Tumor Necrosis Factor Alpha Inhibitor (Lnfliximab, Adalimumab) Treatment for Crohn'S-like Inflammatory Bowel Disease in Chronic Granulomatous Disease: A Phase I/II Study Assessing Clinical and Immune Responses to Treatment and Genetic Influences
Chronic Granulomatous Disease (CGD) is an inherited immune disorder involving decreased
phagocytic superoxide oxygen radical production, resulting in increased susceptibility to
infections. Furthermore, there is a predominance of immune-related inflammatory problems in
a subset of CGD patients, such as the inflammatory bowel disease (CGD-IBD). CGD-IBD is often
complicated by obstruction, strictures, fissures, fistulae, and extra-intestinal problems.
In fact, it is clinically and histologically indistinguishable from Crohn's Disease (CD),
another inflammatory bowel disease that affects the general population. Crohn's disease (CD)
is a prototypic T helper cell type 1 (Th1) immune disease. Since CGD-IBD bears such close
resemblance to CD, it is possible that CGD-IBD is also immune-based. Furthermore, mice
studies also support a primarily immune basis for CGD-IBD. However, currently there is
little data on this Crohn's-like CGD-IBD in human patients. Treatment for the Crohn's-like
CGD-IBD has been primarily oral or topical corticosteroids. Antibiotics have been
ineffective and stool cultures typically do not identify clear pathogens. Many patients with
the Crohn's-like CGD-IBD disease remain steroid-dependent, thus new therapeutic regimens are
This is a Phase I/II study that will evaluate the safety and efficacy of Tumor Necrosis
Factor Alpha Inhibitor (Infliximab or Adalimumab) in CGD patients with symptomatic
Crohn's-like IBD. Infliximab and Adalimumab are standard-of-care treatments for moderate to
severe CD, with extensive experience using these agents being well documented in terms of
safety and efficacy. Preliminary reports from ongoing studies of CD at NIH are encouraging
in inducing remission. We will also evaluate changes in immunophenotype and cytokine
profiles of peripheral blood and colonic lamina propria lymphocytes following treatment. In
addition, we will evaluate the immunophenotype and cytokine profile of blood and mucosal
cells in CGD patients, with or without IBD, to determine the CGD-specific cytokine profile.
Specific cytokine profiles have been observed in different genetic immunodeficiencies,
despite similar IBD clinical manifestation.
Documentation of clinical status will be performed using the Crohn's Disease Activity Index
(CDAI). Potential effects of genetic variation (including CGD mutation type) on the
expression of IBD in patients with CGD, and their responses to treatment will also be
assessed. The long-term goal of this study is to establish better or alternative treatment
modalities with low risk profiles for CGD patients with Crohn's-like IBD.
Endpoint Classification: Safety/Efficacy Study, Masking: Open Label, Primary Purpose: Treatment
To determine whether treatment with infliximab is safe in CGD patients and does not cause a significant increase in serious infections.
Caryn G Morse, M.D.
National Institutes of Health Clinical Center (CC)
United States: Federal Government
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