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Medications
Below is a list of the wide-range of medications that are currently being used for Crohn's Disease and/or ulcerative colitis. The Food and Drug Administration has never actually approved many widely used IBD medications for specific indications such as induction or maintenance of remission. However, through clinical experience, their efficacy and potential side effects are well-documented.
To view a specific drug category, click on the appropriate link. A physician will recommend the use of medications in various different sequences to control the symptoms of Inflammatory bowel disease, such as diarrhea and cramps. Crohn’s Disease Ulcerative Colitis
5-ASA agents (aminosalicylates)
The first-line medications, particularly helpful for ulcerative colitis, are the 5-ASA agents, which fight inflammation by releasing an anti-inflammatory medication inside the intestine. The first agent, sulfasalazine (Azulfidine), has become a pillar of therapy, particularly for ulcerative colitis, as well as Crohn’s affecting the colon. The other 5-ASA compounds are derived from it, and the active ingredient in these medications are all the same. Aminosalicylates differ in the way they are delivered in the body and where in the digestive system they are released. This category also includes mesalamine (Asacol, Canasa, Pentasa, Rowasa), balsalazide (Colazal) and olsalazine (Dipentum).
Often, after patients have gotten the flare under control and have been taking a 5-ASA compound for a while, they start to feel well and may question the need to take the pills each day. It is very important to know that if these agents are discontinued for six months, at least half of patients with ulcerative colitis will flare. The use in Crohn’s is less dramatic and sustained, but many physicians use it to get a flare of Crohn’s under control and maintain remission. Newer studies have suggested that these compounds may also reduce the risk of colon cancer. The 5-ASA compounds can be very effective with relatively few side effects. Thousands of patients have used them for many years. These compounds can be helpful in mild to moderate disease but have little role in managing severe disease. Common side effects of sulfasalazine are due, in large part, to the sulfa part of the molecule. The reactions can include headaches, nausea, fever, male infertility and rashes. These problems are dose-related, and many patients can get relief of symptoms at doses low enough not to cause side effects. The other part of the molecule (the non-sulfa part) turns out to be the working, or therapeutic part of the molecule, but the sulfa half is important as a chaperone to bring the rest of the compound to the colon where it is needed. If the 5-ASA compound is given alone, it gets absorbed too quickly in the small bowel and doesn’t reach the colon where it is needed. Consequently, a variety of other drugs were developed to deliver the 5-ASA or mesalamine compound to the colon, or where it is needed, without necessitating sulfa. The other compounds on the list of 5-ASA agents have different ways of delivering the 5-ASA portion to the intestines. Pentasa is delivered throughout the small bowel and colon. Asacol is delivered to the last part of the ileum and the colon. Dipentum and Colazal rely on the bacteria in the colon to split 5-ASA from the carrier and release it into the colon to act where it is needed. Another means of delivering the 5-ASA medication, other than taking it by mouth, is to put it directly on the area where the problem is: the colon. If a patient has disease limited to the left side of the colon, or just the rectum, an enema or a suppository for more limited disease can be a very effective way of bringing the disease under control and maintaining it. A medicated enema, Rowasa, that delivers 5-ASA directly to the colon, can reach all the way up the left side of the colon much of the time. A Canasa suppository can deliver 5-ASA up into the rectum. In both cases, the aim is to retain the medication as long as possible by inserting the medication before bedtime and retaining it overnight. Few patients are eager to take enemas or suppositories, but they can be effective and less of an annoyance than taking pills every day.
Immune-modulators act to suppress the excessive inflammation characteristic of IBD. The oldest ones, which have the longest track record of effectiveness, as well as safety, are two compounds, which get broken down by the body into the same active ingredients: Imuran (azathioprine) and Purinethol (6-mercaptopurine). Neoral (cyclosporine) has a role for those with severe ulcerative colitis and occasionally used for a skin manifestation (pyoderma gangrenosum), which can be seen in both ulcerative colitis and Crohn’s disease. Methotrexate, used very widely for rheumatoid arthritis, has been shown to be effective in Crohn’s, but has no role in ulcerative colitis.
