Management of Crohn's disease

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, 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:

Azathioprine is a particularly dangerous drug, with the potential to invite a host of life-threatening infections, and is also listed by the FDA as a human carcinogen. However, it confers considerably less morbidity and mortality than corticosteroids.

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:

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 effect 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.

Natalizumab

Natalizumab is an anti-integrin monoclonal antibody that has shown utility as induction and maintenance treatment for moderate to severe Crohn's disease. Natalizumab may be appropriate in patients who do not respond to medications that block tumor necrosis factor-alpha, such as infliximab.

In January 2008, the FDA approved natalizumab for both induction of remission and maintenance of remission for moderate to severe Crohn's disease.

A total of 3 large randomized controlled trials have demonstrated that natalizumab is effective in increasing rates of remission and maintaining symptom-free status in patients with Crohn's disease.

Natalizumab has also been linked to PML (though only when used in combination with interferon beta-1a). The label also recommends monitoring of liver enzymes due to concerns over possible damage or failure.

Also associated with a rare but serious risk of multifocal leukoencephalopathy (brain infection leading to death or severe disability). Therefore, a specific program exists in which prescribers must be enrolled, CD-TOUCH (Crohn's Disease-Tysabri Outreach Unified Commitment to Health) Prescribing Program.

Surgery

Surgery is normally 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). None of these surgeries cure or eliminate Crohn's disease, as the disease eventually comes back in healthy segments of the intestine, although when Crohn's disease recurs after surgery, it usually comes back at the site of the surgery.

Small intestine transplants are becoming less experimental, but are still mainly performed in response to short bowel syndrome due to a high rate of transplant rejection.

Diet and lifestyle

Many diets have been proposed for the management of Crohn's disease, and many do improve symptoms, but none have been proven to cure the disease. The specific carbohydrate diet usually requires adjustments by patients; if a patient finds that certain foods increase or decrease symptoms, they may adjust their diet accordingly. A food diary is recommended to see what positive or negative effects particular foods have. A low residue diet may be used to reduce the volume of stools excreted daily. People with lactose intolerance due to small bowel disease may benefit from avoiding lactose-containing foods. Patients who cannot eat may be given total parenteral nutrition (TPN), a source of vitamins and nutrients.

Fish oil has been found to be effective in reducing the chance of relapse in less severe cases.

Because the terminal ileum is the most common site of involvement and is the site for vitamin B₁₂ absorption, people with Crohn's disease are at risk for B₁₂ deficiency and may need supplementation. In cases with extensive small intestine involvement, the fat-soluble vitamins A, D, E and K may be deficient. Folate deficiency is a risk for patients treated with methotrexate who do not simultaneously receive folate supplementation.

Stress can influence the course of Crohn's disease. Smoking has also been associated with the disease, and smokers with Crohn's are encouraged to explore smoking cessation programs. Smoking can not only make Crohn's disease worse in people who do it, but also increase the risk of recurrence after surgery. If a Crohn's disease patient who undergoes surgery does not quit smoking, the disease is likely to recur more aggressively.

Helminthic therapy

In an experimental idea called helminthic therapy, moderate hookworm infections have been demonstrated to have beneficial effects on hosts suffering from diseases linked to overactive immune systems. This may be explained by the hygiene hypothesis. Hookworm therapy is currently in the trial stage at the University of Nottingham. Due to the unconventional nature of this therapy, it is not widely used.

Alternative medicine

More than half of people with Crohn's disease 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.

Acupuncture

Acupuncture is used to treat inflammatory bowel disease in China, and is being used more frequently in Western society. Evidence has been put forth suggesting that acupuncture can have benefits beyond the placebo effect, improving quality of life, general well-being and a small decrease in blood-bound inflammatory markers. This study however had a very small test set and did not reach the threshold for benefit.

Herbal

Other medications

Non-steroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and naproxen, can cause flares of inflammatory bowel disease in approximately 25% of patients. These flares tend to occur within one week after starting regular use of the NSAID. In contrast, acetaminophen (paracetamol) and aspirin appear to be safe. Celecoxib (Celebrex), a cox-2 inhibitor, also appears to be safe, at least in short-term studies of patients in remission and on medication for their Crohn's disease.

Research

Many clinical trials have been recently completed or are ongoing for new therapies for Crohn's disease. They include the following: