Treatment of Crohn's disease
Overview
The treatment of Crohn's disease is sequential: to treat acute disease, and then to maintain remission. Treatment initially involves the use of medications to treat any infection and to reduce inflammation. This usually involves the use of aminosalicylate anti-inflammatory drugs and corticosteroids, and may include antibiotics. Surgery may be required for complications such as obstructions or abscesses, or if the disease does not respond to drugs within a reasonable time.
Once remission is induced, the goal of treatment becomes maintenance of remission, avoiding the return of active disease, or "flares". Because of side-effects, the prolonged use of corticosteroids must be avoided. Although some people are able to maintain remission with aminosalicylates alone, many require immunosuppressive drugs. [1]
Aminosalicylate anti-inflammatory drugs
5-aminosalicylates (5-ASA) include the following:
- Mesalazine or mesalamine, which is marketed in the forms Asacol, Pentasa, Salofalk, Dipentum and Rowasa.
- Sulfasalazine, which is converted to 5-ASA and sulfapyridine by intestinal bacteria. The sulfapyridine may have some therapeutic effect in addition to the 5-ASA, although this is not entirely clear.
5-ASA compounds have been shown to be useful in the treatment of mild-to-moderate Crohn's disease.[2] They are usually considered to be first line therapy for disease in the ileum and right side of the colon particularly due to their low side effect profile.[3]
Corticosteroid anti-inflammatory drugs
Corticosteroids are a class of anti-inflammatory drug that are used primarily for treatment of moderate to severe flares of Crohn's disease. They are used more sparingly due to the availability of effective treatments with less side-effects.[4] The side effects of corticosteroids include Cushing's syndrome, mania, insomnia, hypertension, high blood glucose, osteoporosis, and avascular necrosis of long bones. These should not be confused with the anabolic steroids used to enhance athletic performance.
The most commonly prescribed oral steroid is prednisone, which is typically dosed at 0.5 mg/kg for induction of remission.[5] Intravenous steroids are used for cases refractory to oral steroids, or where oral steroids cannot be taken.[4] These are administered in the hospital setting. Because corticosteroids reduce the ability to fight infection, care must be used to ensure that there isn't an active infection, particularly an intra-abdominal abscess before the initiation of steroids.
Budesonide is an oral corticosteroid with limited absorption and high level of first-pass metabolism, meaning that less quantities of steroid enter into the bloodstream. It has been shown to be useful in the treatment of mild-to-moderate Crohn's disease[6] and for maintenance of remission in Crohn's disease.[7] Formulated as Entocort, budesonide is released in the ileum and right colon, and is therefore has a topical effect against disease in that area.[6]
Budesonide is also useful when used in combination with antibiotics for active Crohn's disease.[8]
Steroid enemas can also be used for disease of the lower colon and rectum, in order to treat symptoms. Hydrocortisone and budesonide liquid and foam enemas are being marketed for these reasons.
Mercaptopurine immunosuppressing drugs
Azathioprine and 6-mercaptopurine (6-MP) are the most used immunosuppressants for maintenance therapy of Crohn's disease. They are purine anti-metabolites, meaning that they interfere with the synthesis of purines required for inflammatory cells. They have a duration of action of months, making it unwieldy to use them for induction of remission. Both drugs are dosed at 1.5 to 2.5 mg/kg, with literature supporting the use of higher doses.[9]
Azathioprine and 6-MP have been found to be useful for the following indications:
- For maintenance therapy for people who are dependent on steroids.[10]
- Fistulizing disease.[11]
- Induction of remission in steroid refractory disease.[12]
- Maintenance of remission after surgery for Crohn's disease.[13]
Infliximab
- Main article: Infliximab, Biological therapy for inflammatory bowel disease
Infliximab, marketed as Remicade, is a mouse-human chimeric antibody that targets tumour necrosis factor, a cytokine in the inflammatory response. It is administered intravenously and dosed per weight.
