at 0.75 mg/kg/day), followed by a weekly prednisone taper of 5 mg. When the dose is reduced to 20 mg, taper by 2.5 mg weekly until discontinued, with mesalazine 4 g/day as maintenance therapy.
3. Take drug Upadacitinib or Corticosteroid every day for 3 months
4. Visit the clinic once every 2 weeks for checkups and tests
5. Record the patient's bowel movements and the presence of symptoms such as abdominal pain, while performing colonoscopy, ultrasound examination, and blood tests at the specified time points.

Study Overview

• Status: Recruiting
• Conditions: Acute Severe Ulcerative Colitis
• Intervention / Treatment: Drug: Upadacitinib; Drug: Corticosteroid

• Study Type: Interventional
• Enrollment (Estimated): 46
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Yongquan Shi; Phone Number: +8602984771535; Email: von15991351319@163.com

Study Locations

• China
  • Shaanxi
    • Ankang, Shaanxi, China, 710005
      • Recruiting
      • Ankang Central Hospital
      • Contact: PengFei Yin, Ph. D; Phone Number: 86-0915-3214355; Email: 943030513@qq.com
    • Hanzhong, Shaanxi, China, 710005
      • Recruiting
      • 3201 Hospital
      • Contact: Kun Liu, Dr; Phone Number: 86-0916-2383201; Email: lk00086@sina.com
    • Xi'an, Shaanxi, China, 710005
      • Recruiting
      • Xijing Hospital
      • Contact: Yongquan Shi, Ph. D; Phone Number: 86-029-84771535; Email: shiyquan@fmmu.edu.cn
    • Xianyang, Shaanxi, China, 710005
      • Recruiting
      • Shaanxi Provincial Nuclear Industry 215 Hospital
      • Contact: Lei Lei, Dr; Phone Number: 86-029-32088156; Email: jiaozexuandll@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients diagnosed with ASUC
• Aged 18 years or older.
• No gender restriction.

Exclusion Criteria:

• Presence of contraindications, allergy, or intolerance to upadacitinib or glucocorticoids.
• Patients requiring immediate colectomy; diagnosis of Crohn's disease; confirmed intestinal infection; hemodynamic instability; clinically significant cytomegalovirus infection; current malignancy.
• Presence of severe underlying systemic diseases involving the heart, lungs, liver, kidneys, hematologic system, or other organ systems.
• Pregnant or breastfeeding women.
• Unwilling to participate in the clinical study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Upadacitinib group; Upadacitinib extended-release tablets 45 mg once daily for 8 weeks, then adjusted to 30 mg once daily.	Drug: Upadacitinib; Safety and efficacy of the drug
Active Comparator: Corticosteroid group; Methylprednisolone for injection 60 mg/day. If clinical response is achieved, switch to oral prednisone acetate tablets after 5 days (calculated at 0.75 mg/kg/day), followed by a weekly prednisone taper of 5 mg. When the dose is reduced to 20 mg, taper by 2.5 mg weekly until discontinued, with mesalazine 4 g/day as maintenance therapy.	Drug: Corticosteroid; Safety and efficacy of the drug

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Outcome Measure	clinical response by day 7 (defined as a reduction in Lichtiger score to <10 points with a decrease of ≥3 points from baseline improvement in rectal bleeding, and decreased stool frequency to ≤4 per day).	The primary outcome was assessed by the investigator between days 3 and 7, with patients recorded as clinical responders if they had the primary outcome on any day in this assessment window.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
clinical response by day 14	Defined as mayo score decrease of ≥30% and ≥3 points from baseline, accompanied by a decrease in the rectal bleeding subscore of ≥1 point or an absolute rectal bleeding subscore of 0 or 1.	day 14
clinical remission by day 28, day 42, and day 90	Total Mayo score ≤2 points and no individual subscore >1 point.	day 28, day 42, and day 90
Endoscopic response by day 90	A decrease in MES score of ≥1 point, or a decrease of ≥50% from baseline.	day 90
Endoscopic remission by day 90	MES score ≤1	day 90
Endoscopic+clinical response	Partial Mayo score ≤1 and MES ≤1	day 90
Clinical +FcP remission	Partial Mayo score ≤1 and FcP≤250mg/kg	day 90
Clinical +CRP remission	Partial Mayo score ≤1 and CRP≤5mg/L	day 90
Histologic remission	typically defined as the absence of signs of neutrophilic infiltration. The specific criterion is a score below 2B.0, i.e., no increased neutrophils in the lamina propria.	day 90
Histologic improvement	when assessing treatment efficacy, a score ≤ 3.1 (intraepithelial neutrophilic infiltration involving < 50% of crypts) is used as the threshold for histologic improvement.	day 90
Adverse Reactions	Adverse Reactions	day 90
IBDQ and fatigue questionnaire scores	IBDQ and fatigue questionnaire scores	day 0 and day 90

Collaborators and Investigators

• Sponsor: Yongquan Shi

Publications and helpful links

General Publications

• D'Haens G, Lemmens L, Geboes K, Vandeputte L, Van Acker F, Mortelmans L, Peeters M, Vermeire S, Penninckx F, Nevens F, Hiele M, Rutgeerts P. Intravenous cyclosporine versus intravenous corticosteroids as single therapy for severe attacks of ulcerative colitis. Gastroenterology. 2001 May;120(6):1323-9. doi: 10.1053/gast.2001.23983.
• Choy MC, Li Wai Suen CFD, Con D, Boyd K, Pena R, Burrell K, Rosella O, Proud D, Brouwer R, Gorelik A, Liew D, Connell WR, Wright EK, Taylor KM, Pudipeddi A, Sawers M, Christensen B, Ng W, Begun J, Radford-Smith G, Garg M, Martin N, van Langenberg DR, Ding NS, Beswick L, Leong RW, Sparrow MP, De Cruz P. Intensified versus standard dose infliximab induction therapy for steroid-refractory acute severe ulcerative colitis (PREDICT-UC): an open-label, multicentre, randomised controlled trial. Lancet Gastroenterol Hepatol. 2024 Nov;9(11):981-996. doi: 10.1016/S2468-1253(24)00200-0. Epub 2024 Sep 2.

Study record dates

Study Major Dates

• Study Start (Estimated): March 23, 2026
• Primary Completion (Estimated): March 30, 2027
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: March 26, 2026
• First Submitted That Met QC Criteria: April 19, 2026
• First Posted (Actual): April 22, 2026

Study Record Updates

• Last Update Posted (Actual): April 22, 2026
• Last Update Submitted That Met QC Criteria: April 19, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Randomized Controlled Trial; Upadacitinib; Corticosteroids; acute severe ulcerative colitis; First-Line Therapy
• Additional Relevant MeSH Terms: Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; upadacitinib; Adrenal Cortex Hormones
• Other Study ID Numbers: KY20252556-F-1-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No