Real-world Effectiveness of Ustekinumab in Participants Suffering From Inflammatory Bowel Disease (Crohn's Disease or Ulcerative Colitis) With Extra-intestinal Manifestations or Immune-mediated Inflammatory Diseases (TENOR)

Effectiveness of Ustekinumab in Patients Suffering From Inflammatory Bowel Disease (Crohn's Disease or Ulcerative Colitis) With Extra-intestinal Manifestations or Immune-mediated Inflammatory Diseases in a Real-world Setting

The purpose of this study is to assess the effectiveness of ustekinumab on extra-intestinal manifestations (EIMs) and immune-mediated inflammatory diseases (IMIDs) associated with inflammatory bowel disease (IBD) (both Crohn's Disease [CD] and Ulcerative Colitis [UC]).

Study Overview

• Status: Completed
• Conditions: Crohn Disease; Colitis, Ulcerative
• Intervention / Treatment: Drug: Ustekinumab

• Study Type: Observational
• Enrollment (Actual): 111

Contacts and Locations

Study Locations

• France
  • Vandoeuvre les Nancy, France, 54511
    • CHU de Nancy - Hopital de Brabois

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

The study population will be participants with a confirmed diagnosis of moderate to severe Crohn's Disease (CD) or Ulcerative Colitis (UC) with at least one extra-intestinal manifestation (EIM) or immune-mediated inflammatory disease (IMID) of interest and for which a treatment with ustekinumab is indicated according to the clinical practice and Summary of Product Characteristics (SmPC).

Description

Inclusion Criteria:

• With a confirmed diagnosis of CD or UC
• With at least one EIM of interest (cutaneous: pyoderma gangrenosum; erythema nodosum, articular: axial spondyloarthritis and peripheral spondyloarthritis with and without psoriasis, dactylitis, enthesitis; ocular: uveitis) and/or at least one IMIDs of interest (cutaneous: psoriasis, atopic dermatitis, hidradenitis suppurativa), suspected or confirmed, that is active at the time of screening
• Starting ustekinumab as a biologic therapy for CD or UC treatment independently of their enrollment into the study
• Using ustekinumab according to the SmPC
• Only for participants with CD: has had an inadequate response with or lost response to or be intolerant to conventional therapy including azathioprine, 6-mercaptopurine or corticosteroids or; at least one tumor necrosis factor (TNF) blocker (adalimumab, infliximab). Only for participants with UC: Have had an inadequate response with, lost response to, or were intolerant to either conventional including azathioprine, 6-mercaptopurine or corticosteroids or a biologic

Exclusion Criteria:

• Participants suffering from a psoriasis induced by a biological therapy at inclusion (including TNF blocker) or participant presenting an active psoriasis that was diagnosed before the time of inflammatory bowel disease (IBD) diagnosis
• Participants currently enrolled in an investigational study (or have been in the past 2 months) or are unwilling or not able to understand or provide their consent

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort

Intervention / Treatment

Inflammatory Bowel Disease (IBD) Participants with EIMs and/or IMIDs; IBD (Crohn's Disease [CD] or Ulcerative Colitis [UC]) participants with suspected extra-intestinal manifestations (EIMs) and/or one or more immune-mediated inflammatory diseases (IMIDs) will be enrolled into the study to assess effectiveness of ustekinumab on EIMs and/or IMIDs associated with IBD (both CD and UC). Participants will receive ustekinumab at study entry (Week 0) as treatment for IBD according to standard clinical practice and will be followed up to 24 weeks (+/- 3 weeks). Only data available per clinical practice will be collected within this study.