Immune-modulators can be highly effective in maintaining a long-term remission in the majority of patients. These two medications, azathioprine (Imuran) and its closely related metabolite or breakdown product, 6-mercaptopurine or 6-MP (Purinethol), are well-tolerated by 90 percent of patients for whom they are prescribed. Some patients taking them will experience a decreased white blood cell count. Consequently, blood counts are monitored throughout the time on the medication. Imuran and Purinethol have been proven safe. These medications are reserved for patients who are unable to discontinue steroids or have more severe disease, which clearly requires a more potent medication and a longer-term strategy to keep the disease under control. The most significant problem these medications present is that they take a considerable period of time to become effective, ranging from two months to more than six months before a clear effect can be seen. The side effects are usually seen in the first few weeks or up to eight weeks, which can happen at any dose. These reactions are unusual, and it is unclear why they occur. About 2 to 3 percent of people may get pancreatitis, less than 1 percent develops an inflammation in the liver, and some may have a rash, fever or nausea - each of which will resolve when the medication is stopped. The other side effects, usually more of a problem at a higher dose, can be a decreased white count and infections, even with a normal white count. Originally used as a treatment for childhood leukemia, immune-modulators are stigmatized as behaving like chemotherapy. Like many medications, if the risks are understood, with careful monitoring, immune-modulators can be safely and effectively used, minimizing any risk. They have been used for a variety of conditions, beginning in the 1950s and widely used in IBD particularly since 1980, so we have a great deal of information concerning their safety and efficacy. A number of myths have developed over the years not verified in the medical literature or in the data generated by numerous studies. If correctly used, most patients gain significant, long-term benefits. A subset of individuals with ulcerative colitis has severe disease that does not respond to the usual medications. For some of these patients hospitalized for refractory, active disease, cyclosporine can be an effective short-term bridge to other medications. Cyclosporine was initially used as a medication to prevent the immune system from rejecting transplanted organs. Studied in patients with very active ulcerative colitis, who failed intravenous steroids, cyclosporine was found to be rapidly beneficial in as many as 80 percent of patients in this group. While it can be effective, it also has numerous side effects that can be serious, though most are reversible. Once a patient responds to cyclosporine in the hospital, they are switched over from the intravenous form to the oral form and are continued, usually not longer than six months, as other medications are added. For the most part, it is useful as a bridge, buying time to allow azathioprine or 6-MP to take effect since they are medications that take time to become active. Studies have not definitively demonstrated a similar benefit for this medication in Crohn’s disease, though it appears effective for some manifestations such as a skin condition called pyoderma gangrenosum. Methotrexate is a medication that can be of use to treat Crohn’s disease, while studies do not support its use in ulcerative colitis. It is widely used in rheumatoid arthritis and has a long track record of safety. The way it works is not entirely clear, but it largely works by suppressing the immune response. Many physicians feel that methotrexate is underutilized in Crohn’s disease. Often used as a third-line agent, after others have failed, methotrexate has been demonstrated to be useful for getting some steroid-dependent patients off steroids. In addition, many can then be maintained in remission on the medication. The side effects are relatively mild, though for some nausea can be a problem. Rarely, more serious side effects can occur, such as scarring of the liver or lungs, but this is very uncommon. The medication is administered by injection, once a week, at the higher doses and can be given orally at lower doses. Methotrexate absolutely cannot be used in pregnancy or if a patient is trying to become pregnant as birth defects are highly likely. In addition, folic acid supplementation should be given along with this medication.
Steroids have been a mainstay of therapy for Crohn’s and ulcerative colitis for decades. Because of their predictable toxicity for those who remain on them for extended periods, great efforts have been made to find alternative therapies to steroids and to educate physicians and patients about the serious side effects associated with their longer-term use.
While there can be a role for steroids, in treating an acute flare for Crohn’s and ulcerative colitis, steroids are not beneficial to maintain remission. Consequently, steroids should never be used for long-term therapy because of their toxicity and their lack of effectiveness. When deciding whether or not to use a medication, the risks and benefits must be assessed and weighed in relation to the particular problem being treated. The issue with steroids is clear on both sides:
Often, particularly when a patient is taking them for the first time, steroids can provide a short-term sense of well-being. But many patients who have been on them for more than a brief period experience side effects. In the very short term, they can be helpful but do not provide a longer-term solution. Physicians worry most about the loss of bone density, cataracts and high blood pressure as well as other less seen medical complications. Patients are more concerned about how it makes them feel (mood swings, sleep disturbance, agitation, depression) and startling changes in their appearance (weight gain, rounded face, skin changes).
