Research Update on Crohn's and Ulcerative Colitis
This has been an active season for both Crohn’s Disease and Ulcerative Colitis research. Several papers looking at both biologicals and traditional treatments (Methotrexate) were published, and some new research on those with IBD and celiac disease was done. While there are many other interesting publications this quarter, these are a good cross-sampling of the good work being done to help those with IBD by medical researchers around the globe.
Researchers found that antibodies to Infliximab usually develop within the first 12 months of treatment if they are going to develop at all (90% of patients who developed them did so in that period). They also found that a loss of responsiveness to treatment may lag antibody development by several months. On the other hand, they found that immunomodulator therapy combined with infliximab maintained the drug’s effectiveness for a longer period in those who developed antibodies.
The research is important for both treatment choice and monitoring. It may make sense to monitor for antibody development for the first year and then stop monitoring unless other systems appear (or decrease the frequency). Additionally, if an individual develops antibodies, adding an immunomodulator to the regime becomes another option that may be better than switching to another anti-TNF-alpha drug in some cases.(1)
Anti-TNF-alpha Drugs and the Immune System
One of the frequent issues with Anti-TNF-alpha drugs is their impact on the immune system. There have been multiple studies that have shown rates of opportunistic infection appear to be higher with those on the biologicals. In a recent meta-analysis, the authors looked at opportunistic infections with those suffering from IBD and taking anti-TNF-alpha drugs v. placebo, including infections like herpes simplex, mycobacterium tuberculosis, and herpes zoster.
Overall, the rate of opportunistic infection rate of IBD patients on the biologicals was double that of those on placebo. While that sounds drastic, it is a measure of relative risk. If the overall risk of a given infection is still low, than doubling that risk may still be a low number. (2)
Celiac disease has recently received a lot of attention in the press in relation to gluten. While those suffering from celiac disease can’t tolerate gluten, the evidence doesn’t support a gluten-free diet for anyone else, including those with IBD. That said, there are individuals that have both IBD and celiac disease and suffer from their double whammy. Is there any difference in IBD presentation when an individual has both?
In new research, those with celiac disease and ulcerative colitis were found to be more likely to have pancolitis with an odds ratio of 3.3, and were more likely to use immunomodulators. Otherwise, there did not appear to be any greater impact to the IBD in patients with Crohn’s disease or in other aspects of ulcerative colitis. Finally, those with IBD were not at a higher risk for developing celiac disease, though those with celiac disease were at a higher risk for being diagnosed with IBD.(3)
Ulcerative Colitis and Methotrexate
Methotrexate has been a long-used second tier treatment for both Crohn’s and Ulcerative Colitis. The cost factors and availability make it more attractive than biologicals, but only if the other side of the cost-benefit equation is valid. Specifically for UC, there have been few prospective studies of the drug as an option for those who are resistant to or intolerant of thiopurines (e.g. 6-MP, AZA, 6-TG).
In a small-scale prospective study, researchers found methotrexate to not be effective in treating UC following thiopurine treatment failure, concluding “The efficacy of MTX in UC patients in this study was poor with a low clinical response rate (22%) and high colectomy rate (44%)”. The results were not promising, but the study itself was too small to be considered conclusive.(4)
· If patients on Remicade fail to develop antibodies in the first 12 months, the likelihood of doing so goes down dramatically.
· Anti-TNF-alpha drugs (the biologicals) double the risk for opportunistic infection in IBD patients.
· Celiac disease isn’t more likely if you have IBD, but if you have UC and celiac disease there is an increase pancolitis risk.
· Methotrexate, at least preliminarily, does not appear to be effective in treating UC, though bigger studies are needed for a definitive answer.
1. Ungar, Bella, Yehuda Chowers, Miri Yavzori, Orit Picard, Ella Fudim, Ofir Har-Noy, Uri Kopylov, Rami Eliakim, and Shomron Ben-Horin. "The temporal evolution of antidrug antibodies in patients with inflammatory bowel disease treated with infliximab." Gut (2013): gutjnl-2013.
2. Ford, Alexander C., and Laurent Peyrin-Biroulet. "Opportunistic Infections With Anti-Tumor Necrosis Factor-α Therapy in Inflammatory Bowel Disease: Meta-Analysis of Randomized Controlled Trials." The American journal of gastroenterology (2013).
3. Oxford, Emily C., Deanna D. Nguyen, Jenny Sauk, Joshua R. Korzenik, Vijay Yajnik, Sonia Friedman, and Ashwin N. Ananthakrishnan. "Impact of Coexistent Celiac Disease on Phenotype and Natural History of Inflammatory Bowel Diseases." The American journal of gastroenterology (2013).
4. Basuroy, R., H. E. Johnson, T. Hollingworth, S. A. Weaver, and S. D. McLaughlin. "PTH-093 Efficacy of Methotrexate in Ulcerative Colitis: A District General Hospital Experience." Gut 62, no. Suppl 1 (2013): A249-A249.