Infliximab has found utility as follows:
- Maintenance of remission for people with Crohn's disease.[14]
- Induction of remission for people with Crohn's disease.[14]
- Maintenance for fistulizing Crohn's disease.[15]
Side effects of infliximab include hypersensitivity and allergic reactions, risk of re-activation of tuberculosis, serum sickness, and risk of multiple sclerosis.[16] Serious side effect include lymphoma and severe infections.
Surgery
Surgery is generally reserved for complications of Crohn's disease, or when disease that resists treatment with drugs is confined to one location that can be removed.[17] Surgery is often used to manage complications of Crohn's disease, including fistulae, small bowel obstruction, colon cancer, small intestine cancer and fibrostenotic strictures, when strictureplasty (expansion of the stricture) is sometimes performed. Otherwise, and for other complications, resection and anastomosis - the removal of the affected section of intestine and the rejoining of the healthy sections - is the surgery usually performed for Crohn's disease (e.g., ileocolonic resection). Neither type of surgery cures Crohn's disease, as recurrence often reappears in previously unaffected areas of the intestine.[18]
Small intestine transplants are experimental as of yet, and are usually only done when there is a risk of short bowel syndrome due to repeated resection surgeries.
Diet and lifestyle
There is no evidence that diet causes or cures Crohn's disease. If a person with Crohn's finds that certain foods increase or decrease the symptoms, then they may adjust their diet accordingly. A food diary is recommended to see what positive or negative effects particular foods have [2]. Fish oil has been found to be effective in reducing the chance of relapse in less severe cases.[19] People with lactose intolerance due to small bowel disease may benefit from avoiding lactose-containing foods. Many diets have been proposed for treatment of Crohn's disease, and many do improve symptoms, but none have been proven to actually cure Crohn's disease.[20] A low residue diet may be used to reduce the volume of stools excreted daily. Stress is not proven to aggravate or induce the symptoms of Crohn’s disease. If sufferers observe that Stress Management is a successful method of suppressing the illness in their bodies, then they may manage stress as they see fit. Conversely, stress is likely to be caused by the flaring up of the disease and this would make day to day life more difficult. Smoking has also been noted to have an association with Crohn's, and smokers with Crohn's are encouraged to quit.
Because the terminal ileum is the most common site of involvement and is the site for [[Cyanocobalamin|vitamin BTemplate:Ssub]] absorption, people with Crohn's disease are at risk for BTemplate:Ssub deficiency and may need supplementation. In cases with extensive small intestine involvement, the fat soluble vitamins A, D, E and K can be deficient. Folate deficiency is a risk when being treated with methotrexate.
Complementary and alternative medicine
More than half of Crohn's disease sufferers have tried complementary or alternative therapy.[21] These include diets, probiotics, fish oil and other herbal and nutritional supplements. The benefit of these medications is uncertain.
Traditional Chinese medicine can be used to help manage the symptoms of Crohn's disease.[22]
Helminthic therapy has been shown to achieve remission for 73% of patients, patients who were otherwise non-refractive to traditional therapies. The research subjects remained on their traditional therapies for the duration of the study, so at this time this therapy is an adjunct to existing treatments. Due to the unconventional nature of this therapy, despite its efficacy, it is not widely used.
