Combination Therapy With Infliximab and Tofacitinib for Acute Severe Ulcerative Colitis - CINTO Trial

Asian Institute of Gastroenterology, India

Status and phase: Not yet enrolling; Phase 2

Conditions: Acute Severe Ulcerative Colitis

Treatments: Drug: Infliximab; Drug: Tofacitinib

Study type: Interventional

Funder types: Other

Identifiers

NCT07297069

CINTO 1

Details and patient eligibility

About

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

Full description

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.

Enrollment: 60 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Adult (aged 18 years to 65 years) patients hospitalised due to ASUC

Exclusion criteria

1. Patients with UC who did not meet the Truelove Witts criteria for ASUC.
2. Patients who are already on Tofacitinib / Infliximab.
3. Latent or active tuberculosis.
4. Crohn's or Indeterminate colitis.
5. Mega colon (if the diameter of the transverse colon is 5.5 cm or more, with apparent oedema of the bowel wall on plain abdominal radiographs).
6. Pseudomembranous colitis or concomitant CMV colitis.
7. Intestinal perforation.
8. Massive haemorrhage requiring emergency colectomy.
9. Pregnant or lactating female individuals.
10. Current diagnosis or history of thromboembolic disease patients with severe cardiorespiratory, renal or hepatic Co morbidities.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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60 participants in 3 patient groups

Infliximab Plus Tofacitinib

Experimental group

Description:

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.

Treatment:

Drug: Tofacitinib

Drug: Infliximab

Infliximab Only

Active Comparator group

Description:

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.

Treatment:

Drug: Infliximab

Tofacitinib Only

Active Comparator group

Description:

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.

Treatment:

Drug: Tofacitinib