Sunday, August 4, 2013

IBD Research Update

Research Update


Time for the most recent research update.  There has been lots of great work in the IBD arena in the last quarter, and a few highlights are in order.  There are a mix of studies this quarter looking at both Crohn’s and Ulcerative Colitis (and in one case both).

Ulcerative Colitis and Anti-TNF alpha Drugs


The early Anti-tumor necrosis factor alpha drugs were primarily focused on Crohn’s disease for their initial indications.  Shortly after their demonstrated success in clinical trials with Crohn’s, trial began for the treatment of Ulcerative Colitis.  The UC treatment studies are less extensive than with Crohn’s, but a review showed that both infliximab and adalimumab were effective in promoting mucosal healing and improving quality of life.  The cross-trial success means that the Anti-TNF alpha drugs should be considered earlier in the treatment spectrum, and that there are further options available before colectomy. (1)

Intestinal Failure and Crohn’s Disease


The risk of intestinal failure is one of the greatest fears for those with Crohn’s disease.  A good predictive model of who will experience intestinal failure is not in place, but several predictive factors were identified in a small, retrospective review of case studies.  The review found that risk factors included an “earlier age at diagnosis, family history of inflammatory bowel disease, stricturing disease, younger age at first surgery, and operative complications”.  The higher risk factors may influence the use of more aggressive treatments or more frequent monitoring in specific patient populations.  Because new treatment modalities were not available when the early disease hit many in the study, these may not be predictive for more recently diagnosed patients .(2)

Stem Cells and Crohn’s Disease


The ASTIC trial (Autologous Stem Cell Transplantation International Crohn’s Disease) is one of the most ambitious clinical trials currently in progress in that it seeks to potentially cure Crohn’s disease and not simply induce and maintain remission (not that maintaining remission is anything most of us wouldn’t take seriously!)   The trial created a transplant group, which received a high risk bone marrow transplant of stem cells.  The control group was provided transplantation at 13 months.  45 patients were recruited, but 9 of the control group dropped out due to complications (all of the patients were moderate to severe with disease activity).  The initial results are excellent, as shown in the table below:

Parameter
Treatment Group, % (n = 22)
Control Group, % (n = 13)
Simple Endoscopic Score for Crohn's Disease of 0 (normal)
25
0
Simple Endoscopic Score for Crohn's Disease <5 (inactive or mild)
61
20
Complete mucosal healing
40
15
Segmental healing
58
30

There are still some words for caution.  First, the trial is small and the results are short term.  Second, and more importantly, the treatment is high risk – one patient died, likely from complications, in the treatment group, and all patients had failed with other immunosuppressants first.  The study definitely shows promise for further studies and refining the safety of the treatment regime if they pan out.(3)

Crohn’s, UC and BMI


Body Mass Index is a frequent (though controversial) measure of obesity.  In the large EPIC (European Prospective Investigation into Cancer and Nutrition) study, over 300,000 people were reviewed to determine if obesity as measured by BMI was a predictor for Crohn’s disease or Ulcerative Colitis.  Despite being a predictor for other conditions (such as Type II diabetes), the study found that there was no correlation between BMI and the incidence rates for either form of IBD.  This indicates that obesity is not associated strongly with developing IBD, or that BMI is a poor measure of obesity for this particular prediction.(4)

Bottom Line


·         The Anti-TNF alpha drugs have shown repeatedly to be a viable option for early, effective treatment of UC.
·         The likelihood of intestinal failure in Crohn’s is becoming better understood, and earlier, more severe symptoms tend to predict later failure.
·         Stem cell treatments are very high risk but potentially high reward, with small, initial results showing dramatic improvements in treating Crohn’s.
·         Obesity as measured by BMI is not associated with a higher risk of developing Crohn’s or UC.

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1.       Danese S, Colombel JF, Peyrin-Biroulet L, Rutgeerts P, Reinisch W. Review article: the role of anti-TNF in the management of ulcerative colitis -- past, present and future.  Alimentary Pharmacology and Therapeutics.  May, 2013.
2.       Predictors for developing intestinal failure in patients with Crohn's disease. Gearry RB, Kamm   MA, Hart AL, Bassett P, Gabe SM, Nightingale JM.J Gastroenterol Hepatol. 2013 May;28(5):801-7. doi: 10.1111/jgh.12115.

4.       Chan SS, Luben R, Olsen A, Tjonneland A, Kaaks R, Teucher B, Lindgren S, Grip O, Key T, Crowe FL, Bergmann MM, Boeing H, Hallmans G, Karling P, Overvad K, Palli D, Masala G, Kennedy H, vanSchaik F, Bueno-de-Mesquita B, Oldenburg B, Khaw KT, Riboli E, Hart AR.  Body mass index and the risk for Crohn's disease and ulcerative colitis: data from a European Prospective Cohort Study (The IBD in EPIC Study).  Am J Gastroenterol. 2013 Apr;108(4):575-82. doi: 10.1038/ajg.2012.453. Epub 2013 Jan 15.

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