Cancer Treatment Today » Crohn’s Disease and Ulcerative Colitis

Stem and mesenchymal cell transplantation for Crohn’s disease and Ulcerative colitis – pro

M Levin, MD — Sun, 02 Sep 2012 13:01:04 +0000

The incidence and prevalence of Crohn’s disease (CD) and ulcerative colitis (UC), the two major forms of inflammatory bowel diseases (IBD), are rising in western countries. At the same time, stem cell therapies are gaining a prominent place of interest among clincal investigator. at this time, only phase I studies have been performed and are ongoing in patients with Crohn’s disease. Clinical improvements in some IBD patients have been reported after allogeneic and autologous transplantation of stem cells. In addition, various paremeters of immune functions have improved or normalized in several reported patients.

Experimental and clinical data indicate that both hematopoietic and mesenchymal stem cells(MSC, which are present in the marrow or are marrow derived, have great potential for those clinical applications that require tissue regeneration or repair promotion, owing to their plasticity and their immunomodulatory properties. Bone marrow transplantation from an unaffected donor is able to ameliorate pathology in a mouse model of chronic genetic-based colitis. Moreover, CD34- bone marrow- and peripheral blood-derived stem cells contributed to mucosal repair via neoangiogenesis in moderate-severe murine colitis and were effective in reducing the pathologic features associated with IBD. Both HSC and MSC transplantation in IBD are currently being evaluated in Phase III clinical trials.

Giacomo Lanzoni, Giulia Roda, Andrea Belluzzi, Enrico Roda, and Gian Paolo Bagnara Inflammatory bowel disease: Moving toward a stem cell-based therapy World J Gastroenterol. 2008 August 7; 14(29): 4616–4626.

Julián Panés et al, Mesenchymal stem cell therapy of Crohn’s disease: are the far-away hills getting closer?
Gut 2011;60:742-744

Stem cell transplantation for Crohn’s – pro

M Levin, MD — Tue, 28 Aug 2012 00:56:11 +0000

Crohn’s disease (CD) is an inflammatory bowel disorder that involves loss of immune tolerance in the gastrointestinal tract and T helper 1 delayed-type hypersensitivity of the gut wall, frequently resulting in granuloma formation. The molecular defect causing CD has not been characterized, but probably involves aberrant T cell function. Although CD often responds to immunosuppressive medication including corticosteroids, azathioprine and 6-mercaptopurine, to anti inflammatory drugs such as 5 aminosalicylate (5 ASA), or to some antimicrobial agents, including metronidazole, no therapy has been curative. Hematopoietic stem cell transplantation (HSCT) is being evaluated as an option for patients with refractory CD. There are several phase II studies and the randomized trial of autologous non-myeloablative therapy vs. standard treatment. There have been several reported cases in which HSCT was used to treat patients with refractory CD and cases involving patients with CD who underwent stem cell transplantation for other reasons. These studies showed varying remission of CD, both clinically and histologically.Hawkey CJ. Stem cell transplantation for Crohn’s disease. Best Pract Res Clin Haematol. 2004;17(2):317-325.
Oyama Y, Craig RM, Traynor AE, et al. Autologous hematopoietic stem cell transplantation in patients with refractory Crohn’s disease. Gastroenterology. 2005;128(3):552-563.
Lopez-Cubero SO, Sullivan KM, McDonald GB. Course of Crohn’s disease after allogeneic marrow transplantation. Gastroenterology. 1998;114(3):433-440.
Ditschkowski M, Einsele H, Schwerdtfeger R, et al. Improvement of inflammatory bowel disease after allogeneic stem-cell transplantation. Transplantation. 2003;75(10):1745-1747.
Hinterberger W, Hinterberger-Fischer M, Marmont A. Clinically demonstrable anti-autoimmunity mediated by allogeneic immune cells favorably affects outcome after stem cell transplantation in human autoimmune diseases. Bone Marrow Transplant. 2002;30(11): 753-759.
Kashyap A, Forman SJ. Autologous bone marrow transplantation for non-Hodgkin’s lymphoma resulting in long-term remission of coincidental Crohn’s disease. Br J Haematol. 1998;103(3):651-652.
Scime R, Cavallaro AM, Tringali S, et al. Complete clinical remission after high-dose immune suppression and autologous hematopoietic stem cell transplantation in severe Crohn’s disease refractory to immunosuppressive and immunomodulator therapy. Inflamm Bowel Dis. 2004;10(6):892-894.

Crohn’s disease and B12 – pro

M Levin, MD — Thu, 23 Aug 2012 02:18:30 +0000

Crohn’s disease(CD) is a chronic inflammatory condition of the intestine, which can cause damage to the portion of the small intestine where vitamin B12 is absorbed and result in B12 deficiency. There is evidence that taking vitamin B12 supplementation may help to improve low levels caused by Crohn’s disease.

However, B12 deficeincy is not inevitable. In a recent study(2010), 22% of CD pateints had low B12 levels.In CD patients, prior small intestinal surgery is an independent risk factor for having a low serum vitamin B12 level.

In general, when B12 deficiency is diagnosed, it should be treated. Routine prophylaxis with B12 is not recommended by guidelines.

http://www.acg.gi.org/physicians/guidelines/CrohnsDiseaseinAdults2009.pdf

Mustafa Yakut et al, Serum vitamin B12 and folate status in patients with inflammatory bowel diseases European Journal of Internal Medicine Volume 21, Issue 4 , Pages 320-323, August 2010

Humira for Ulcerative Colitis – pro

M Levin, MD — Fri, 03 Aug 2012 02:36:27 +0000

Adalimumab(Humira) is an anti-tumor necrosis factor (TNF) agent that is approved for both inducing and maintaining remission in moderately to severely active Crohn’s disease. Small open-label trials and case reports suggest that it can induce responses in both anti-TNF-naive and anti-TNF-treated patients with active ulcerative colitis. This led to a phase III trial sponsored by Abott. In it, of the 248 patients treated with 40mg every other week, 16.5 percent achieved clinical remission compared to 9.3 percent on placebo at week 8 p=0.019). At week 52, 17.3 percent achieved clinical remission compared to 8.5 percent on placebo (p=0.004). These results were statistically significant compared to placebo. The safety results was as expected from Humira.

On April 11, 2012 the European Commission has approved HUMIRA® (adalimumab) for the treatment of moderately to severely active ulcerative colitis (UC) in adult patients who have had an inadequate response to conventional therapy. In the USA, in May 2012, Humira is approved for: Rheumatoid Arthritis, Juvenile Idiopathic Arthritis, Psoriatic Arthritis, Ankylosing Spondylitis, Crohn’s Disease, Plaque Psoriasis but not ulceratuve colitis.

Alessandro Armuzzi & Daniela Pugliese IBD: Adalimumab for ulcerative colitis—is the glass half empty or half full? Nature Reviews Gastroenterology and Hepatology 8, 249-251 (May 2011)

Humira, Prescribing Information, 2012

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