EUS Evaluation of Perianal and Peri-rectal Fistulizing Crohn's Disease With CERTOLIZUMAB Treatment

Peri-anal ( located around the anus, the opening of the rectum to the outside of the body)
fistulae are a major complication of Crohn's disease and occur in almost 30% of patients.
Patients with perianal fistulae suffer from severe pain, perianal drainage, and have
significant impairment of quality of life. Initial studies of Infliximab and Adalimumab in
patients with CD have shown perianal fistula healing with these medications. Infliximab and
Adalimumab are medications which reduce the effects of a substance in the body that can
cause inflammation. They are also used to treat Crohn's disease after other drugs have been
tried without successful treatment of symptoms. Although no studies have specifically
evaluated Certolizumab (Cimzia) treatment in fistulizing Crohn's disease, there is evidence
to its efficacy. Certolizumab reduces the effects of a substance in the body that can cause
inflammation. Certolizumab is used to treat the symptoms of Crohn's disease after other
drugs have been tried without successful treatment of symptoms. Studies with a small number
of patients who use Cimzia did not show any significant effect on fistula closure. However,
in a larger subgroup of patients with fistulae in PRECiSE 2 43.3% of those who received 3
induction injections of certolizumab followed by placebo, and 53.6% of those on certolizumab
400mg continuous treatment had fistula closure defined as no drainage on gentle compression
of at least 50% of open fistulae at any 2 consecutive visits, at least 3 weeks apart.
Perianal disease activity is usually monitored clinically. In clinical studies, two
evaluation methods have been used in attempts to unify the definition of perianal disease
activity. One method is the perianal Crohn's disease activity index (PDAI) which involves
questions regarding discharge, pain/ restriction of activities, restriction of sexual
activity, type of perianal disease, degree of induration (with scores >/=5 indicating active
disease, with decrease in PDAI of 2 or more points indicates improvement, and consider 0 as
healed. PDAI scale (Pouchitis Disease Activity Index). This scale analyzes and summarizes
different criteria: clinical, endoscopic and histological. Among clinical symptoms, an
important factor is the number of stools exceeding the post-operative average, bleeding,
re-occuring stomachaches, as well as body temperature above 37.8°C or 100°F. "Pouchitis" is
a term to describe inflammatory changes in the pouch created from the lower part of the
ileum. The patients suffer from high body temperature, stomachaches and watery stools with
small amounts of mucus, blood and soiling. An exam based technique, used in the Precise
trials is the Fistula Drainage Assessment indicating improvement or remission with closure
of individual fistulae defined as no fistula drainage despite gentle finger compression,
improvement defined as a decrease from baseline in the number of open draining fistulae of
greater than or equal to 50 percent for at least 2 consecutive visits (i.e. at least 4
weeks), and remission defined as closure of all fistulae that were draining at baseline for
at least 2 consecutive visits (i.e., at least 4 weeks). However both have not been
validated, and the response levels are usually evaluated several months into treatment. If
another method could provide early assessment / predictors of healing, it could make the
decision for the treatment of the gastroenterologist as well as the patient, easier to
determine if they should continue the biologic or stop. Studies have evaluated the use of
endoscopic ultrasound (EUS) to follow fistula assessment and healing, but none have
specifically assessed this in response to certolizumab treatment. EUS is increasingly used
and has been found to be equally accurate in the evaluation of perianal fistulae compared to
MRI of the pelvis. An accurate assessment and classification of fistulae can facilitate
further management including surgical planning, further medical treatment, or a combination
of both. EUS can evaluate for fistulae as well as abscesses and the relation to the anatomic
landmarks of the rectum including the sphincter muscles as well as adjacent organs such as
vagina and the bladder. EUS has the advantage of being more convenient for the patient than
an MRI. An MRI can take a long duration, can cause anxiety in those that are claustrophobic,
and is expensive. EUS is usually performed with sedation and by the treating physician
allowing a more personal evaluation of the fistula anatomy and correlation of endoscopic
mucosal findings. Thus, we propose to evaluate the use of certolizumab in Crohn's disease
patients with peri-anal and peri-rectal fistulae (an abnormal passage that leads from an
abscess or hollow organ or part to the body surface or from one hollow organ or part to
another) and to assess their response and healing (A perirectal abscess is a collection of
pus in the deep tissues surrounding the anus. Perirectal and perianal abscesses are thought
to develop from the glands surrounding the anus) based on EUS findings. This study can help
provide recommendations on fistula classification of EUS and use this classification to
provide EUS - based early predictors of response of treatment with certolizumab.

Inclusion Criteria:

- Conventional therapy here indicates non-biologic therapy. Study subjects would have
failed conventional and standard regimens of treatment such as immunomodulators
(azathioprine, 6-mercaptopurine, methotrexate) or mesalamines or corticosteroids.
Certolizumab is actually an approved regimen of treatment for Crohn's disease as
patients with perianal fistulas fall under those with moderately to severely active
disease. It is not an off-label indication, therefore would not require an IND. The
study goal is to look at EUS as a tool to determine how fistula healing occurs with
the use of certolizumab which is one of the biologic therapies used to treat
fistulizing Crohn's disease. Crohn's disease patients with peri-anal or peri-rectal
fistulizing disease. Moderate to severe Crohn's disease patients between the ages of
18 and 70 years with active peri-anal or peri-rectal fistula.

Exclusion Criteria:

- Pre-existing fistula improving on current medical therapy. Contraindication to
certolizumab use. Prior use of anti-TNF-alpha.