Retrospective Observational Comparison Study Between Ustekinumab and Tofacitinib as Third Line Therapy in a Multicenter Cohort of Patients With Refractory Ulcerative Colitis.

NCT05728008 | Completed

• 1 other identifier: UST-TOFA3
• Study Type: observational
• Target: 100
• Locations: 1 country
• Sites: 1

Brief Summary

Ulcerative colitis (UC) is a chronic remitting and relapsing inflammatory bowel disease. The pathogenesis is multifactorial, involving genetic predisposition, epithelial barrier defects, dysregulated immune responses, and environmental factors. It is diagnosed through colonoscopy and histological evidence of mucosal inflammation involving predominantly the rectum and potentially extending continuously up to the proximal segments of the colon. The patients affected present with severe abdominal pain, bloody diarrhea together with extraintestinal manifestations such as peripheral arthritis, pyoderma gangrenosum, erythema nodosum, ankylosing spondylitis and many others. The last 20 years have been profitable from the therapeutical point of view thanks to the advent of biological drugs which are derived from a living organism or its products including antibodies, interleukins and other molecules capable to target specific cellular pathways and to modulate different mechanisms such as blocking the actions of cytokines or white cells movement in the gut. More recently new promising alternatives seems to be the so-called small molecule drugs which are chemically derived low molecular weight compounds capable to enter the cell to regulate its functions and more generally biological processes like inflammation. In the last years, the therapeutic offer for ulcerative colitis patients has been enriched with the advent of biologics with different mechanism of action and very recently with the availability of the small molecules. Currently the available therapeutic options for ulcerative colitis include topic and systemic mesalazine, topic and systemic glucocorticoids, immunosuppressants (thiopurines), biological drugs (anti-tumor necrosis factor α (TNFα), inhibitor of α4β7 integrin, anti-IL12-23) and small molecules (JAK inhibitors). However, if on the one hand the therapeutical enrichment has clearly improved the disease rate control, still there is the need to perform sequencing study to stratify the available options to provide the best and most appropriate patient-oriented management.

Conditions

Ulcerative Colitis

Outcome Measures

Primary Outcomes (1)

• Determine which drug between ustekinumab and tofacitinib as a third-line treatment, in cases refractory to both anti-TNFα and vedolizumab, is the best option to achieve disease control in terms of hospitalization rate, surgery rate, drug optimization.

  The aim of this retrospective multicentric observational study is to determine which between ustekinumab (anti-IL12-23) and tofacitinib (pan JAK inhibitor) as third-line therapy in UC cases refractory to both anti-TNFα and vedolizumab (inhibitor of α4β7 integrin) is the best compound to achieve disease control.The primary goal is to compare the hospitalization rate, surgery rate, drug optimization rate and the drug discontinuation rate, as a composite primary objective, in patients on either of the two drugs. The induction phase of Ustekinumab consists of approximately 6mg/kg intravenous dose administration. After the induction, the maintenance phase consists of a 90mg subcutaneous dose every 8 weeks. The induction phase of Tofacitinib consists of 10mg twice daily for 8 to 16 weeks. After the induction, the maintenance phase consists of 5mg x twice daily.

  2 months

Secondary Outcomes (1)

• IBD outcomes

  2 months

Study Arms (2)

subject treated with ustekinumab (anti-IL12-23)

subjects treated with ustekinumab (anti-IL12-23) and have a follow-up at 24 +/- 4 weeks from the start of the third line therapy

Drug: Ustekinumab

subject treated withtofacitinib (pan JAK inhibitor)

subjects treated with tofacitinib (pan JAK inhibitor) and have a follow-up at 24 +/- 4 weeks from the start of the third line therapy.

Drug: Tofacitinib

Interventions

Ustekinumab DRUG

a human monoclonal antibody to interleukin IL 12/23 p40. It is indicated in the treatment of adult patients with moderately to severely active UC. The induction phase consists of approximately 6 mg/kg intravenous dose administration. After the induction, the maintenance phase consists of a 90mg subcutaneous dose every 8 weeks.

subject treated with ustekinumab (anti-IL12-23)

Tofacitinib DRUG

Jak inhibitor. It is indicated in the treatment of adult patients with moderately to severely active UC who have experienced inadequate response or have lost the response or who are intolerant to conventional therapy or to a biological agent. The induction phase consists of 10mg twice daily for 8 to 16 weeks. After the induction, the maintenance phase consists of 5mg x twice daily.

subject treated withtofacitinib (pan JAK inhibitor)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Approximately 100 patients with a diagnosis of UC, defined according to ECCO standard of care and who have been treated with ustekinumab (anti-IL12-23) or tofacitinib (pan JAK inhibitor) and have a follow-up at 24 +/- 4 weeks from the start of the third line therapy. Patients will be enrolled from all the 17 centers participating to this international multicenter study Patients will be managed in each IBD center according to standard of care. All centers will be asked to fill the case report form (CRF) with all patients' data.

You may qualify if:

• Age ≥18 years;
• Established diagnosis of UC, defined according to ECCO standard of care
• Documented failure to both anti-TNFα (irrespectively of the number) and vedolizumab
• Ustekinumab or tofacitinib as third-line therapy
• Last follow-up at 24 +/-4 weeks from the start of Ustekinumab or tofacitinib

You may not qualify if:

• Patients with unclassified colitis or Crohn disease

Sponsors & Collaborators

• IRCCS San Raffaele: lead

Study Sites (1)

Mariangela Allocca

Milan, 20132, Italy

Location

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

Ustekinumab; tofacitinib

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• MARIANGELA ALLOCCA

  IRCCS San Raffaele

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Gastroenterologist

Study Record Dates

• First Submitted: January 30, 2023
• First Posted: February 14, 2023
• Study Start: April 5, 2022
• Primary Completion: June 5, 2022
• Study Completion: July 5, 2022
• Last Updated: February 14, 2023

Record last verified: 2023-01

Locations

IT (1)