Crohn's disease is an inflammatory bowel disease (IBD) in which parts of the digestive system become inflamed. Patients with Crohn's disease may be affected anywhere in the digestive system, from the mouth all the way down to the anus and rectum. The exact cause of Crohn's is unknown. Current medical opinion is that the body's immune system attacks the digestive tract and causes symptoms both within the digestive tract and in other parts of the body. Fortunately, a variety of medications are available to treat Crohn's disease and its accompanying symptoms.
5-Aminosalicylic Acid Agents
Mesalamine (sold under the brand names Pentasa and Asacol) and sulfasalazine (brand name Azulfidine) are called 5-ASA agents because they are derived from a molecule called 5-aminosalicylic acid. These are often the first medications patients are put on when they are diagnosed with Crohn's disease of the colon or ileocolon (the transition area between the small and large intestines).
Although sulfasalazine and mesalamine are often used both to treat mild-to-moderate active Crohn's disease and to keep patients in remission, studies have not clearly shown that they are actually effective at doing either of these things. The frequency with which physicians prescribe these medications likely relates to the fact that of all the medicines used for Crohn's, the 5-ASA agents have side effects that are relatively minor. Side effects of sulfasalazine include nausea, fever, headache and male infertility. These side effects are related to the the dose the patient is on--the higher the dose, the more likely the patient is to experience these effects. Side effects of mesalamine are generally more mild and include nausea, headache and abdominal pain. Both mesalamine and sulfasalazine may cause diarrhea at the beginning of treatment. This side effect generally disappears within the first few weeks on the medications.
Antibiotics
If patients with Crohn's disease either do not tolerate the 5-ASA medications, or simply do not seem to be improving while on them, many physicians use certain antibiotics as the next step in treatment. The goal is to improve symptoms without having to use corticosteroids (prednisone), because steroids have many severe side effects. Commonly used antibiotics include metronidazole (taken by mouth, at doses of 10 mg per kilogram of body weight per day) or ciprofloxacin (a dose of 500 mg taken twice daily). Antibiotics are commonly administered for six to 12 weeks, although there is little objective evidence of their effectiveness. It is thought that perhaps the antibiotics work by decreasing the inflammation in the intestine, by treating tiny tears in the intestine, or by changing the balance of bacteria in the intestine.
Corticosteroids
Prednisone is the "workhorse" of Crohn's disease treatment. It is used if patients fail to improve by taking 5-ASA agents or antibiotics. It is also used to treat patients who had been in remission (their Crohn's symptoms had been minimized or eliminated) and who begin to experience symptoms again (a "flare" of the disease).
The advantage of using prednisone (or a related steroid called budesonide) is that it often results in dramatic improvement of symptoms in most patients. The disadvantage is that prednisone does not treat the actual disease--it merely suppresses the symptoms. Another major drawback to using prednisone is its long list of uncomfortable and potentially serious side effects. Side effects range from the relatively mild (easy bruising, headaches) to the more severe (mood swings, muscle weakness, bone fractures). Potentially life-threatening side effects include congestive heart failure, diabetes and risk of infections. Finally, in children, one effect of long-term prednisone use is growth failure.
Immunomodulating Drugs
Azathioprine, mercaptopurine, and methotrexate are known as immunomodulating drugs because they modulate (affect) the immune system. In Crohn's disease patients who have not improved after treatment with steroids, or in patients who need recurring courses of long-term steroids in order to control their symptoms, immunomodulators are the next step in treatment. Unlike some of the other medications used in Crohn's treatment, studies have shown that these types of drugs do result in signficant improvement in patients. In patients who have been on steroids, using one of these drugs allows the majority of patients to either eliminate or greatly decrease their need for steroids. Also, once remission has been achieved (usually within several months of beginning therapy), the use of immunomodulators has been found to greatly decrease the risk of future relapses. The disadvantage of these drugs is that they suppress the immune system, putting patients at greater risk for infection and making them less able to fight infections; chronic immunosuppression also increases the risk of certain types of cancers.
Anti-TNF Drugs
Some patients with moderate-to-severe Crohn's disease will not respond even to the immunomodulating drugs. In this case, use of the medications infliximab (Remicade), adalimumab (Humira), or certolizumab (Cimzia) may be helpful. These drugs are called anti-TNF drugs because they are work by opposing a substance called Tumor Necrosis Factor (TNF). They are given via an intravenous (IV) infusion every two to eight weeks, depending on the drug. As with the immunomodulating drugs, a major concern is the increased risk of serious infections due to the patient's immune system being suppressed by the anti-TNF drugs.
Symptomatic Medications
Crohn's disease patients often suffer from diarrhea, and though active Crohn's disease is itself a cause of the diarrhea, other causes may be involved as well. For instance, patients with disease in the end of the small intestine (called the terminal ileum) may have difficulties absorbing certain substances called bile salts. These patients will often have loose, watery stools because of the decreased bile salt absorption and could benefit from medications such as cholestyramine or colestipol; these medicines help bind the bile salts and can improve the diarrhea. Other patients may find their diarrhea symptoms improve by taking an over-the-counter antidiarrheal such as loperamide (Immodium A-D). In such cases, treating these other causes may result in enough improvement that steroids and immunomodulating drugs can be avoided.
References
- MicroMedex "Azathioprine"
- "UpToDate"; Denise Basow; 2010
- "Current Medical Diagnosis and Treatment"; Stephen J. McPhee and Maxine Papadakis; 2010
