Sunday, October 27, 2013

IBD in the Modern Age

Today's Treatment Regimes Come of Age


As the 1960’s passed into the 1970’s, medicine became more evidence-based and less experiential.  Regional Enteritis became Inflammatory Bowel Disease, and the suppositions that ulcerative colitis and Crohn’s disease were different disorders.  Over the next few decades, most of the major treatments now in use would be developed and the modern treatment regimen would slowly coalesce.

1970’s


The 1970’s built upon some of the discoveries of the 1960’s and increased the use of drugs originally developed for other purposes.  While there were still surgery-first advocates, medical interventions were on the rise and some of the first larger scales studies and epidemiological reviews were done.(1)

Diet became a large focus of treatment for IBD over the course of the decade.  Everything from elemental diets to low residue diets were proposed.  While these were viewed favorably, evidence was not in great supply.(2)  Some of the early work on high fiber diets also occurred in this decade.  These diets showed some promise and no increased formation of obstructions, but it would be another few decades before this idea began to take hold again.(3)  

Aside from the diet focus, there was a renewed interest in sulphasalazine for the treatment of IBD, primarily ulcerative colitis.  The efforts looked to quantify the optimal dosing based on defining the dose-response curve and minimizing the side effects.  The increased evidence-based focus led to the deprecation of sulphasalazine over the next decade in favor of drugs with similar efficacies but fewer side effects. (4,5)

1980’s


The decade that brought us hair bands and the first United States President to share the big screen with a chimpanzee also brought new classes of drugs to treat IBD.  Azodisal Sodium was investigated as a replacement for suphasalazine, and had a better safety profile.  It was found to be slightly better than the 5-ASA drugs, but with a higher level of side effects.  Though still a potentially viable drug, it is not regularly prescribed.(6)

Intravenous cyclosporine was similarly proposed as a treatment for ulcerative colitis, and worked well compared to placebo.  Cyclosporine was put forth as an alternative to 6-MP/Imuran for severe UC treatment, and was in use until the introduction of Infliximab and similar Anti-TNF drugs took hold.(7)

A new trend in dietary treatment of Crohn’s disease was engineered in the 1980’s (though the idea had been proposed earlier) – the use of the elemental diet.  The elemental diet consists of nutrients that are already broken down, requiring minimal work from the GI tract (or no work in the case of TPN).  Generally it is consumed by the patient, though a nasogastric tube can deliver it as well.  The efficacy is fairly high, and it is still in use, but the liver needs to be constantly monitored due to the offloading of some of the GI functions and patients sometimes have difficulty tolerating it.(8)

1990’s – Today


The modern era of IBD treatment has largely been focused on the anti-TNF alpha drugs.  Inflixmab hit the IBD world by storm in 1998, showing efficacy in the treatment of fistulae in Crohn’s disease patients without requiring surgery.(9) Adalimumab followed in 2008 for Cronh’s disease, and permitted anti-TNF treatment without needing an infusion.  Indications for ulcerative colitis came for Adalimumab in 2012.(10)  In the same year (2008), certolizumab was approved for the treatment of Crohn’s disease as well (though a UC treatment indication is still pending).(11)

There are innumerable research studies ongoing, and hopefully future treatments will bear as much fruit as those of the last decade for IBD.  While a cure is still not available, the treatment advances over the last few decades have enabled life-altering improvements for patients. 

Bottom Line


·         IBD treatment has changed dramatically over the years.  New treatments in the last decade have substantially improved outcomes.
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1.       Cooke, W. T., E. Mallas, P. Prior, and R. N. Allan. "Crohn's disease: course, treatment and long term prognosis." QJM 49, no. 3 (1980): 363-384.
2.       O'Morain, C., A. W. Segal, and A. J. Levi. "Elemental diets in treatment of acute Crohn's disease." British medical journal 281, no. 6249 (1980): 1173.
3.       Heaton, K. W., J. R. Thornton, and P. M. Emmett. "Treatment of Crohn's disease with an unrefined-carbohydrate, fibre-rich diet." British medical journal2, no. 6193 (1979): 764.
4.       Dissanayake, A. S., and S. C. Truelove. "A controlled therapeutic trial of long-term maintenance treatment of ulcerative colitis with sulphasalazine (Salazopyrin)." Gut 14, no. 12 (1973): 923-926.
5.       Khan, AK Azad, D. T. Howes, J. Piris, and S. C. Truelove. "Optimum dose of sulphasalazine for maintenance treatment in ulcerative colitis." Gut 21, no. 3 (1980): 232-240.
6.       Sandberg-Gertzen, H., G. Järnerot, and W. Kraaz. "Azodisal sodium in the treatment of ulcerative colitis. A study of tolerance and relapse-prevention properties." Gastroenterology 90, no. 4 (1986): 1024.
7.       Lichtiger, Simon, and DanielH Present. "Preliminary report: cyclosporin in treatment of severe active ulcerative colitis." The Lancet 336, no. 8706 (1990): 16-19.
8.       O'Moráin, C., A. W. Segal, and A. J. Levi. "Elemental diet as primary treatment of acute Crohn's disease: a controlled trial." British medical journal (Clinical research ed.) 288, no. 6434 (1984): 1859.
9.       Present, Daniel H., Paul Rutgeerts, Stephan Targan, Stephen B. Hanauer, Lloyd Mayer, R. A. Van Hogezand, Daniel K. Podolsky et al. "Infliximab for the treatment of fistulas in patients with Crohn's disease." New England Journal of Medicine 340, no. 18 (1999): 1398-1405.
10.   Reinisch, Walter, William J. Sandborn, Daniel W. Hommes, Geert D'Haens, Stephen Hanauer, Stefan Schreiber, Remo Panaccione et al. "Adalimumab for induction of clinical remission in moderately to severely active ulcerative colitis: results of a randomised controlled trial." Gut 60, no. 6 (2011): 780-787.

11.   Schreiber, Stefan, Mani Khaliq-Kareemi, Ian C. Lawrance, Ole Østergaard Thomsen, Stephen B. Hanauer, Juliet McColm, Ralph Bloomfield, and William J. Sandborn. "Maintenance therapy with certolizumab pegol for Crohn's disease." New England Journal of Medicine 357, no. 3 (2007): 239-250.

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