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.

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. 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.

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. 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. Intravenous steroids are used for cases refractory to oral steroids, or where oral steroids cannot be taken. 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 and for maintenance of remission in Crohn's disease. Formulated as Entocort, budesonide is released in the ileum and right colon, and is therefore has a topical effect against disease in that area.

Budesonide is also useful when used in combination with antibiotics for active Crohn's disease.

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.

Azathioprine and 6-MP have been found to be useful for the following indications:
 * For maintenance therapy for people who are dependent on steroids.
 * Fistulizing disease.
 * Induction of remission in steroid refractory disease.
 * Maintenance of remission after surgery for Crohn's disease.

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.
 * Induction of remission for people with Crohn's disease.
 * Maintenance for fistulizing Crohn's disease.

Side effects of infliximab include hypersensitivity and allergic reactions, risk of re-activation of tuberculosis, serum sickness, and risk of multiple sclerosis. 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. 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.

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. Fish oil has been found to be effective in reducing the chance of relapse in less severe cases. 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. 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 vitamin B absorption, people with Crohn's disease are at risk for B 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. 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.

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.

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.
 * 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. They are also used for treatment of complications, including abscesses and other infections accompanying Crohn's disease.
 * Thalidomide has shown response in reversing endoscopic evidence of disease.

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. 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).
 * Adalimumab, like infliximab is an antibody that targets tumour necrosis factor.
 * 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.
 * Natalizumab is an anti-integrin monoclonal antibody that shown utility as induction and maintenance treatment for moderate to severe Crohn's disease. However, it has been associated with progressive multifocal leukoencephalopathy, a usually fatal viral infection of the brain, that may limit its use.


 * Trichuris suis is a pig whipworm that been shown in one study to improve Crohn's disease symptoms.
 * Autologous stem cell transplant has also been evaluated.
 * 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.
 * 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, and Abbott is planning to initiate Phase IIb in 2007. The agent is also under investigation for the treatment of psoriasis.