Management of Crohn's disease involves first treating the acute symptoms of the disease, then maintaining remission. Since Crohn's disease is an immune system condition, it cannot be cured by medication or surgery. Treatment initially involves the use of medications to eliminate infections (generally antibiotics) and reduce inflammation (generally aminosalicylate anti-inflammatory drugs and corticosteroids). Surgery may be required for complications such as obstructions, fistulae, abscesses, or if the disease does not respond to drugs within a reasonable time. However, surgery cannot cure Crohn's disease. This involves removing the affected part of the intestine and reconnecting the healthy sections. However, the disease often returns even after surgery. 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 is avoided. Although some people are able to maintain remission spontaneously, many require immunosuppressive drugs.
Aminosalicylates 5-ASA compounds, such as mesalazine and sulfasalazine, have shown to be of very little efficacy in the treatment of Crohn's disease, either for induction or for maintenance of remission. Current guidelines do not advise the use of 5-ASA compounds in Crohn's disease.
Corticosteroids
Corticosteroids are a class of anti-inflammatory drugs used to treat moderate to severe flares of Crohn's disease. However, they are used sparingly because they can cause serious side effects, including Cushing's syndrome, mania, insomnia, hypertension, high blood glucose, osteoporosis, and avascular necrosis of long bones. Corticosteroids 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 in Crohn's disease. Intravenous steroids, administered in a hospital setting, are used when oral steroids do not work or cannot be taken. Because corticosteroids reduce the body's ability to fight infection, care must be taken to ensure that there is no active infection, particularly an intra-abdominal abscess, before the initiation of steroids. Another oral corticosteroid, budesonide (trade name Entocort), has limited absorption and a high level of first-pass metabolism, meaning that lower quantities of the drug enter the bloodstream. It has been shown to be useful in the treatment of mild to moderate Crohn's disease, and in maintaining remission. It is also effective when used in combination with antibiotics to treat active Crohn's disease. Budesonide is released in the ileum and right colon, and therefore has a topical effect against disease in that area. Steroid enemas can also be used to treat symptoms in the lower colon and rectum. Hydrocortisone and budesonide liquid and foam enemas are marketed for this purpose.
Mercaptopurine immunosuppressing drugs
Azathioprine and 6-mercaptopurine (6-MP) are the most commonly 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 (slow-acting). Both drugs are dosed at 1.5 to 2.5 mg/kg, with literature supporting the use of higher doses. A Cochrane systematic review that included 13 randomized controlled trials, concluded that azathioprine and 6-mercaptopurine are not effective for inducing remission when a person has Crohn's disease. Azathioprine and 6-MP may be useful for the following indications:
Maintenance therapy with azathioprine or 6-mercaptopurine may lead people with active Crohn's to take less steroid medication. This may lower side effects related to steroid treatments. Fistulizing disease Maintenance of remission after surgery for Crohn's disease A combination of azathioprine and infliximab treatment may be more effective than a single dose of infliximab to induce steroid-free remission for people with active Crohn's disease. Azathioprine treatment may lead to rare but life-threatening side effects. The rare side effects include leukopenia or pancreatitis. There may also be an increased risk of lymphoma that is associated with azathioprine or 6-mercaptopurine treatment. Azathioprine is listed by the United States FDA as a human carcinogen. However, it confers considerably less morbidity and mortality than corticosteroids.
Biologic therapies
Infliximab Infliximab (trade name Remicade, among others) is a mouse-human chimeric antibody that targets tumor necrosis factor alpha (TNFα), a cytokine in the inflammatory response. It is a monoclonal antibody that inhibits the pro-inflammatory cytokine TNFα. It is administered intravenously and dosed per weight starting at 5 mg/kg and increasing according to character of disease. Infliximab has found utility as follows:
Induction and maintenance of remission for people with Crohn's disease Maintenance for fistulizing Crohn's disease Side effects of infliximab, like other immunosuppressants of the TNF class, can be serious and potentially fatal, and infliximab carries an FDA black-box warning on the label. Listed side effects include hypersensitivity and allergic reactions, risk of re-activation of tuberculosis, serum sickness, and risk of multiple sclerosis. Serious side effects also include lymphoma and severe infections.
Adalimumab Adalimumab, like infliximab, is an antibody that targets tumor necrosis factor. It has been shown to reduce the signs and symptoms of, and is approved for treatment of, moderate to severe Crohn's disease in adults who have not responded well to conventional treatments and who have lost response to or are unable to tolerate infliximab. Adalimumab also has a number of serious, potentially fatal, safety concerns characteristic of the anti-TNFα drugs. It, too, has a black-box warning on its FDA label. Listed potential side effects include serious and sometimes fatal blood disorders; serious infections including tuberculosis and infections caused by viruses, fungi, or bacteria; rare reports of lymphoma and solid tissue cancers; rare reports of serious liver injury; and rare reports of demyelinating central nervous system disorders; and rare reports of cardiac failure.
… excerpt ends here. Continue reading the full article.
