An Active Surveillance, Post-Authorization Study to Characterize the Safety of Tofacitinib in Patients With Moderately to Severely Active Ulcerative Colitis in the Real-World Setting Using Data From the United Registries for Clinical Assessment and Research (UR-CARE) in the European Union (EU) (PASS TOFA)

June 17, 2024 updated by: Grupo Espanol de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa
The purpose of this study is to estimate the incidence rates of malignancy, excluding non-melanoma skin cancer (NMSC), venous thromboembolic events VTE (deep venous thrombosis [DVT] and pulmonary embolism [PE]), NMSC, major adverse cardiac events (MACE), progressive multifocal leukoencephalopathy (PML), infections, hospitalization and specific antibiotic or antiviral treatment, lung cancer, lymphoma, herpes zoster, myocardial infarction (MI), gastrointestinal (GI) perforations, fractures, surgery for UC and death; through 4 sub-groups: adult patients with UC who initiate tofacitinib in the course of routine clinical care compared to other medications approved to treat UC.

Study Overview

Status

Recruiting

Conditions

Detailed Description

Rationale and background:

Tofacitinib, an inhibitor of the Janus kinase (JAK) family of kinases, was approved in the European Union (EU) in July 2018 at a dose of 5 mg twice daily or 10 mg twice daily for the treatment of adults with moderate-to-severe ulcerative colitis (UC), who have had an inadequate response, lost response, or were intolerant to either conventional therapy or a biologic agent. Malignancy excluding non-melanoma skin cancer (NMSC) is an important potential risk and venous thromboembolism (VTE) is an important identified risk associated with the use of tofacitinib, and follow-up of large cohorts of patients over a long period is needed to evaluate the risks of these safety events, as well as other potential safety events of interest, that may be associated with tofacitinib treatment. Pfizer will implement a post approval, active surveillance study of tofacitinib exposed and unexposed patients using actively collected prospective data included in the UR-CARE platform.

Research question:

What are the incidence rates of safety events of interest in adult patients with UC treated with tofacitinib in routine clinical care, as compared to the incidence rates in patients with UC treated with other approved systemic agents, and patients with UC naïve to biologics and immunomodulators/immunosuppressants (hereafter referred to as immunosuppressants)?

Study design:

This is an active cohort study of adult patients with UC aged ≥18 years treated with tofacitinib compared to patient receiving alternative treatment or not treatment. The study will use secondary data collected in the UR-CARE platform, which is an ongoing, prospective, observational, cohort of European Union (EU) patients with inflammatory bowel disease (IBD) with the primary aim of facilitating daily patient care and research studies in IBD. This study will focus only on patients with UC enrolled in the UR-CARE platform.

Variables:

The study variables include baseline patient characteristics (i.e., clinical and demographic characteristics, comorbidities, and current and past therapies), the primary outcomes of interest, and other safety events of interest.

Data sources:UR-CARE will be used as the only data source.

Study size:

This study is descriptive, and all eligible patients in UR-CARE registry during the study period who have consented to participate in the study will be included, with no upper limit on the sample size.

Data analysis:

All statistical analysis will be performed by GETECCU using SAS software v9.4, SAS Institute Inc, Cary, NC, USA. Detailed methodology for summary and statistical analyses of data collected in this study will be documented in a statistical analysis plan (SAP).

Study Type

Observational

Enrollment (Estimated)

104

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

Adult patients with UC aged ≥18 years treated with tofacitinib compared to patient receiving alternative treatment or not treatment. The study will use secondary data collected in the UR-CARE platform, which is an ongoing, prospective, observational, cohort of European Union (EU) patients with inflammatory bowel disease (IBD) with the primary aim of facilitating daily patient care and research studies in IBD. This study will focus only on patients with UC enrolled in the UR-CARE platform.

Description

Inclusion Criteria:

  • Adult patients aged ≥18 years,
  • With Ulcerative colitis diagnosis per ECCO guidelines,
  • Enrolled in UR-CARE registry with 12 months of medical history available in UR-CARE prior to the index date,
  • With an informed consent signed. A minimum follow-up duration of 12 months will allow evaluation of safety events of interest.

