臨床研究等提出・公開システム

Open-ravel randomized control trial to evaluate the efficacy of biologics for ulcerative colitis with treatment-refractoriness

UC Bio Study

105

The baseline characteristics for the full analysis set (FAS) population were as follows. [Infliximab treatment group] n = 33 Sex, male 24 (72.7%) / female 9 (27.3%) Age, 38.9 +- 12.5 years (mean +- SD) duration of disease, 2.9 years (median) [Ustekinumab treatment group] n = 30 Sex, male 17 (56.7%) / female 13 (43.3%) Age, 45.2 +- 18.1 years (mean +- SD) duration of disease, 6.0 years (median) [Vedolizumab treatment group] n = 34 Sex, male 20 (58.8%) / female 14 (41.2%) Age, 52.0 +- 18.6 years (mean +- SD) duration of disease, 2.6 years (median)

One-hundred seven subjects were enrolled and randomized on EDC (Electronic Data Capture) between May 2021 and June 2023, but the actual number of participants, excluding 2 erroneous enrollments, were 105(35 subjects were to the infliximab group, 34 to the ustekinumab group, and 36 to the vedolizumab group. A total of 104 subjects, 34 in the infliximab group, 34 in the ustekinumab group, and 36 in the vedolizumab group started treatment with the study drug. There were 88 subjects who completed 12 weeks (28 in the infliximab group, 30 in the ustekinumab group, and 30 in the vedolizumab group), 66 subjects completed 26 weeks (17 in the infliximab group, 28 in the ustekinumab group, and 21 in the vedolizumab group). The safety population included 104 subjects, 34 in the infliximab group, 34 in the ustekinumab group, and 36 in the vedolizumab group, and the FAS population included 97 subjects, 33 in the infliximab group, 30 in the ustekinumab group, and 34 in the vedolizumab group.

In this study, adverse events were reported in 11/34 subjects (32.4%) in the infliximab group, 13/36 subjects (36.1%) in the vedolizumab group, and 3/34 subjects (8.8%) in the ustekinumab group. In addition, adverse drug reactions were reported in 5/34 subjects (14.7%) in the infliximab group, 6/36 subjects (16.7%) in the vedolizumab group, and 2/34 subjects (5.9%) in the ustekinumab group. Serious adverse events showed in 1/34 subject (2.9%) in the infliximab group and 2/36 subjects (5.6%) in the vedolizumab group, and serious adverse drug reactions showed in 1 subject each in the infliximab group and vedolizumab group. No deaths were reported during the study.

The results in the FAS population (97 subjects) were as follows. The primary efficacy endpoint, clinical remission rates at week 12, were 36.4 (95% confidence interval [95%CI], 20.4 to 54.9)% in the infliximab group, 43.3 (95%CI, 25.5 to 62.6)% in the ustekinumab group, 32.4 (95%CI, 17.4 to 50.5)% in the vedolizumab group, and the remission rate was higher in the ustekinumab group than in the other treatment groups. But no statistically significant difference in remission rates was found between treatment groups (infliximab vs. ustekinumab P = 0.5726, infliximab vs. vedolizumab P = 0.7297, ustekinumab vs. vedolizumab P = 0.3665: Wald test.). Therefore, we didn't confirm the clear differences between treatment groups about the clinical remission rate at week 12. Because the superiority of infliximab over ustekinumab and of infliximab over vedolizumab in the primary endpoint was rejected, we didn't perform statistical tests for the secondary endpoints. Although the ustekinumab group outperformed the other treatment groups in some areas, such as the efficacy rate at week 12 and the endoscopic remission rate at week 12, overall, there were no major differences in the results between the treatment groups.

Although the clinical remission rate at week 12, the primary endpoint, was higher in the ustekinumab group than those of the other treatment groups, comparison of the groups showed no statistically significant differences between infliximab, ustekinumab, and vedolizumab. Therefore, in the efficacy evaluation, the inferiority of ustekinumab and vedolizumab to infliximab, the anti-TNF-alpha drug was not verified. In safety, no new adverse events or adverse drug reactions requiring confirmation were reported.

