Tofacitinib Response in Ulcerative Colitis - a Real World Prospective Multi-center Study

Terminated

• Conditions: Ulcerative Colitis

• Registration Number: NCT03772145
• Lead Sponsor: University of North Carolina, Chapel Hill

Brief Summary

The overarching goal of this study, is to create a longitudinally followed, well phenotyped cohort of patients with UC starting treatment with tofacitinib in the setting of standard of care who have linked clinical data and self-reported outcome data that will lead to evaluation of efficacy and safety of tofacitinib in the real-life setting. The specific aims for the study are:

1. Create a prospective cohort of well phenotyped (proctitis vs. rectosigmoiditis vs. extensive) adult UC patients with serial clinical and patient-reported data collected throughout the course of 12 months of tofacitinib therapy. Enrolled patients on therapy will be followed up to 36 months after the start of therapy.

2. To determine clinical response rates and persistence of therapy with tofacitinib for induction and maintenance therapy

3. Describe the incidence of specific drug-associated adverse events (shingles, serious infections), hospitalizations and surgeries in the standard of care setting.

4. Assess the correlation of various outcome measures in ulcerative colitis (Simple Clinical Colitis Activity Index (SCCAI), partial Mayo index, 6-point index) and endoscopic outcomes via the endoscopic Mayo Score

Detailed Description

The proposed prospective tofacitinib registry is a prospective patient cohort with the goal of evaluating the efficacy and safety of this drug in "real life". All patients starting tofacitinib for ulcerative colitis in the setting of standard of care therapy will be eligible within of 4 weeks of start of therapy. Preferentially, patients will be enrolled at the visit where therapy is initiated. At baseline patient characteristics including extent of disease, previous therapies (including number of previously failed biologics) and pro-inflammatory laboratory markers (CRP, if available calprotectin) will be captured in a prospective web-based database. Additionally, each consented study participant will be enrolled in a web-based prospective patient powered registry (PPR) to evaluate patient report outcomes (PRO's) (such as validated measures for depression, social satisfaction, pain, fatigue) and safety events (e.g. hospitalizations; herpes zoster, complications requiring discontinuation of tofacitinib).

The following outcomes will be assessed: Response and remission as assessed by the Simple Clinical Colitis Activity Index (SCCAI) (primary endpoint), in addition secondary outcomes will include: the partial Mayo score, the 6-point subscore of the Mayo score, and the Manitoba index, need for steroids, need for surgery or hospitalization, need for dosing intensification or reduction of dosing as well as persistence of tofacitinib therapy. Endoscopy information will be collected if done as part of routine care, but the study will not have an endoscopic requirement. Sites will be encouraged to report a Mayo endoscopic score if done as part of routine care as a secondary endpoint. The outcomes will be determined in the setting of the standard of care visits, which normally are scheduled at the end of induction (approx. 6-12 weeks after the start of tofacitinib) and during maintenance therapy after 4-6 and 9-12 months and then every 3-4 months up to 36 months. PRO's and safety will be assessed with the PPR instrument at baseline, daily in the first 2 weeks to better understand rapidity of onset, and after 6,10,14,22,30,38,46 and 54 weeks and then every 3-4 months up to 36 months. The analyses of these data will facilitate UC patient care and improve the overall quality of IBD therapy in the US and worldwide. This study is to be conducted according to US and international standards of Good Clinical Practice (FDA Title 21 part 312 and International Conference on Harmonization guidelines), applicable government regulations and Institutional research policies and procedures.

Study Timeline

• Study Start: 2018-11-27
• Study First Submitted: 2018-12-04
• Study First Submitted QC: 2018-12-10
• Study First Posted: 2018-12-11
• Primary Completion: 2023-01-29
• Status Verified: 2024-01
• Study Completion: 2024-01-29
• Last Update Submitted: 2024-01-29
• Last Update Posted: 2024-01-31

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 103

Inclusion Criteria

1. Adult patients, age 18 years or older, with UC, who within 2 weeks have been started on tofacitinib therapy for moderate to severe UC or who plan to start this therapy within the next 2 weeks. The start of the tofacitinib therapy must have been or be initiated in the setting of standard of care therapy
2. Anticipation that the patient will be followed by the participating center at least for the next 12 months
3. Diagnosis of UC must be established on the basis of standard clinical, radiographic, endoscopic, and histologic criteria as described below.

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Exclusion Criteria

• 1. Patients will be excluded if they meet any of the following criteria:

  2. Inability to provide informed consent

  3. Patients presenting for a one-time consultation

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Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Change in clinical response from baseline	At baseline and at approximately 2, 4, 8, 20 and 52 weeks after start of tofacitinib	Clinical response as assessed by the Simple Clinical Colitis Activity Index (SCCAI)

Secondary Outcome Measures

Name	Time	Method
Change in clinical remission from baseline	At baseline and at approximately 2, 4, 8, 20 and 52	Clinical remission as assessed by the Simple Clinical Colitis Activity Index (SCCAI)
Persistence of the initial tofacitinib dose	12 months	Persistence of initial tofacitinib dose

Trial Locations

Locations (1)

Division of Gastroenterology and Hepatology; 🇺🇸 Chapel Hill, North Carolina, United States