Ulcerative ColitisNCT05728008
Retrospective Observational Comparison Study Between Ustekinumab and Tofacitinib as Third Line Therapy in a Multicenter Cohort of Patients With Refractory Ulcerative Colitis.
An observational study of Ulcerative Colitis, run by IRCCS San Raffaele at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ulcerative Colitis
- What is being tested?
- Ustekinumab and Tofacitinib
- Type of treatment
- Injection or infusion
- How many people
- 100 participants
- Where
- 1 siteItaly
- Study dates
- 5 Apr 2022to 5 Jul 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- Patients with unclassified colitis or Crohn disease
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the detailed description
This is an observational, retrospective, international multicenter study on the comparison of ustekinumab (anti-IL12-23) and tofacitinib (pan JAK inhibitor) used as third-line therapy in UC cases.
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.
Subjects received the drugs, as per clinical practice, starting from their marketing authorization up to February 2022. The data will be collected starting from the time of diagnosis of UC up to last follow-up. This study does not require specific procedures as it is intended for the collection and analysis of data from treatments already carried out.
- Conditions
- Ulcerative Colitis
- Being tested
- Ustekinumab, Tofacitinib
- Medical subject headings
- Colitis, Ulcerative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UstekinumabDrug
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.
TofacitinibDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| 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 Receives: 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. Receives: Drug: Tofacitinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 months
Secondary outcomes (1)
IBD outcomes
- hospitalization rate (e.g. hospitalization, admission to intensive care unit)
- surgery rate (type of surgery, occurrence colorectal dysplasia and/or colorectal cancer)
- drug optimization rate (start of systemic steroids, immunosuppressants, or biologics, dose optimization, interval optimization), switch to another drug, or swap to another drug
- drug discontinuation rate alone (need to switch or to swap to another drug)
Measured: 2 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Feb 2023
- Study start5 Apr 2022
- Primary completion5 Jun 2022
- Study completion5 Jul 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Ulcerative ColitisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 100 participants (actual)
Sponsor and investigators
- Lead sponsor
- IRCCS San Raffaele
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Mariangela Allocca, IRCCS San Raffaele
- Investigators
- MARIANGELA ALLOCCA, Principal investigator, IRCCS San Raffaele
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05728008
- Sponsor's protocol ID
- UST-TOFA3
- Status last verified
- Jan 2023
- First submitted
- 30 Jan 2023
- Last updated
- 14 Feb 2023
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Feb 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Retrospective Observational Comparison Study Between Ustekinumab and Tofacitinib as Third Line Therapy in a Multicenter Cohort of Patients With Refractory Ulcerative Colitis.
- ClinicalTrials.gov ID
- NCT05728008
- Acronym / sponsor ID
- UST-TOFA3
- Conditions
- Ulcerative Colitis
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 100 participants (actual)
- Lead sponsor
- IRCCS San RaffaeleUniversity, hospital or other
- Study start
- 5 Apr 2022 (actual)
- Primary completion
- 5 Jun 2022 (actual)
- Study completion
- 5 Jul 2022 (actual)
- First posted
- 14 Feb 2023 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
This is an observational, retrospective, international multicenter study on the comparison of ustekinumab (anti-IL12-23) and tofacitinib (pan JAK inhibitor) used as third-line therapy in UC cases.
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.
Subjects received the drugs, as per clinical practice, starting from their marketing authorization up to February 2022. The data will be collected starting from the time of diagnosis of UC up to last follow-up. This study does not require specific procedures as it is intended for the collection and analysis of data from treatments already carried out.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| subject treated with ustekinumab (anti-IL12-23) | – | Drug: Ustekinumabsubjects treated with ustekinumab (anti-IL12-23) and have a follow-up at 24 +/- 4 weeks from the start of the third line therapy |
| subject treated withtofacitinib (pan JAK inhibitor) | – | Drug: Tofacitinibsubjects treated with tofacitinib (pan JAK inhibitor) and have a follow-up at 24 +/- 4 weeks from the start of the third line therapy. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (1 listed)
- Patients with unclassified colitis or Crohn disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ustekinumaba 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. | Drug | subject treated with ustekinumab (anti-IL12-23) |
| TofacitinibJak 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. | Drug | subject treated withtofacitinib (pan JAK inhibitor) |
Primary outcome
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.
Time frame: 2 months
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.
1 secondary outcome
IBD outcomes
Time frame: 2 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Feb 2023.
Related trials for Ulcerative Colitis
Active, not recruitingObservational study
A Study to Learn About the Effectiveness of Etrasimod in People With Ulcerative Colitis
Colitis, Ulcerative
RecruitingPhase 1/2
Study of XmAb942 in Healthy Participants and Participants With Ulcerative Colitis
Ulcerative Colitis (UC)
RecruitingPhase 3
Extension Study of Long-term Safety and Efficacy of Tulisokibart in Participants With Crohn's Disease or Ulcerative Colitis (MK-7240-011)
Crohn Disease, Colitis, Ulcerative
RecruitingObservational study
ALPCO Calprotectin CLIA Assay - Measurement of Calprotectin Levels in Human Stool
Inflammatory Bowel Disease (Crohn's Disease and Ulcerative Colitis), Inflammatory Bowel Syndrome
RecruitingObservational study
Longitudinal Immunophenotyping of Patients With Inflammatory Bowel Disease
Inflammatory Bowel Disease, Crohn's Disease
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
MARIANGELA ALLOCCA principal investigator
IRCCS San Raffaele
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Ulcerative Colitis, run by IRCCS San Raffaele at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 14 Feb 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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. (time frame: 2 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Feb 2023; AzTrials last refreshed its copy on 31 Oct 2026.