Clinical trial NCT06786507: A Direct Head-to-head Comparison of Ustekinumab with Infliximab for the Treatment of Ulcerative Colitis
Official title: A Direct Head-to-head Comparison of Ustekinumab with Infliximab for the Treatment of Ulcerative Colitis
Study type: OBSERVATIONAL
Overall status: NOT_YET_RECRUITING
Conditions: Ulcerative Colitis (UC)
Lead sponsor: Helwan University
Sponsor class: OTHER
First posted: 2025-01-22
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: moderate to severe ulcerative colitis bio naïve patients

Brief summary: the goal of this study is to compare the efficacy of ustekinumab with infliximab for the treatment of ulcerative colitis aim of the study :

1. Compare effectiveness of ustekinumab versus infliximab therapy in remission achievement in UC patients.
2. Compare safety of ustekinumab therapy versus infliximab therapy in UC
3. To asses quality of life of ustekinumab therapy versus infliximab therapy in UC patients.

Detailed description: Inflammatory bowel disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), is a chronic inflammatory relapsing disorder affecting the gastrointestinal tract and is characterized by a progressive and unpredictable disease course.. The major subtypes are :

1. Crohn's Disease which affects any part of GIT.
2. Ulcerative Colitis which affects mainly the colon . And a subtype of IBD is called intermediate colitis (IC) when its unable to diffrentiate between UC and Crohns disease . There has been a global rise in the incidence of IBD over the last few decades, in 2017; there were 6.8 million cases of IBD globally. The age-standardized prevalence rate increased from 79.5 per 100, 000 population in 1990 to 84.3 per 100, 000 population in 2017. The annual incidence of Crohn's disease is 5.0 per 100,000 person-years in Asia and the Middle East, whereas incidence rates of ulcerative colitis are 6.3 per 100,000 person-years in Asia and the Middle East . some studies suggest the relative incidence ratio of UC and CD is 6:1 .Regarding UC the highest incidence of the disease is in Northern Europe and Canada at 24.3 and 19.2/100,000, respectively. Prevalence rates are also the highest in these two regions, at 505/100,000 in Northern Europe and 248/100,000 in Canada with incidence rate of 2.33 per 100,000 persons per year for UC in the Arab world Ulcerative colitis (UC) is a chronic, idiopathic inflammatory condition that affects the mucosa of the colon and rectum. Ulcerative colitis is also considered a progressive disease as it is associated with increased risk of disease extension, dysplasia/neoplasia, fibrosis and rectal dysfunction. Observational studies suggest that one-third of patients with left-sided colitis or disease limited to the rectum will develop pancolitis over a period of 10 years .

The changing epidemiology and the progressive nature of the disease require a clear understanding of the available and soon to become available therapeutic agents to treat UC and the different aspects of their pharmacology .

Treatments for inducing remission include 5-aminosalicylic acid drugs and corticosteroids. Maintenance treatments include 5-aminosalicylic acid drugs, thiopurines, biologics (eg,anti TNF , anti-cytokines and anti-integrins), and small molecules (Janus kinase inhibitors and sphingosine-1-phosphate receptor modulators) .

Infliximab is a biological therapy/immunotherapy medication designed to stimulate the body's immune system and treat certain diseases. Infliximab is a purified, recombinant DNA-derived chimeric IgG monoclonal antibody protein that contains both murine and human components that inhibit tumor necrosis factor-alpha (TNF-α). TNF-α is a signaling protein involved in acute phase reactions and systemic inflammation. Macrophages, CD4+ lymphocytes, NK cells, neutrophils, mast cells, eosinophils, and neurons produce TNF-α. This TNF-α inhibition inhibits the inflammatory reaction's cascade, leading to improved disease condition inflammatory bowel disease .

Infliximab has a high affinity for TNF-α and does not inhibit TNF-β. TNF-α is responsible for several physiological responses, including inducing proinflammatory cytokines (eg, IL-1 and IL-6), increasing adhesion molecule release, and enhancing the migration of leukocytes from blood vessels in the surrounding tissue (via increased endothelial permeability) . Infliximab is administered in dose 5 mg/kg i.v. for the whole induction and maintenance phase .

Ustekinumab is a human monoclonal IgG1 antibody that blocks the p40 subunit of both IL-12 and IL-23 this antagonistic action inhibits the interaction of these cytokines with the IL-12Rβ1 receptor. The IL-12Rβ1 receptor is found on the surface of NK cells and T cells which reduces inflammation and alters the body's immune response . ulcerative colitis treatment is based on an initial intravenous weight-based infusion followed by a subcutaneous maintenance schedule (90 mg subcutaneously eight weeks after initial intravenous administration and every eight weeks after that) .

The prognosis in UC is difficult to assess, however it should be emphasized that even one-third of patients need to undergo surgical treatment (colectomy) at different stages of the disease. Due to these data, together with the fact of increasing prevalence of UC reported in many industrialized and developing countries .

several treatment options now are available for the management of moderate-severe ulcerative colitis, with variable efficacy and safety profiles, and positioning different agents in the treatment course as first-line (in biologic-naïve patients) and second-line (in patients with prior exposure to tumor necrosis factor \[TNF\]-α antagonists) is a key knowledge gap. In the absence of head-to-head comparisons, prior network meta-analyses have attempted to address this gap, but have been limited by the number of studies especially at Egyptian population , that why this study will be conducted .

Eligibility criteria: Inclusion Criteria:

* Subjects who are voluntarily able to give informed consent
* Subjects who can participate in all aspects of this clinical study
* Males and females aged from ≥ 18 to ≤ 80 years, at screening visit
* Diagnosis of moderate to severe UC established by clinical and endoscopic evidence.
* Biological therapy naïve patients.

Exclusion Criteria:

* - Previous exposure to IFX or UST or any other in IFX or UST-containing product
* Has a history of hypersensitivity or allergies to the ingredients of IFX or UST formulations
* Unstable angina
* Moderate or severe heart failure (defined as New York Heart Association Class III or IV)
* Chronic respiratory failure
* History of any major neurological disorders including stroke, multiple sclerosis, brain tumor, or neurodegenerative disease
* Chronic hepatitis B or C infection. Patients with positive viral serology at screening for infection with hepatitis B (HBV) or hepatitis C virus (HCV) may be eligible if the polymerase chain reaction test is negative, and the patients receive standard of-care antiviral prophylaxis (if applicable)
* Known severe chronic kidney failure
* Known severe chronic liver failure
* Known active or latent tuberculosis
* Ongoing HIV infection

Primary outcomes:
measure: (CRP) and Improvement degree of ulcerative colitis
timeFrame: baseline and after 6 months
measure: safety evaluation
timeFrame: baseline and after 6 months
Secondary outcomes:
measure: improvement in quality of life
timeFrame: baseline and after 6 months
Other outcomes:
Locations:
city: Cairo
country: Egypt
facility: El-Demerdash hospital
Study officials:
References: