Zymfentra (Infliximab-dyyb) REal World Cohort STudy

Overview

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.

Primary outcome measures

• Clinical remission as evaluated by the Simple Clinical Colitis Activity Index (SCCAI) for the patient-reported outcomes. [Time frame: Weeks 0,1, 2, 4, 6,10, 14, 18, 24, 36, and 52.]
• Clinical remission as evaluated by the Simple Crohn's Disease Activity Index (sCDAI for the patient-reported outcomes. [Time frame: Weeks 0,1, 2, 4, 6,10, 14, 18, 24, 36, and 52]

Secondary outcome measures (10)

• Response as measured by the Simple Endoscopic Score for Crohn's disease (SES-CD) [Time frame: Through study completion, an average of 1 year]
• Response as measured by the endoscopic Mayo score for ulcerative colitis [Time frame: Through study completion, an average of 1 year]
• Mucosal healing will be assessed in the setting of standard-of-care calprotectin levels. [Time frame: Weeks 0, 14, 24, and 52.]
• Response as measured by Patient-Reported Outcomes Measurement Information System (PROMIS)- Depression [Time frame: Weeks 0, 24, and 52.]
• Response as measured by Patient-Reported Outcomes Measurement Information System (PROMIS) -Anxiety Score [Time frame: Weeks 0, 24, and 52.]
• Response as measured by Patient-Reported Outcomes Measurement Information System (PROMIS) -Social Satisfaction Score [Time frame: Weeks 0, 24, and 52.]
• Response as measured by Likert scale urgency Score [Time frame: Weeks 0,1, 2, 4, 6,10, 14, 18, 24, 36, and 52]
• Response as measured by Functional Assessment of Chronic Illness Therapy (FACIT)- Fatigue Scale Score [Time frame: Weeks 0, 24, and 52]
• Response as measured by The Short Inflammatory Bowel Disease Questionnaire (SIBDQ) score [Time frame: Weeks 0,4,10,14,18,24,36 and 52.]
• Response as measured by The Work Productivity and Activity Impairment questionnaire (WPAI) [Time frame: Weeks 0, 24, and 52]

Eligibility criteria

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):

• 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.
• Isolated esophageal, gastric or duodenal inflammation with the finding of noncaseating granuloma.
• 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.)
• The presence of complex suppurative perianal disease (i.e. more than a superficial fistula or uncomplicated superficial abscess).
• 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):

• Confirmed IBD by A, B and C above.
• 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:

• Inability to provide informed consent.
• Non-English speaking
• Patients presenting for a one-time consultation.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Observational model

Cohort

Study locations

United States · 11 centers

• Yale University School of Medicine — New Haven
• University of Miami — Miami
• AdventHealth — Orlando
• University of Iowa — Iowa City
• Mercy Medical Center — Baltimore
• Brigham and Women's Hospital — Boston
• New York University — New York
• University of North Carolina — Chapel Hill
• … and 3 more centers

Publications

• Popmihajlov Z, Pang L, Brown E, Joshi A, Su SC, Kaplan SS, Willis ED. A post hoc analysis utilizing the FDA toxicity grading scale to assess injection site adverse events following immunization with the live attenuated Zoster Vaccine (ZVL). Hum Vaccin Immunother. 2018;14(12):2916-2920. doi: 10.1080/21645515.2018.1502517. Epub 2018 Sep 5. PMID 30024827
• Youssef M, Hossein-Javaheri N, Hoxha T, Mallouk C, Tandon P. Work Productivity Impairment in Persons with Inflammatory Bowel Diseases: A Systematic Review and Meta-analysis. J Crohns Colitis. 2024 Sep 3;18(9):1486-1504. doi: 10.1093/ecco-jcc/jjae057. PMID 38647194
• Dubinsky MC, Panaccione R, Lewis JD, Sands BE, Hibi T, Lee SD, Naegeli AN, Shan M, Green LA, Morris N, Arora V, Bleakman AP, Belin R, Travis S. Impact of Bowel Urgency on Quality of Life and Clinical Outcomes in Patients With Ulcerative Colitis. Crohns Colitis 360. 2022 Jun 3;4(3):otac016. doi: 10.1093/crocol/otac016. eCollection 2022 Jul. PMID 36777426
• Singh S, Ananthakrishnan AN, Nguyen NH, Cohen BL, Velayos FS, Weiss JM, Sultan S, Siddique SM, Adler J, Chachu KA; AGA Clinical Guidelines Committee. Electronic address: clinicalpractice@gastro.org. AGA Clinical Practice Guideline on the Role of Biomarkers for the Management of Ulcerative Colitis. Gastroenterology. 2023 Mar;164(3):344-372. doi: 10.1053/j.gastro.2022.12.007. PMID 36822736
• Higgins PD, Schwartz M, Mapili J, Krokos I, Leung J, Zimmermann EM. Patient defined dichotomous end points for remission and clinical improvement in ulcerative colitis. Gut. 2005 Jun;54(6):782-8. doi: 10.1136/gut.2004.056358. PMID 15888785
• Peyrin-Biroulet L, Panes J, Sandborn WJ, Vermeire S, Danese S, Feagan BG, Colombel JF, Hanauer SB, Rycroft B. Defining Disease Severity in Inflammatory Bowel Diseases: Current and Future Directions. Clin Gastroenterol Hepatol. 2016 Mar;14(3):348-354.e17. doi: 10.1016/j.cgh.2015.06.001. Epub 2015 Jun 11. PMID 26071941
• Thia K, Faubion WA Jr, Loftus EV Jr, Persson T, Persson A, Sandborn WJ. Short CDAI: development and validation of a shortened and simplified Crohn's disease activity index. Inflamm Bowel Dis. 2011 Jan;17(1):105-11. doi: 10.1002/ibd.21400. PMID 20629100
• Barnes EL, Hanson JS, Regueiro MD, Saha S, Sands BE, Rubin DT, Dubinsky MC, Siegel CA, Gazis DR, Crawford JM, Long MD. Older Adult Patients Use More Aminosalicylate Monotherapy Compared With Younger Patients With Inflammatory Bowel Disease: TARGET-IBD. J Clin Gastroenterol. 2022 Jul 1;56(6):529-535. doi: 10.1097/MCG.0000000000001557. Epub 2021 Jun 11. PMID 34115661

Identifiers

NCT: NCT07237516 · 25-2184

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