Ulcerative colitis (UC) is a chronic, progressive immunologically mediated disease
affecting nearly 1 million Americans. Up to one third of patients with UC will require
hospitalization for severe disease (termed 'acute severe colitis (ASUC)'), often within
the first year after diagnosis. Advances in therapy for UC with the availability of
effective biologics have revolutionized the medical care of UC, improving ability to
achieve remission and reducing the need for colectomy for refractory disease. However,
despite this general progress, investigators have not witnessed a corresponding temporal
improvement in disease outcomes among those with the most severe disease. As well,
providers lack the ability to 'personalize' care for UC by predicting up front which
patients may develop ASUC or fail medical therapy and may benefit from early surgery,
preventing protracted morbidity.
Over one-third of patients with ASUC will be refractory to intravenous steroids, the
cornerstone for initial management of this condition. Infliximab and cyclosporine, the
two most commonly used medical rescue therapies for this cohort, have comparable short-
and long-term efficacy in two randomized controlled trials. However, up to a third of
patients will not respond to such medical rescue. Lack of response is poorly understood
and may be multifactorial with both patient- and drug-related factors. Among the latter,
those with severe disease may have greater fecal loss of infliximab resulting in lack of
efficacy. Attempts to overcome this have included accelerated induction with infliximab
administered up front at a higher dose (10mg/kg) or more frequent intervals. A small
single center retrospective study of only 50 patients among whom 15 received accelerated
induction showed reduced short-term but not long-term rates of colectomy with this
approach. However, a robust and generalizable comparison of the two infliximab induction
treatment strategies are lacking. A key factor limiting study of ASUC is the lack of
availability of large cohorts with detailed clinical information and linked specimens.
Here, investigators will develop a large multi-center cohort of patients with ASUC with
homogeneously collected detailed longitudinal clinical and laboratory data. To the
investigators' knowledge, this will be the first of its kind in the United States, and
will be a key resource to understand the natural history, risk stratify and optimize
therapeutic algorithms for care of patients with ASUC. A sub-study with blood, stool and
biopsy specimens can be utilized for translational research into mechanisms of lack of
response and development of biomarkers. The infrastructure of this network will also
serve as a valuable resource for clinical trials of new therapies and novel strategies, a
significant unmet need.