Crohn's Disease (CD), Indeterminate Colitis, Inflammatory Bowel Disease (IBD), Ulcerative Colitis (UC)
Conditions
Keywords
Zymfentra, ZEST
Brief summary
The goal of this observational study is to learn about how effective Zymfentra (IFX=dyyb) is when treating patients with Crohn's disease (CD) and ulcerative colitis (UC) Does Zymfentra lead to a reduction in symptoms at intervals throughout one year? Participants being prescribed Zymfentra (IFX-dyyb as part of their regular medical care for CD or UC will answer online survey questions about their bowel habits for 1 year.
Interventions
None listed
Sponsors
University of North Carolina, Chapel Hill
Celltrion
Study design
Observational model
COHORT
Time perspective
PROSPECTIVE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
\- 1. Adult patients, age 18 years or older, with Crohn's disease (CD), ulcerative colitis (UC) or Inflammatory Bowel Disease Unclassified (IBDU), who are either starting Zymfentra at week 10 (IFX-dyyb) in the setting of standard-of-care initiation with intravenous Infliximab (IFX) originator or IFX biosimilars induction therapy at weeks 0,2,6 or switching from intravenous IFX originator or IFX biosimilars during maintenance therapy to Zymfentra (IFX-dyyb) 2. Anticipation that the patient will be followed by the participating center for the next 12 months. 3\. Diagnosis of CD, UC or IBDU must be established based on standard clinical, radiographic, endoscopic, and histologic criteria as described below. The following diagnostic criteria were developed by the NIDDK IBD Genetics Consortium and are provided as guidelines to complete documentation on individuals with CD, UC or IBDU: A) Symptoms including one or more: diarrhea, rectal bleeding, abdominal pain, fever, complicated perianal disease, extraintestinal manifestations, weight loss or failure to thrive. AND B) Symptoms on two or more occasions separated by at least 8 weeks or ongoing symptoms of at least 6 weeks duration. When there has been a single episode of colitis (in some instances less than 6 weeks duration) resulting in colectomy and resolution of disease symptoms, pathology on the colectomy specimen should be consistent with idiopathic IBD and microbiology studies should be negative. AND C) One or more of the following providing objective evidence of inflammation: Endoscopic: Mucosal edema, erythema, loss of normal submucosal vasculature, friability, ulceration, stricture formation, pseudopolyps, mucosal edema, erythema. Where there are only minor changes (mucosal edema, erythema, loss of normal submucosal vasculature, friability) mucosal biopsies should have been done to confirm the presence of IBD. Radiologic: Mucosal thickening and/or nodularity, ulceration, stricture, pseudopolyps, fistula formation, pseudosacculation. Minor changes alone (mucosal thickening and/or nodularity) should not be sufficient to make a diagnosis of IBD. Histologic: Mucosal erosion or ulceration, architectural changes of crypts, Paneth cell metaplasia (in colon), transmural inflammatory infiltrate\*, fibrosis of muscularis propria\*, noncaseating granuloma\*. \* CD Individuals with IBD should be classified into one of three categories, based on most recent diagnosis: Crohn's disease (CD): 1. Evidence of small intestinal inflammation with endoscopically, radiologically or histologically demonstrated ulcerations, fistulation, mucosal fissuring, nodularity or cobblestoning, stricture formation or histologically demonstrated transmural inflammation with or without granuloma formation. 2. Isolated esophageal, gastric or duodenal inflammation with the finding of noncaseating granuloma. 3. Colonic inflammation which is patchy (normal segments separating areas of inflammation, as described above) or associated with one or more of the following features: complete rectal sparing, multiple (\>10) aphthoid ulcers, deep ulceration (into the muscularis propria), transmural inflammation, extensive fibrosis and wall thickening, fistulation, non-caseating granuloma. (N.B. See note below regarding patchiness of endoscopically observed inflammation in patients with partially treated ulcerative colitis.) 4. The presence of complex suppurative perianal disease (i.e. more than a superficial fistula or uncomplicated superficial abscess). 5. If there are fewer than 10 aphthoid ulcers in the cecum (and the rest of the colon appears normal) in a patient with small bowel disease then this should be called small bowel disease only. Similarly, if the colon is normal except for the presence of a fistula extending from inflamed small bowel, the patient should be said to have small bowel disease alone. If the cecum is involved with ulcers larger than aphthoid ulcers or ulcers that are deep or if the involvement has resulted in deformity of the cecum this would be considered to be colonic involvement. Ulcerative Colitis (UC) 1\) Superficial inflammation and/or ulceration (involving only the mucosa and submucosa) of the colon which is continuous from the rectum extending proximally without skip lesions or complete rectal sparing (N.B. Relative rectal sparing is allowed for patients receiving topical rectal therapy; patchiness of endoscopic inflammation may be observed in patients with partially treated ulcerative colitis). 2\) In patients with proctitis or left-sided ulcerative colitis there may be an area of inflammation in the cecum, usually surrounding the appendiceal orifice. 3\) No inflammation of the small intestine ("backwash ileitis" is allowed - non-stricturing superficial inflammation of the terminal ileal mucosa associated with severe pancolitis which resolves following medical or surgical treatment of the colitis). 4\) No features of Crohn's disease listed above. Inflammatory Bowel Disease Unclassified (IBDU): 1. Confirmed IBD by A, B and C above. 2. Physician unable to classify individual into either CD or UC based on above criteria and/or patient has features of both CD and UC with none of the feature's diagnostic of one or the other.