Exclusion Criteria:

  • Patients not meeting the inclusion criteria
  • Patients who have any records of Crohn's Diseases (CD) or IBD unspecified in UR-CARE between the last UC diagnosis and index date [i.e. date of first prescription for tofacitinib].

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Cohorts and Interventions

Group / Cohort
Cohort 1 (Tofacitinib cohort):
Initiation of tofacitinib (i.e., first ever prescription) from 01 July 2018 through to 31 March 2025
Cohort 2 (Biologics cohort):
  • Initiation (i.e., first ever prescription) of a specific biologic agent (any TNFi or non-TNFi agent) from 01 July 2018 through to 31 March 2025
  • No prior use of specific biologic agent prior to index date using all available data
Cohort 3 (Immunosuppressants cohort):
  • Initiation (i.e., first ever prescription) of a specific immunosuppressant agent (without concurrent biologic therapy) from 01 July 2018 through to 31 March 2025
  • No prior use of specific immunosuppressant prior to index date using all available data
Cohort 4 (Naïve cohort):
  • Patients diagnosed with UC since 01 July 2018 through to 31 March 2025
  • Patients with no history of surgery for UC (surgery suggests more severe disease, and such patients would not be representative of patients with generally mild disease in Cohort 4)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Malignancy excluding non-melanoma skin cancer (NMSC)
Time Frame: from 01 July 2018 through to 31 March 2025
Malignancy excluding non-melanoma skin cancer (NMSC). As this is a post-authorisation safety study requested by the EMA, the physician is simply asked to report whether such an event has occurred in the patient's life and under what treatment. The study does not aim to measure or clinically qualify this event, which is why nothing more is asked to estimate the incidence rates of the event.
from 01 July 2018 through to 31 March 2025
venous thromboembolic events (VTE),(deep venous thrombosis [DVT] and pulmonary embolism [PE])
Time Frame: from 01 July 2018 through to 31 March 2025
deep venous thrombosis [DVT] and pulmonary embolism [PE]. As this is a post-authorisation safety study requested by the EMA, the physician is simply asked to report whether such an event has occurred in the patient's life and under what treatment. The study does not aim to measure or clinically qualify this event, which is why nothing more is asked to estimate the incidence rates of the event.
from 01 July 2018 through to 31 March 2025

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Non melanoma skin cancer (NMSC)
Time Frame: from 01 July 2018 through to 31 March 2025
Non melanoma skin cancer (NMSC). As this is a post-authorisation safety study requested by the EMA, the physician is simply asked to report whether such an event has occurred in the patient's life and under what treatment. The study does not aim to measure or clinically qualify this event, which is why nothing more is asked to estimate the incidence rates of the event.
from 01 July 2018 through to 31 March 2025
Lung cancer
Time Frame: from 01 July 2018 through to 31 March 2025
Lung cancer. As this is a post-authorisation safety study requested by the EMA, the physician is simply asked to report whether such an event has occurred in the patient's life and under what treatment. The study does not aim to measure or clinically qualify this event, which is why nothing more is asked to estimate the incidence rates of the event.
from 01 July 2018 through to 31 March 2025
Lymphoma
Time Frame: from 01 July 2018 through to 31 March 2025

Lymphoma (including 3 main subtypes Hodgkin's lymphoma, non-Hodgkin's lymphoma, and chronic lymphocytic lymphoma).