May. 31, 2025

No

N/A

https://jrct.mhlw.go.jp/latest-detail/jRCT1031200329

Naganuma Makoto

Kansai Medical University Hospital

2-3-1, Shinmachi, Hirakata, Osaka

naganuma@hirakata.kmu.ac.jp

Naganuma Makoto

Kansai Medical University Hospital

2-3-1, Shinmachi, Hirakata, Osaka

+81-72-804-2521

naganuma@hirakata.kmu.ac.jp

Complete

Jan. 28, 2021

Interventional

randomized controlled trial

open(masking not used)

active control

parallel assignment

treatment purpose

1) Patients who meet the criteria of the ulcerative colitis diagnostic criteria (revised in 2018) of the Ministry of Health, Labor and Welfare Specified Disease or Intractable Inflammatory Intestinal Disorders Research Group
2) Patients with steroid resistance / dependence at the time of registration or who have previously received systemic steroids
3) Patients who have never used antiTNFa antibody preparations, ustekinumab, or vedolizumab
4) Patients with a Mayo score of 6 points or higher and an endoscopic Mayo score of 2 or higher at the time of registration (Endoscopic scores at the enrollment were assessed by local institutional endoscopists)
5) Patients who are 16 years of age or older at the time of obtaining consent and who have obtained written consent from the patient. For patients with age of 16-19, patients who have obtained the written consent of the person and the substitute
6) Those who have received sufficient explanation before participating in this study, and who have obtained the document for contents after sufficient explanations. For minors, those who have obtained the written consent of the person and the substitute
Definition of steroid resistance The failure to respond to systemic steroid treatment at a dose of 1 to 1.5mg per kg per day for 1 week.
Definition of steroid dependence Either an inability to reduce steroids below the equivalent dose of prednisolone 10 mg per day within 3 months of starting steroid therapy without recurrent active disease, or relapse within 3 months of cessation of steroid therapy.

1) Patients classified as fulminant in the clinical severity classification
2) Patients who are suspected of having colitis rather than ulcerative colitis (infectious enteritis, etc.)
3) Patients with symptomatic gastrointestinal stricture
4) Patients who areplanning colectomy for UC
5) Pregnant women or patients who may be pregnant, lactating patients or those who wish to become pregnant during the study period
6) Patients with contraindications to use infliximab, ustekinumab, or vedolizumab in the package insert
7) Patients who the doctor in charge deems inappropriate to be included in this study
8) Patients participating in clinical trials of other medications
9) Excluding criteria for concomitant medication as below;
1 Patients who have increased the dose of oral 5-aminosalicylic acid within 2 weeks before the registration.
2 Patients who have newly started the enema or suppository treatment with 5-aminosalicylic acid or steroids within 1 week before the registration.
3 Patients receiving oral prednisolone (or equivalent corticosteroid) or intravenous corticosteroid in excess of 30 mg /day within 2 weeks before the registration. In addition, patients who are receiving 30mg daily dose or less of oral or intravenous corticosteroids and whose dosage is not constant within 2 weeks.
4 Patients who newly started thiopurine (azathioprine / 6-mercaptopurine) within 8 weeks before the registration. Patients whose dose of thiopurine was changed within 2 weeks before registration in patients who already received thiopurine.
5 Patients receiving cyclosporine or tacrolimus within 4 weeks before the registration.
6 Patients receiving carotegrastmethyl,upadacitinib,filgotinib or tofacitinib within a week before the registration.
7 Patients receiving apheresis therapy within 4 weeks before the registration. tofacitinib

Both

Ulcerative colitis

Infliximab:Infliximab (5 mg / kg / body weight) is infused intravenously at 0, 2, 6, 14, and 22 weeks.
Vedolizumab:Intravenous infusion of vedolizumab 300 mg at 0, 2, 6, 14, and 22 weeks
Ustekinumab: a single intravenous infusion of the dose shown below is given at the first induction therapy.
Body weight dose
55kg or less 260mg
55-85kg 390mg
85kg or more 520mg

After 8_weeks of intravenous drip infusion, 90 mg of ustekinumab is usually subcutaneously administered to adults, and 90 mg is subcutaneously administered at 12-week intervals thereafter. If the effect is diminished, the dosing interval can be shortened to 8 weeks.

Biologics

D003093

Clinical remission rate at Week 12

1 Clinical response rate at Week 12
2 Endoscopic remission rate at Week 12
3 Complete endoscopic remission at Week12
4 Histological remission at Week 12
5 The rate of fecal calprotectin level less than 150ng/g at Week 12
6 Clinical remission rate at Week 2
7 The rate of no appearance of blood in stool at Week 12
8 Significance of Patients report outcome from Week 0 to Week 2 and Week 12
9 Significance of Mayo subscore (blood in stool) from Week 0 to Week 2 and Week 12
10 Significance of Mayo subscore (number of daily stool) from Week 0 to Week 2 and Week 12
11 Significance of Mayo endoscopic subscore from Week 0 to Week 12
12 Significance of fecal calprotectin level from Week 0 to Week 12

+81-3-5803-4575

Dec. 18, 2020

none