Investigation of the Faecal Loss of Vedolizumab and Its Role in Influencing Serum Drug Levels, Outcomes and Response in Ulcerative Colitis

Investigation of the Faecal Loss of Vedolizumab and Its Role in Influencing Serum Drug Levels, Outcomes and Response in Ulcerative Colitis

The purpose of this study is to study the loss of vedolizumab in stool in patients with active ulcerative colitis (UC).

Patients with moderate-to-severe UC who are commencing induction therapy with vedolizumab will be enrolled into a prospective study and stool will be collected for faecal vedolizumab measurement at days 1, 4 and 7; and again at weeks 2, 6 and 14. They will also be evaluated at three time-points (weeks 2, 6 and 14) for clinical and biochemical UC disease activity as well as serum vedolizumab concentrations and anti-vedolizumab antibodies.

Primary objective

- To determine whether vedolizumab is present in significant quantities in the stool of patients receiving induction therapy with vedolizumab for active UC.

Secondary objective (s)

• To evaluate whether the presence and quantity of vedolizumab in stool can be used to predict primary non-response to vedolizumab.
• To explore whether a correlation exists between stool vedolizumab concentrations, serum vedolizumab concentrations and UC disease activity and extent.
• To determine whether there is a correlation between stool and serum vedolizumab levels and trafficking of Th1/Th17 effector memory CD4+ T-cells (the key pathogenic subset in IBD) to the colon in UC.

Inclusion Criteria:

• Aged 18 years or over, either male or female

• Moderate-to-severe UC, defined as:

  - SCCAI > 5 and, i. A raised fecal calprotectin (> 59 μg/g) or, ii. A raised CRP (> 5 mg/L) or, iii. Endoscopic disease activity Mayo 2 or above, Evaluated within 6 weeks of study enrollment

• Commencing vedolizumab treatment

• Sufficient English language skills to understand the patient information sheet and consent form

Exclusion Criteria:

• Contra-indication to vedolizumab (i.e. known serious or severe hypersensitivity reaction to vedolizumab or any of its excipients)
• Imminent need for colectomy (i.e. colectomy is being planned)
• Previous ileoanal pouch formation
• Active severe infections such as tuberculosis, sepsis, cytomegalovirus, listeriosis, and opportunistic infections