As this is a post-authorisation safety study requested by the EMA, the physician is simply asked to report whether such an event has occurred in the patient's life and under what treatment. The study does not aim to measure or clinically qualify this event, which is why nothing more is asked to estimate the incidence rates of the event.
from 01 July 2018 through to 31 March 2025
Serious infections
Time Frame: from 01 July 2018 through to 31 March 2025
Serious infections. As this is a post-authorisation safety study requested by the EMA, the physician is simply asked to report whether such an event has occurred in the patient's life and under what treatment. The study does not aim to measure or clinically qualify this event, which is why nothing more is asked to estimate the incidence rates of the event.
from 01 July 2018 through to 31 March 2025
Opportunistic infections (e.g., tuberculosis)
Time Frame: from 01 July 2018 through to 31 March 2025
Opportunistic infections (e.g., tuberculosis). As this is a post-authorisation safety study requested by the EMA, the physician is simply asked to report whether such an event has occurred in the patient's life and under what treatment. The study does not aim to measure or clinically qualify this event, which is why nothing more is asked to estimate the incidence rates of the event.
from 01 July 2018 through to 31 March 2025
Herpes zoster(HZ)
Time Frame: from 01 July 2018 through to 31 March 2025
Herpes zoster(HZ). As this is a post-authorisation safety study requested by the EMA, the physician is simply asked to report whether such an event has occurred in the patient's life and under what treatment. The study does not aim to measure or clinically qualify this event, which is why nothing more is asked to estimate the incidence rates of the event.
from 01 July 2018 through to 31 March 2025
Major adverse cardiac events (MACE)
Time Frame: from 01 July 2018 through to 31 March 2025
Major adverse cardiac events (MACE)
from 01 July 2018 through to 31 March 2025
Myocardial infarction (MI)
Time Frame: from 01 July 2018 through to 31 March 2025
Myocardial infarction (MI). As this is a post-authorisation safety study requested by the EMA, the physician is simply asked to report whether such an event has occurred in the patient's life and under what treatment. The study does not aim to measure or clinically qualify this event, which is why nothing more is asked to estimate the incidence rates of the event.
from 01 July 2018 through to 31 March 2025
Progressive multifocal leukoencephalopathy (PML)
Time Frame: from 01 July 2018 through to 31 March 2025
Progressive multifocal leukoencephalopathy (PML). As this is a post-authorisation safety study requested by the EMA, the physician is simply asked to report whether such an event has occurred in the patient's life and under what treatment. The study does not aim to measure or clinically qualify this event, which is why nothing more is asked to estimate the incidence rates of the event.
from 01 July 2018 through to 31 March 2025
Gastrointestinal (GI) perforations
Time Frame: from 01 July 2018 through to 31 March 2025
Gastrointestinal (GI) perforations. As this is a post-authorisation safety study requested by the EMA, the physician is simply asked to report whether such an event has occurred in the patient's life and under what treatment. The study does not aim to measure or clinically qualify this event, which is why nothing more is asked to estimate the incidence rates of the event.
from 01 July 2018 through to 31 March 2025
Fractures
Time Frame: from 01 July 2018 through to 31 March 2025
Fractures. As this is a post-authorisation safety study requested by the EMA, the physician is simply asked to report whether such an event has occurred in the patient's life and under what treatment. The study does not aim to measure or clinically qualify this event, which is why nothing more is asked to estimate the incidence rates of the event.
from 01 July 2018 through to 31 March 2025
All-cause mortality
Time Frame: from 01 July 2018 through to 31 March 2025
All-cause mortality
from 01 July 2018 through to 31 March 2025
surgery for Ulcerative colitis (UC)
Time Frame: from 01 July 2018 through to 31 March 2025
surgery for Ulcerative colitis (UC). As this is a post-authorisation safety study requested by the EMA, the physician is simply asked to report whether such an event has occurred in the patient's life and under what treatment. The study does not aim to measure or clinically qualify this event, which is why nothing more is asked to estimate the incidence rates of the event.
from 01 July 2018 through to 31 March 2025

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Grupo Espanol de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa

Collaborators

Pfizer

Investigators

  • Principal Investigator: Manuel MD Barreiro, PhD, Grupo Espanol de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 11, 2024

Primary Completion (Estimated)

March 31, 2025

Study Completion (Estimated)

March 31, 2026

Study Registration Dates

First Submitted

June 7, 2024

First Submitted That Met QC Criteria

June 17, 2024

First Posted (Actual)

June 21, 2024

Study Record Updates

Last Update Posted (Actual)

June 21, 2024

Last Update Submitted That Met QC Criteria

June 17, 2024

Last Verified

June 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PASS TOFA

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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