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Unsuccessful Application: Example Eight


  • The paper is very descriptive.
  • The paper lacks criticism.
  • There is an inconsistent flow throughout the essay.


Essay: Methotrexate as a therapy for Crohn's disease


Crohn’s disease is classed as a chronic inflammatory disease which can have an effect on any section of the gastrointestinal tract. Crohn’s disease is a type of inflammatory disease, and often there can be difficulty in distinguishing between the two conditions (Roulis et al., 2011, 5396-5401). Generally, the disease will present symptoms from an early age, however it is still possible for the disease to be prevalent at any age. The average age for diagnosis is approximately 30 years. Individuals who suffer from the condition can suffer from diarrhoea, pain in the abdomen and loss of weight (National Institute for Health and Clinical Excellence, 2012). Studies have indicated that genetics play a large role in the onset on crohn’s disease. An individual who has a sibling with crohn’s disease, are thirty times more likely to develop the condition compared to the whole population. Thirty genes have been found to be related to the disease, and the biological pathway is known for most of the genes (Kaser et al., 2008, 743-756).


Treatment of Crohn’s Disease

There is no cure for crohn’s disease, however there are treatment and surgery options available which can maintain remission and prevent relapse (Travis et al., 2006, i16-i35). Glucocorticosteroids are commonly used to manage crohn’s disease, however patients have been found to become dependent on or resistant to the medication (Biancone et al., 2003, 31-37). Furthermore, long term use of the drug can lead to secondary conditions such as osteoporosis, diabetes and gaining of weight (Hanauer et al., 2002, 1541-1549).

Methotrexate is an anti-inflammatory cytotoxic drug which acts through dihydrofolate reductase inhibition (Feagan et al., 2000, 1627-1632). Previously the drug has been used for the successful treatment of rheumatoid arthritis, however more recently the use of the drug in crohn’s disease has shown potential. Suares et al (2011) investigated the used of methotrexate in patients who were not able to take thiopurines due to intolerance or lack of improvement. The study involved 66 patients, and all patients were classed as having active crohn’s disease (Lemann et al., 2000, 1730-1734). Interestingly the study found that methotrexate therapy was effective in the short term, up to four months, however over a longer period of time, the treatment was no longer effective. This suggests that the treatment is most effective in the early stages of the condition, and becomes less effective as the condition progresses.



Crohn’s disease is a chronic condition which is characterised by relapses. The exact cause of the disease still remains unclear; however it is likely that the disease is triggered by environmental factors as well as genetic predisposition. The combination of environmental and genetic factors, can lead to the immune system attacking the gastrointestinal tract which has been suggested to be directed at microbial antigens. There are numerous treatment options for crohn’s disease, with methotrexate being a common drug. Methotrexate is classed as an immunosuppressant, however there is still some confusion in the literature about its efficacy.



Biancone, L., Tosti, C., Fina, D., Fantini, M., De Nigris, F., Geremia, A. & Pallone, F. 2003. Review article: maintenance treatment of Crohn's disease. Aliment Pharmacol Ther, 17, 31-37.

Feagan, B. G., Fedorak, R. N., Irvine, E. J., Wild, G., Sutherland, L., Steinhart, A. H., Greenberg, G. R., Koval, J., Wong, C. J., Hopkins, M., Hanauer, S. B. & Mcdonald, J. W. D. 2000. A Comparison of Methotrexate with Placebo for the Maintenance of Remission in Crohn's Disease. New England Journal of Medicine, 342, 1627-1632.

Hanauer, S. B., Feagan, B. G., Lichtenstein, G. R., Mayer, L. F., Schreiber, S., Colombel, J. F., Rachmilewitz, D., Wolf, D. C., Olson, A., Bao, W. & Rutgeerts, P. 2002. Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. The Lancet, 359, 1541- 1549.

Kaser, A., Lee, A.-H., Franke, A., Glickman, J. N., Zeissig, S., Tilg, H., Nieuwenhuis, E. E. S., Higgins, D. E., Schreiber, S., Glimcher, L. H. & Blumberg, R. S. 2008. XBP1 Links ER Stress to Intestinal Inflammation and Confers Genetic Risk for Human Inflammatory Bowel Disease. Cell, 134, 743-756.

Lemann, M., Zenjari, T., Bouhnik, Y., Cosnes, J., Mesnard, B., Rambaud, J.-C., Modigliani, R., Cortot, A. & Colombel, J.-F. 2000. Methotrexate in Crohn's disease: long-term efficacy and toxicity. Am J Gastroenterol, 95, 1730-1734.

National Institute for Health and Clinical Excellence 2012. Crohn's disease. Roulis, M., Armaka, M., Manoloukos, M., Apostolaki, M. & Kollias, G. 2011. Intestinal epithelial cells as producers but not targets of chronic TNF suffice to cause murine Crohn-like pathology. Proceedings of the National Academy of Sciences, 108, 5396- 5401.

Travis, S. P. L., Stange, E. F., Lémann, M., Öresland, T., Chowers, Y., Forbes, A., D’haens, G., Kitis, G., Cortot, A., Prantera, C., Marteau, P., Colombel, J.-F., Gionchetti, P., Bouhnik, Y., Tiret, E., Kroesen, J., Starlinger, M. & Mortensen, N. J. 2006. European evidence based consensus on the diagnosis and management of Crohn’s disease: current management. Gut, 55, i16-i35.