Exclusion criteria
* 1\. Patients will be excluded if they meet any of the following criteria: 1. Inability to provide informed consent. 2. Non-English speaking 3. Patients presenting for a one-time consultation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical remission as evaluated by the Simple Clinical Colitis Activity Index (SCCAI) for the patient-reported outcomes. | Weeks 0,1, 2, 4, 6,10, 14, 18, 24, 36, and 52. | The SCCAI is a 6-item that describes the symptoms and disease activity of a patient with UC at the time of assessment. A score of 0-4 is considered a clinical range of remission (but with more refined definitions of clinical remission with SCCAI ≤2 and very mild symptoms with a score \>2 ≤4), 5-7 mild activity, 8-16 moderate activity and \> 16 severe activity. A response will be defined as a decrease of the SCCAI score \< 5 points in patients with a baseline SCCAI ≥5. |
| Clinical remission as evaluated by the Simple Crohn's Disease Activity Index (sCDAI for the patient-reported outcomes. | Weeks 0,1, 2, 4, 6,10, 14, 18, 24, 36, and 52 | The Short Crohn's Disease Activity Index (sCDAI) is a simplified version of the Crohn's Disease Activity Index (CDAI), used to assess disease severity in Crohn's disease patients. It reduces the number of variables required, making it easier and quicker to use in clinical practice. Recent data demonstrated, that collections of the parameters on a single day equally reflects reliable disease activity compared to a collection of data over 7 consecutive days, which is often hampered by missing data. A score of \< 150, 150-219, 220-450 and \>450 reflects remission, mild, moderate and severe Crohn's disease activity. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Response as measured by the Simple Endoscopic Score for Crohn's disease (SES-CD) | Through study completion, an average of 1 year | The Simple Endoscopic Score for Crohn's Disease (SES-CD) is a tool used to objectively measure the severity of Crohn's disease based on the extent and severity of ulcers, affected surface area, and luminal narrowing during an endoscopy. The total score is the sum of scores for these four features, and it is categorized as follows: 0-2 for remission, 3-6 for mild activity, 7-15 for moderate activity, and greater than 15 for severe activity. Mucosal healing will be defined by an SES-CD \< 4 |
| Response as measured by the endoscopic Mayo score for ulcerative colitis | Through study completion, an average of 1 year | The Mayo endoscopic score is a four-point scale (1 to 3) used to assess the severity of ulcerative colitis (UC) based on a colonoscopy. It evaluates the severity of inflammation through findings like erythema, vascular pattern, friability, erosions, and spontaneous bleeding, with higher scores indicating more severe disease. Mucosal healing will be defined by an endoscopic Mayo score \<1. |
| Mucosal healing will be assessed in the setting of standard-of-care calprotectin levels. | Weeks 0, 14, 24, and 52. | Calprotectin is a surrogate marker of intestinal inflammation, and levels ≥ 250 mcg/g stool are associated with active mucosal inflammation, whereas levels \<150 mcg are considered to represent mild or no mucosal inflammation |
| Response as measured by Patient-Reported Outcomes Measurement Information System (PROMIS)- Depression | Weeks 0, 24, and 52. | PROMIS measure of depression measures well-being. This is calculated as T scores. A clinically meaningful difference is considered to be a change in T score of ≥ 2.5 (scores are normalized at 50 with a standard deviation of 10). Higher scores mean more severe depression. Differences in PROMIS scores compared to baseline will be assessed. |
| Response as measured by Patient-Reported Outcomes Measurement Information System (PROMIS) -Anxiety Score | Weeks 0, 24, and 52. | PROMIS measure of anxiety measures well-being. This is calculated as T scores. A clinically meaningful difference is considered to be a change in T score of ≥ 2.5 (scores are normalized at 50 with a standard deviation of 10). Higher scores indicate greater anxiety severity Differences in PROMIS scores compared to baseline will be assessed. |
| Response as measured by Patient-Reported Outcomes Measurement Information System (PROMIS) -Social Satisfaction Score | Weeks 0, 24, and 52. | PROMIS measure of satisfaction measures well-being. This is calculated as T scores. A clinically meaningful difference is considered to be a change in T score of ≥ 2.5 (scores are normalized at 50 with a standard deviation of 10). Higher scores indicate greater satisfaction. Differences in PROMIS scores compared to baseline will be assessed. |
| Response as measured by Likert scale urgency Score | Weeks 0,1, 2, 4, 6,10, 14, 18, 24, 36, and 52 | Urgency will be measured by the 11-point Likert scale urgency question. Score range is 0-10. The higher the score, the worse the urgency. |
| Response as measured by Functional Assessment of Chronic Illness Therapy (FACIT)- Fatigue Scale Score | Weeks 0, 24, and 52 | Fatigue will be determined by the validated FACIT-F questionnaire. The FACIT-F is a 13-item measure that assesses self-reported fatigue and its impact upon daily activities and function. Score range is 0-52. The higher the score, the better the quality of life. |
| Response as measured by The Short Inflammatory Bowel Disease Questionnaire (SIBDQ) score | Weeks 0,4,10,14,18,24,36 and 52. | The SIBDQ is a disease-specific health-related quality of life (HRQOL) questionnaire, able to detect and define meaningful clinical changes in inflammatory bowel disease (IBD) participants by measuring physical, social and emotional status. The SIBDQ consists of 10 questions; each question is scored on a scale from 1 (poor QOL) to 7 (optimum QOL). A higher score indicates a better health-related quality of life. Total scores range from 10 (poor QoL) to 70 (good QoL). |
| Response as measured by The Work Productivity and Activity Impairment questionnaire (WPAI) | Weeks 0, 24, and 52 | The WPAI was designed to measure absenteeism, presenteeism and activity impairment attributable to ill-health over the preceding 7 days. The WPAI calculates percentage impairment (maximum 100%) with higher numbers representing greater work impairment. |
Countries
United States
Contacts
CONTACTSusan Jackson
PRINCIPAL_INVESTIGATORHans Herfarth, MD, PhD
University of North Carolina
Outcome results
None listed