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)

Grupo Espanol de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa104 enrolled

Overview

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.

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).

Outcomes

Primary Outcomes

Malignancy excluding non-melanoma skin cancer (NMSC)

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.