Regular dosis of Absinth have been found to help to decrease sympthoms and aschieve better remissions in 2007 studies in Munich, Germany. [23]
Other medications
- Methotrexate is a folate anti-metabolite drug which is also used for chemotherapy. It is useful in maintenance of remission for those no longer taking corticosteroids.[24]
- Metronidazole and ciprofloxacin are antibiotics which are used to treat Crohn's that have colonic or perianal involvement, although this use is non-Food and Drug Administration (FDA) approved.[25] They are also used for treatment of complications, including abscesses and other infections accompanying Crohn's disease.[4]
- Thalidomide has shown response in reversing endoscopic evidence of disease.[26]
Research on medications in progress
Many clinical trials have been recently completed or are ongoing for new therapies for Crohn's disease. They include the following:
- Sargramostim, or granulocyte-monocyte colony stimulating factor (GM-CSF) has been shown to substabtially improve health-related quality of life in pilot studies, measured by an increase in score of a 32-item IBD questionnaire. [27] A recent Phase II trial showed that Sargramostim significantly decreased CD severity (48% compared to 26% placebo group) and improved quality of life (40% versus 19% for placebo).[28]
- Adalimumab, like infliximab is an antibody that targets tumour necrosis factor.[29]
- Certolizumab is a PEGylated Fab fragment of a humanized anti-TNF alpha monoclonal antibody that was found to have efficacy over placebo in one large trial.[30]
- Natalizumab is an anti-integrin monoclonal antibody that shown utility as induction and maintenance treatment for moderate to severe Crohn's disease.[31] However, it has been associated with progressive multifocal leukoencephalopathy, a usually fatal viral infection of the brain, that may limit its use.[32]
- Trichuris suis is a pig whipworm that been shown in one study to improve Crohn's disease symptoms.[33]
- Autologous stem cell transplant has also been evaluated .[34]
- Rifabutin, clarithromycin and clofazimine are antibiotics designed to attack mycobacterium avium subsp. paratuberculosis, which may be a cause of Chron's disease. This treatment, called Myoconda, is being tested by Giaconda.
- Necator Americanus is a helminth that, like pig whip worm, is being studied for efficacy in the treatment of Crohn's having already been proven effective (66% remission rate) against asthma. [35]
- ABT-874 is a human anti-IL-12 monoclonal antibody being developed by Abbott Laboratories in conjunction with Cambridge Antibody Technology for the treatment of multiple autoimmune diseases including Crohn's disease. Phase II trials have been completed and showed promising results,[36] and Abbott is planning to initiate Phase IIb in 2007.[37] The agent is also under investigation for the treatment of psoriasis.
References
- ↑ Management of Crohn's Disease in Adults, Am. J. Gastroenterology, Vol 96, No. 3[1]
- ↑ Hanauer SB, Stromberg U. Oral Pentasa in the treatment of active Crohn's disease: A meta-analysis of double-blind, placebo-controlled trials. Clin Gastroenterol Hepatol. 2004 May;2(5):379-88. PMID 15118975
- ↑ Prantera C, Cottone M, Pallone F, Annese V, Franze A, Cerutti R, Bianchi Porro G. Mesalamine in the treatment of mild to moderate active Crohn's ileitis: results of a randomized, multicenter trial. Gastroenterology. 1999 Mar;116(3):521-6. PMID 10029609.
- ↑ 4.0 4.1 4.2 Gopal, Latha (2006-05-23). "Crohn Disease". eMedicine. Retrieved 2006-07-02. Unknown parameter
|coauthors=ignored (help); Check date values in:|date=(help) - ↑ Hanauer SB. Sulfasalazine vs. steroids in Crohn's disease: David vs. Goliath? Gastroenterology. 1991 Oct;101(4):1130-1. PMID 1679735.
- ↑ 6.0 6.1 Greenberg GR, Feagan BG, Martin F, Sutherland LR, Thomson AB, Williams CN, Nilsson LG, Persson T. Oral budesonide for active Crohn's disease. Canadian Inflammatory Bowel Disease Study Group. N Engl J Med. 1994 Sep 29;331(13):836-41.
- ↑ Sandborn WJ, Lofberg R, Feagan BG, Hanauer SB, Campieri M, Greenberg GR. Budesonide for maintenance of remission for people with Crohn's disease in medically induced remission: a predetermined pooled analysis of four randomized, double-blind, placebo-controlled trials. Am J Gastroenterol. 2005 Aug;100(8):1780-7. PMID 16086715
- ↑ Steinhart AH, Feagan BG, Wong CJ, Vandervoort M, Mikolainis S, Croitoru K, Seidman E, Leddin DJ, Bitton A, Drouin E, Cohen A, Greenberg GR. Combined budesonide and antibiotic therapy for active Crohn's disease: a randomized controlled trial. Gastroenterology. 2002 Jul;123(1):33-40. PMID 12105831.