Drug: Ustekinumab; No study treatment will be administered as a part of this study. Participants who are initiating the treatment with ustekinumab, will be observed according to standard clinical practice.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants Achieving a Clinical Response (CR) on at Least one Extra-intestinal Manifestation/Immune-mediated Inflammatory Disease (EIM/IMID) Associated with Inflammatory Bowel Disease (IBD) at Week 24	CR will be determined based on the measures collected by the investigators which will be assessed by the specialists based on these parameters: 2 points reduction in physician global assessment (PGA) score or PGA 0 or 1 (0= clear to 5=very severe) achieved for cutaneous disease, or resolution of lesions for Erythema nodosum (dermatology); decrease of 50 percent (%) of ankylosing spondylitis disease activity index (BASDAI) (1=no problem to 10=worst problem) for axial spondyloarthritis (SpA); disease activity score (DAS)28 (derived from 4 items with score <2.6 [disease remission] and >5.1 [severe disease activity]) of moderate and good response achieved in peripheral SpA plus 2 points reduction in PGA score or PGA 0 or 1 achieved in case of associated psoriasis; resolution of dactylitis, decrease of 50% of Leeds enthesitis index [LEI-6] score which ranges from 0 [pain/tenderness absent] to1 [pain/tenderness present] for enthesitis, (rheumatology); resolution of uveitis (ophthalmology).	Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants with Change from Baseline in Clinical Response for Crohn's Disease (CD) as Measured by Harvey-Bradshaw Index (HBI)	HBI is defined as total HBI score of 4 points or less. HBI score consists of clinical parameters of general well-being (0 to 4), abdominal pain (0 to 3), number of liquid stools per day, abdominal mass (0 to 3), and complications (8 items, score 1 per item) lower scores indicating better well-being.	Baseline, Week 16 and Week 24
Percentage of Participants Achieving Remission for CD as Measured by HBI	Percentage of participants achieving remission for CD will be measured using the HBI Score less than or equal to (<= 4). HBI remission is defined as total HBI score of 4 points or less. HBI score consists of clinical parameters of general well-being (0 to 4), abdominal pain (0 to 3), number of liquid stools per day, abdominal mass (0 to 3), and complications (8 items, score 1 per item) lower scores indicating better well-being.	Up to Week 24
Change from Baseline in Partial Mayo Score	Mayo scoring system is used for assessment of ulcerative colitis activity. The Mayo score consists of 4 subscores (stool frequency, rectal bleeding, physician's global assessment, and endoscopy findings) each ranging from 0 to 3. Partial Mayo score is calculated as the sum of 3 subscores (stool frequency, rectal bleeding, and physician's global assessment) and ranges from 0 to 9 points. Higher score indicates severe disease. Change from baseline in the Partial Mayo Score of at least 3 points and at least 30 percent, with an accompanying decrease in the subscore for rectal bleeding of at least 1 point or an absolute subscore for rectal bleeding of 0 or 1 will be reported.	Baseline, Week 16 and Week 24
Percentage of Participants Achieving Remission for UC as Measured by Partial Mayo Score (Score of <=2)	Percentage of participants achieving remission for UC will be measured using the Partial Mayo score Score less than or equal to <=2). Partial Mayo score is calculated as the sum of 3 subscores (stool frequency, rectal bleeding, and physician's global assessment) and ranges from 0 to 9 points. Higher score indicates severe disease.	Up to Week 24
Change from Baseline in the Presence of Extra Intestinal Manifestations (EIMS) or Immune-Mediated Inflammatory Diseases (IMIDs)	Change from baseline in the presence of Extra Intestinal Manifestations (EIMs)/ Immune-Mediated Inflammatory Diseases (IMIDs) for its severity/activity will be determined.	Baseline and Week 24
Work Productivity and Activity Impairment (WPAI) Questionnaire	The WPAI is a validated, self-administered questionnaire that assesses work and activity impairment during the past 7 days due to IBD. The WPAI score ranges from 0 to10. Score 0 means IBD had no effect on work and score 10 indicates because of IBD, could not work at all.	Baseline, Weeks 16 and Week 24
Short Inflammatory Bowel Disease Questionnaire Score (Short IBDQ)	Short IBDQ is a health-related quality of life tool (HRQoL) to assess quality of life in adult participants with inflammatory bowel disease (IBD) having only 10 items with 4 domains: digestive symptoms (3 items), systemic symptoms (2 items), emotional disturbance (3 items), and social function (2 items). Participants are asked to recall symptoms and quality of life from the last 2 weeks and rate each item on a 7-point Likert scale (1=all of the time; 2=most of the time; 3=a good bit of the time; 4=some of the time; 5=a little bit of the time; 6=hardly any of the time; 7=none of the time). Total score is calculated by adding the scores from each domain; the total score ranges from 10 to 70, where minimum score =10 (poor HRQoL) and maximum score =70 (good HRQoL).	Baseline, Weeks 16 and 24
Functional Assessment of Chronic Illness Therapy Scale (FACIT)	FACIT-F scale is a 13 item fatigue scale with a 7 day recall period. It measures the level of fatigue during the usual daily activities. The level of fatigue is measured on a 4 point Likert scale (0=very much fatigued to 4=not at all fatigued). Total FACIT score is the sum of 13 items, ranging from 0 (not at all) to 52 (very much). Higher scores represent better outcomes.	Baseline, Weeks 16 and 24
Inflammatory Bowel Disease-Disability Index (IBD-DI)	The IBD-DI consists of 28 items that evaluate the 5 domains of overall health, body function, body structures, activity participation and environmental factors. Each item response is graded from 0 to 4 for each area evaluated (0 = very good; 1 = Good; 2 = medium; 3 = Bad; 4 = Very bad). The final composite score representative of the overall degree of disability ranging from -80 (maximum degree of disability) to 22 (no disability).	Baseline, Weeks 16 and 24
Number of Participants with Adverse Events	An adverse event is any untoward medical event that occurs in a participant administered an investigational product, and it does not necessarily indicate only events with clear causal relationship with the relevant investigational product.	Up to 37 weeks
Number of IBD Related Medical Visits	Number of IBD related medical visits as a part of medical resources utilization will be reported.	Week 24
Number of Days of IBD Related Hospitalization with Surgery	Number of days of IBD related hospitalization with surgery (defined as number of days from the day of admission to discharge) as a part of medical resources utilization will be reported.	Week 24
Number of Days of IBD Related Hospitalization Without Surgery	Number of days of IBD related hospitalization without surgery (defined as number of days from the day of admission to discharge) as a part of medical resources utilization will be reported.	Week 24
Number of IBD Related Emergency Visits	Number of IBD related emergency visits as a part of medical resources utilization will be reported.	Week 24

Collaborators and Investigators

• Sponsor: Janssen Cilag S.A.S.
• Investigators: Study Director: Janssen Cilag S.A.S., France Clinical Trial, Janssen Cilag S.A.S.

Study record dates

Study Major Dates

• Study Start (Actual): September 26, 2018
• Primary Completion (Actual): March 17, 2023
• Study Completion (Actual): March 17, 2023

Study Registration Dates

• First Submitted: July 20, 2018
• First Submitted That Met QC Criteria: July 20, 2018
• First Posted (Actual): July 31, 2018

Study Record Updates

• Last Update Posted (Actual): October 12, 2023
• Last Update Submitted That Met QC Criteria: October 11, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Ulcer; Inflammatory Bowel Diseases; Crohn Disease; Colitis; Colitis, Ulcerative; Dermatologic Agents; Ustekinumab
• Other Study ID Numbers: CR108498; CNTO1275CRD4012 (Other Identifier: Janssen Cilag S.A.S., France)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No