Regulation of Mucosal Healing in Inflammatory Bowel Disease

The objective of the current study is to compare non-healing colonic ulcers in patients with inflammatory bowel disease (IBD) with iatrogenic colonic ulcers (biopsy sites) in healthy control patients and patients with rheumatoid or psoriatic arthritis. Patients will be biopsied at baseline and again at a follow-up visit in a "biopsy of the biopsy" approach. These biopsies will be used to reveal patterns about gene expression and mitochondrial function during ulcer healing.

Induction of mucosal healing in inflammatory bowel disease (IBD) is associated with reduced hospitalizations, surgeries, and reduced cancer risk. However, previous studies have shown that 54-69% of ulcerative colitis (UC) patients fail to heal ulcers after several weeks of treatment, and roughly half do not maintain remission at one year. The single most important factor in preventing severe medical consequences, like colon removal surgery or cancer, is treatment to completely heal the top layer of the intestine as quickly as possible. Healing is a complex process and the dysfunction observed in colitis can only be fully understood by comparison to healing in non-IBD patients. This is a prospective trial involving three groups of patients: 1) IBD patients with active disease, newly treated with anti-TNF therapy (biologic failure or naïve); 2) non-IBD patients with rheumatoid/psoriatic arthritis who are receiving anti-TNF therapy, and 3) healthy control patients. Biopsies will be collected at baseline during standard of care endoscopy and at a follow-up research endoscopy. This study will probe mechanisms of ulcer healing by analyzing gene expression patterns and mitochondrial function.

mucosal, rheumatoid arthritis, psoriatic arthritis, ulcer, colitis, Crohn's, mitochondria, biopsy, wound, biologic, anti-TNF

Participants in this group will have been diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) and have either failed treatment with biologics or be naive to biologic therapy.

Participants in this group will have been diagnosed with rheumatoid (RA) or psoriatic arthritis (PsA) and will be receiving anti-TNF antibody therapy at the time of enrollment.

During the initial colonoscopy, 16-20 biopsies will be collected in addition to standard of care biopsies, and biopsy sites will be tattoed. Patients will return for a follow-up colonoscopy 4-35 days later. An additional 16-20 biopsies will be collected in a "biopsy of the biopsy" approach.

Mitochondrial DNA copy number will be measured in epithelial cells collected from biopsies taken during the initial colonoscopy and at the follow-up colonoscopy.

Relative expression of cMyc (mRNA) will be measured in epithelial cells collected from biopsies taken during the initial colonoscopy and at the follow-up colonoscopy.

Relative expression of PGC-1 alpha (mRNA) will be measured in epithelial cells collected from biopsies taken during the initial colonoscopy and at the follow-up colonoscopy.

Relative expression of Ki67 alpha (mRNA) will be measured in epithelial cells collected from biopsies taken during the initial colonoscopy and at the follow-up colonoscopy.

The number of visible ulcers will be assessed during the follow-up endoscopy for healthy patients and rheumatoid/psoriatic arthritis patients only.

The Mayo Endoscopic Score will be calculated at baseline and at follow-up in patients with ulcerative colitis only. The Mayo Endoscopic score is evaluated for the macroscopically most severely inflamed segment: 0 for normal or inactive disease; 1 for erythema, decreased vascular pattern, mild friability; 2 for marked erythema, absent vascular pattern, friability, erosions; 3 ulcerations or spontaneous bleeding. Segmental scores range from 0-3; higher scores indicate more severe disease.

The Simple Endoscopic Score (SES) will be calculated at baseline and follow-up in patients with Crohn's disease (CD) only. The SES-CD score incorporates ulcer size, narrowing, and the area affected by disease or ulceration. Scores range from 0-12; lower scores indicate remission while higher scores indicate severe endoscopic activity.

Levels of fecal calprotectin (ug/g) will be measured from stool samples collected from patients at any time during the study protocol.

Inclusion Criteria (Group 1): Diagnosed ulcerative colitis or Crohn's disease Biologic failure or naive to biologic treatment Eligible to be treated with anti-TNF therapy Inclusion Criteria (Group 2): Diagnosed rheumatoid or psoriatic arthritis Receiving anti-TNF antibody therapy at the time of enrollment Inclusion Criteria (Group 3): Endoscopically unremarkable colonic mucosa Absence of inflammatory bowel disease Exclusion Criteria: Classified in an anesthesia risk group, ASA Class =4 History of bleeding diathesis or coagulopathy Stroke or transient neurological attack with the last 6 months Pregnant Receiving anticoagulants or anti-platelet medications other than low-dose aspirin Receiving steroid therapy or metformin HIV positive Incarceration History of total proctocolectomy History of system chemotherapy within 18 months Uncontrolled intercurrent illness