- ↑ Podolsky, Daniel K. (2002). "Inflammatory bowel disease". New England Journal of Medicine. 346 (6): 417–29. PMID 12167685. Retrieved 2006-07-02. Unknown parameter
|month=ignored (help) - ↑ Rosenberg JL, Levin B, Wall AJ, Kirsner JB. A controlled trial of azathioprine in Crohn's disease. Am J Dig Dis. 1975 Aug;20(8):721-6. PMID 1098449
- ↑ Dejaco C, Harrer M, Waldhoer T, Miehsler W, Vogelsang H, Reinisch W. Antibiotics and azathioprine for the treatment of perianal fistulas in Crohn's disease. Aliment Pharmacol Ther. 2003 Dec;18(11-12):1113-20. PMID 14653831
- ↑ Sandborn W, Sutherland L, Pearson D, May G, Modigliani R, Prantera C. Azathioprine or 6-mercaptopurine for inducing remission of Crohn's disease. Cochrane Database Syst Rev. 2000;(2):CD000545. PMID 10796557
- ↑ Hanauer SB, Korelitz BI, Rutgeerts P, Peppercorn MA, Thisted RA, Cohen RD, Present DH. Postoperative maintenance of Crohn's disease remission with 6-mercaptopurine, mesalamine, or placebo: a 2-year trial. Gastroenterology. 2004 Sep;127(3):723-9. PMID 15362027.
- ↑ 14.0 14.1 Hanauer SB, Feagan BG, Lichtenstein GR, Mayer LF, Schreiber S, Colombel JF, Rachmilewitz D, Wolf DC, Olson A, Bao W, Rutgeerts P; ACCENT I Study Group. Maintenance infliximab for Crohn's disease: the ACCENT I randomised trial. Lancet. 2002 May 4;359(9317):1541-9. PMID. 12047962
- ↑ Sands BE, Anderson FH, Bernstein CN, Chey WY, Feagan BG, Fedorak RN, Kamm MA, Korzenik JR, Lashner BA, Onken JE, Rachmilewitz D, Rutgeerts P, Wild G, Wolf DC, Marsters PA, Travers SB, Blank MA, van Deventer SJ. Infliximab maintenance therapy for fistulizing Crohn's disease. N Engl J Med. 2004 Feb 26;350(9):876-85. PMID 14985485
- ↑ Rutgeerts P, Van Assche G, Vermeire S. Review article: Infliximab therapy for inflammatory bowel disease--seven years on. Aliment Pharmacol Ther. 2006 Feb 15;23(4):451-63. PMID 16441465.
- ↑ Hanauer, Stephen B. (1996). "Inflammatory bowel disease". New England Journal of Medicine. 334 (13): 841–848. PMID 8596552. Retrieved 2006-11-10. Unknown parameter
|month=ignored (help) - ↑ "Surgery for Crohn's Disease". Crohn's and Colitis Foundation of America. 2006. Retrieved 2006-06-08. Unknown parameter
|month=ignored (help) - ↑ A Belluzzi, C Brignola, M Campieri, A Pera, S Boschi, and M Miglioli (1996). "Effect of an Enteric-Coated Fish-Oil Preparation on Relapses in Crohn's Disease". New England Journal of Medicine. 334 (24): 1557–60. Unknown parameter
|month=ignored (help) - ↑ Gottschall, Elaine (1994). Breaking the Vicious Cycle: Intestinal Health Through Diet. Baltimore: Kirkton Press. ISBN 0-9692768-1-8.
- ↑ Caprilli R, Gassull M, Escher J; et al. "European evidence based consensus on the diagnosis and management of Crohn's disease: special situations". Gut. 55 Suppl 1: i36–58. PMID 16481630.
