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In adults hospitalized with acute severe ulcerative colitis who fail to respond to intravenous steroids, does treatment with a combination of infliximab and tofacitinib, compared with infliximab alone or tofacitinib alone, result in higher rates of early clinical remission and mucosal healing, and fewer treatment-related complications over a 10 week period
Acute severe ulcerative colitis (ASUC) is a life threatening manifestation of ulcerative colitis that requires urgent medical treatment and hospitalization. Despite the use of rapid induction intravenous corticosteroids, some patients fail to respond and require rescue therapy. Infliximab is commonly used as rescue treatment; however, its effectiveness may be reduced in patients with severe inflammation and hypoalbuminemia. As a result, colectomy rates for ASUC remain significant and improved early rescue strategies are needed.
Tofacitinib is an oral Janus kinase inhibitor that targets multiple cytokine pathways involved in ulcerative colitis. It has a rapid onset of action and has shown benefit in severe and steroid-refractory disease. Because infliximab and tofacitinib act on different immunologic targets, their combined use may provide complementary therapeutic effects. Emerging observational data suggest that combining a biologic agent with a small-molecule therapy may be safe and potentially more effective in patients with severe disease who are at high risk for treatment failure.
This study is designed to explore whether the combination of infliximab and tofacitinib offers greater early clinical benefit compared to infliximab alone, tofacitinib alone for adults hospitalized with ASUC who do not respond to intravenous corticosteroids.The goal is to generate preliminary data that may inform future treatment approaches aimed at improving remission rates, accelerating mucosal healing, and reducing the need for colectomy in this high risk population.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Infliximab Plus Tofacitinib | Experimental | Participants with acute severe ulcerative colitis who do not respond to intravenous corticosteroids will receive combination therapy with infliximab and tofacitinib. Infliximab 300 mg will be given intravenously, and tofacitinib will be administered orally at 10 mg twice daily. This arm evaluates whether combination therapy produces enhanced early clinical improvement and offers greater effectiveness and safety in inducing early clinical remission and mucosal healing compared with either agent alone. |
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| Infliximab Only | Active Comparator | Participants with acute severe ulcerative colitis who do not respond to intravenous corticosteroids will receive infliximab alone as rescue therapy. Infliximab will be administered at a dose of 300 mg intravenously according to protocol. This arm evaluates the effectiveness and safety of infliximab monotherapy in inducing early clinical remission and mucosal healing. |
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| Tofacitinib Only | Active Comparator | Participants with acute severe ulcerative colitis who do not respond to intravenous corticosteroids will receive tofacitinib alone as rescue therapy. Tofacitinib will be administered orally at 10 mg twice daily. This arm assesses the effectiveness and safety of tofacitinib monotherapy in inducing early clinical remission and mucosal healing. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Infliximab | Drug | Participants with acute severe ulcerative colitis who do not respond to intravenous corticosteroids will receive infliximab as rescue therapy. Infliximab 300 mg will be administered intravenously. This arm evaluates the effectiveness and safety of infliximab monotherapy in inducing early clinical remission and mucosal healing. |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical Remission Rate | Clinical remission is defined as defined as a Mayo score ≤2 and no individual subscore >1.Participants meeting these criteria will be classified as achieving clinical remission. | Week 1 and Week 4 |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical Response Rate | Reduction of baseline Mayo score by ≥3 points and a decrease of 30% from the baseline score with a decrease of at least one point on the rectal bleeding subscale or an absolute rectal bleeding score of 0 or 1. | Week 1 and Week 4 |
| Mucosal Healing Rate |
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Inclusion Criteria:
Adult (aged 18 years to 65 years) patients hospitalised due to ASUC
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Vamsi Krishna Ankam, DrNB(medical gastroenterology) | Contact | +91 9705904243 | Vamsiankam999@gmail.com | |
| Pardhu Bharath Neelam, DM (gastroenterology) | Contact | +91 7799456166 | Drpardhu.bharath@gmail.com |
| Name | Affiliation | Role |
|---|---|---|
| Vamsi Krishna Ankam, DrNB(gastroenterology) | Asian Institute of Gastroenterology, Hyderabad | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Asian Institute of Gastroenterology | Hyderabad | Telangana | 500082 | India |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| Background | Hickman K, Jordan R, Sonnier W. Combination biologic and small molecule therapy for refractory ulcerative colitis. Gastroenterology. 2022;162(3 Suppl):S103. | ||
| 36973416 | Background | A genome-scale CRISPR tool for targeting multiple gene family members at once. Nat Plants. 2023 Apr;9(4):511-512. doi: 10.1038/s41477-023-01388-y. No abstract available. |
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Individual participant data (IPD) will not be shared because data sharing is not planned for this study.
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| ID | Term |
|---|---|
| D000069285 | Infliximab |
| C479163 | tofacitinib |
| ID | Term |
|---|---|
| D000911 | Antibodies, Monoclonal |
| D000906 | Antibodies |
| D007136 | Immunoglobulins |
| D007162 | Immunoproteins |
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Three arm parallel randomized pilot trial comparing infliximab alone, tofacitinib alone, and combination therapy with infliximab plus tofacitinib in adults hospitalized with acute severe ulcerative colitis who do not respond to intravenous corticosteroids.
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| Tofacitinib | Drug | Participants with acute severe ulcerative colitis who do not respond to intravenous corticosteroids will receive tofacitinib as rescue therapy. Tofacitinib will be administered orally at 10 mg twice daily. This arm assesses the effectiveness and safety of tofacitinib monotherapy in inducing early clinical remission and mucosal healing. |
|
Mucosal healing is defined as an endoscopic Mayo score of 0 or 1 on flexible sigmoidoscopy. Participants undergoing endoscopic evaluation who meet these criteria will be classified as achieving mucosal healing. |
| Week 4 and Week 12 |
| Treatment Related Adverse Events | Adverse events related to study medications, including but not limited to infections, lymphocytopenia, thromboembolic events, hyperlipidemia, and infusion or drug-related reactions, will be recorded throughout the study period. Severity and relationship to the study intervention will be assessed. | Baseline through Week 12 |
| D001798 |
| Blood Proteins |
| D011506 | Proteins |
| D000602 | Amino Acids, Peptides, and Proteins |
| D012712 | Serum Globulins |
| D005916 | Globulins |