Clinical Trial Summary
The study is to determine whether active surgical intervention promotes disease remission in
patients with Crohn's Disease (CD).The management of CD involves both maintenance medication
and medication used to control flares of the disease. The goal of maintenance therapy in CD
is to maintain steroid- free remission, clinically and endoscopically. This requires regular
clinical assessment including history, physical examination and at times colonoscopic
examination. Other tools of assessment include blood (e.g. CRP, WCC) and stool (calprotectin)
testing for inflammatory markers and imaging including MRI, CT or ultrasound.
The choice of maintenance treatment in CD is determined by disease extent, disease course
(frequency of flares), failure of previous maintenance treatment, severity of the most recent
flare, treatment used for inducing remission during the most recent flare, safety of
maintenance treatment, and cancer prevention. The mainstay of maintenance medication are the
5-aminosalicylic acid compounds (5-ASA) such as mesalazine or sulphasalazine.
These compounds are commonly taken orally in formulations that predominantly deliver the
active 5-ASA component to the colon. Alternatively, or in addition, mesalazine preparations
can be delivered topically via enema or suppository if the disease only involves the left
side of the colon (although it is only PBS funded for topical therapy during a flare and not
for maintenance of remission - even though it also works in this setting). The majority of
patients can be managed with maintenance 5-ASA compounds most of the time. For patients who
have repeated flares of disease on 5-ASA maintenance therapy (1 or more flares in a year
needing steroids), thiopurine medication such as azathioprine or 6-mercapropurine should be
used. These medications induce systemic immunosuppression, reduce the incidence and severity
of flares of colitis but also slightly increase the risk of some infections and malignancy.
Anti TNF agents such as infliximab or adalimumab have been shown to have benefit in
maintaining remission in CD (and are licensed for this indication by the TGA), however these
agents are very expensive and not funded by the pharmaceutical benefits scheme in Australia
and so, are not readily available. The anti TNF agents also give an increased risk of
infection, particularly latent TB reactivation.
Mild flares of CD can be managed with higher doses of oral 5-ASA compounds or the addition of
topical 5-ASAs given via enema or suppository. More severe flares are usually managed with a
course of systemic corticosteroid. These can be given intravenously in acute, severe disease
or orally in less severe flares. The steroids should then be tapered over time and
discontinued. There is no indication for long term steroid use in CD and prolonged steroid
use is associated with a number of complications including infection, osteoporosis, obesity,
diabetes, poor wound healing, thinning skin, mood changes and insomnia. Severe flares of CD
not responsive to steroids may respond to rescue therapy with the addition of either
cyclosporin or anti-TNF therapy.
Patients in whom colonic inflammation cannot be controlled adequately frequently undergo
total colectomy. This may be done electively (for refractory disease) or emergently in acute
fulminant colitis. Colectomy entails surgical risk that is higher in the emergent setting;
this risk includes infection, wound breakdown and a mortality rate. Colectomy is considered
"curative" for CD especially if they have an ileostomy stoma created, however, it frequently
also leads to complications both short- and long-term. In addition, in patients in whom an
ileal-anal pouch is fashioned up to 50% will subsequently develop pouchitis at 4 years post
surgery.
Patient eligibility was determined during a 5-week screening period, during which time
details on patient demographics, medical history, and previous and concomitant medications
were obtained,and the following assessments were completed: viral serology, stool culture,
Crohn's Disease Activity Index (CDAI) patient diary and clinical score, Simple Endoscopic
Score for Crohn's Disease (SES-CD), colonoscopy and colonic biopsy, stool collection for
faecal biomarkers, vital signs, and laboratory evaluations.
All participants need to be subjected to rigorous assessments mentioned above at week 4, week
8 and week 12 after receiving active surgical intervention (two kinds: one is colostomy, and
the other one is colonic exclusion).