- ↑ http://www.acupuncturetoday.com/archives2001/jan/01chen.html Two part review of Western approach versus Eastern approach to managing Crohn's disease
- ↑ Scientific journal Münchner Medizinische Wochenschrift (MMW) Journal 33-34 Year 2007 Page 23
- ↑ Feagan BG, Fedorak RN, Irvine EJ, Wild G, Sutherland L, Steinhart AH, Greenberg GR, Koval J, Wong CJ, Hopkins M, Hanauer SB, McDonald JW. A comparison of methotrexate with placebo for the maintenance of remission in Crohn's disease. North American Crohn's Study Group Investigators. N Engl J Med. 2000 Jun 1;342(22):1627-32. PMID 10833208
- ↑ Ursing B, Alm T, Barany F, Bergelin I, Ganrot-Norlin K, Hoevels J, Huitfeldt B, Jarnerot G, Krause U, Krook A, Lindstrom B, Nordle O, Rosen A. A comparative study of metronidazole and sulfasalazine for active Crohn's disease: the cooperative Crohn's disease study in Sweden. II. Result. Gastroenterology. 1982 Sep;83(3):550-62. PMID 6124474
- ↑ Cohen LB. Re: Disappearance of Crohn's ulcers in the terminal ileum after thalidomide therapy. Can J Gastroenterol 2004; 18(2): 101-104. Can J Gastroenterol. 2004 Jun;18(6):419. PMID 15230268.
- ↑ Korzenik JR, Dieckgraefe BK, Valentine JF, Hausman DF, Gilbert MJ; Sargramostim in Crohn's Disease Study Group. Sargramostim for active Crohn's disease. N Engl J Med. 2005 May 26;352(21):2193-201. PMID 15917384.
- ↑ B. Dieckgraefe (2006). "Improving Mucosal Barrier Function - A Novel Therapeutic Strategy for Crohn's Disease".
- ↑ Hanauer SB, Sandborn WJ, Rutgeerts P, Fedorak RN, Lukas M, MacIntosh D, Panaccione R, Wolf D, Pollack P. Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn's disease: the CLASSIC-I trial. Gastroenterology. 2006 Feb;130(2):323-33. PMID 16472588
- ↑ Schreiber S, Rutgeerts P, Fedorak R, Khaliq-Kareemi M, Kamm M, Boivin M, Bernstein C, Staun M, Thomsen O, Innes A (2005). "A randomized, placebo-controlled trial of certolizumab pegol (CDP870) for treatment of Crohn's disease". Gastroenterology. 129 (3): 807–18. PMID 16143120.
- ↑ Sandborn W, Colombel J, Enns R, Feagan B, Hanauer S, Lawrance I, Panaccione R, Sanders M, Schreiber S, Targan S, van Deventer S, Goldblum R, Despain D, Hogge G, Rutgeerts P (2005). "Natalizumab induction and maintenance therapy for Crohn's disease". N Engl J Med. 353 (18): 1912–25. PMID 16267322.
- ↑ Van Assche G, Van Ranst M, Sciot R, Dubois B, Vermeire S, Noman M, Verbeeck J, Geboes K, Robberecht W, Rutgeerts P (2005). "Progressive multifocal leukoencephalopathy after natalizumab therapy for Crohn's disease". N Engl J Med. 353 (4): 362–8. PMID 15947080.
- ↑ Summers RW, Elliott DE, Urban JF Jr, Thompson R, Weinstock JV. Trichuris suis therapy in Crohn's disease. Gut. 2005 Jan;54(1):87-90. PMID 15591509.
- ↑ Oyama Y, Craig RM, Traynor AE, Quigley K, Statkute L, Halverson A, Brush M, Verda L, Kowalska B, Krosnjar N, Kletzel M, Whitington PF, Burt RK. Autologous hematopoietic stem cell transplantation for people with refractory Crohn's disease. Gastroenterology. 2005 Mar;128(3):552-63.PMID 15765390
- ↑ Paul J. Fortun, BM BCh BMRP IBD-0184
- ↑ Mannon PJ et al. (2004) Anti–interleukin-12 antibody for active Crohn's disease N Engl J Med 351: 2069–2079
- ↑ http://www.cambridgeantibody.com/home/products/licensed_products/abbott/abt874
See also
Template:Crohn's Template:Gastroenterology
de:Morbus Crohn it:Morbo di Crohn he:מחלת קרוהן nl:Ziekte van Crohn no:Crohns sykdom simple:Crohn's disease sk:Crohnova choroba fi:Crohnin tauti sv:Crohns sjukdom