Remicade (infliximab) is the first biologic approved for Crohn’s disease, and is an antibody designed to bind to and block the effects of a particular molecule called tumor necrosis factor (TNF), which is central to the inflammation in Crohn’s. Its use is being studied in ulcerative colitis but is currently only approved by the FDA for use in Crohn’s disease.
Remicade is an antibody engineered to block TNF, which is central to the inflammatory response in the body and to Crohn’s in particular. It is given as an intravenous infusion over two hours and can act within one to two weeks, even within days, to bring about significant improvements. When given in Crohn’s initially, it is administered in three doses, the primary dose, a second dose two weeks late, and the third dose four weeks later. Once a response is seen, a maintenance dose can be helpful in keeping the disease under control for many patients. It is not recommended for all patients with Crohn’s but rather for those who are not responding to other therapies, those who are dependent on steroids and those with perianal fistulas. Remicade is currently being studied for use in ulcerative colitis. Remicade is administered as an intravenous infusion over two hours either in a doctor’s office or an infusion center. First, an intravenous line is placed. Some patients require pre-medication. Usually, the medication is infused without any problems, and the patient does not experience anything unusual. Occasionally during an infusion, an allergic reaction can occur. Most infusion reactions can be safely dealt with by administering a mild medication prior to infusion such as Benadryl [diphenhydramine]. Most infusion reactions are mild and can be well-managed without the need to discontinue the medication. With Remicade, as with any medication, the calculation of whether it should be used for a particular patient and in a particular situation depends on the risks and benefits. In general, those medications, which are milder in their benefit, also have milder side effects. A medication with some more significant risks would not be worth trying if a patient has very mild disease that can be managed with a well-tolerated medication that has few side effects. Given its benefits, which can be very effective for some, the downside risk is important to be aware of. As Remicade acts to block an important messenger of inflammation, suppressing the immune system, infection is a concern, though serious infections are not common. An infection, uncommon in the United States, is tuberculosis (TB). Prior to beginning the use of this medication, all patients should have a skin test to determine if they have had a significant exposure to TB in the past because Remicade can cause reactivation of latent or hibernating TB. A primary issue of concern is that the body can react negatively to Remicade by producing its own antibody to it since infliximab is partly a foreign protein. Twenty-five percent of the infliximab antibody is made up of mouse protein, and this may cause an immune reaction against it. A significant problem can be the development of anti-Remicade antibodies, which diminish its benefit, shorten the duration or lessen the extent of response. A number of strategies can reduce the likelihood of this occurring (for example, giving infliximab along with methotrexate). Lastly, infliximab is expensive (as high as several thousand dollars per dose). For Remicade, there are some potentially serious side effects, but, fortunately, the likelihood is low. The risk of infection, as well as a possible risk of lymphoma, is of concern. But they are not sufficiently significant to avoid its use, particularly in those with significantly active disease. Some evidence suggests that Remicade can not only reduce the disease activity but also alter the course of the disease, lessening the requirements for surgery. These benefits need to be weighed by each individual against the potential risks. Furthermore, it is not advisable to start Remicade and then stop for a prolonged period of time, such as many months, as patients can at times develop a delayed reaction, which can prevent its continued use. Consequently, beginning Remicade is not a step taken lightly.
Another category of medications used in IBD is antibiotics, which are used primarily for Crohn’s. The ones used most often include Cipro (ciprofloxicin) and Flagyl (metronidazole). There is little evidence that antibiotics are effective for ulcerative colitis, but they are used widely to treat Crohn’s disease.
When used for Crohn’s, they are indicated for prolonged periods of time, such as two to three months. Studies examining the use of antibiotics in Crohn’s are relatively few, and we need better information to understand which patients can most benefit from them. But some studies have suggested that antibiotics may be more beneficial to Crohn’s colitis than to Crohn’s of the small bowel. In Crohn’s disease that is complicated by an abscess or other infection, antibiotics can play an important role as well. Mild or moderate ulcerative colitis does not benefit from antibiotics. Some patients with severe ulcerative colitis might improve, though this is controversial. Antibiotics can be useful in Crohn’s disease but not in ulcerative colitis. Metronidazole (Flagyl) has long been used for perianal Crohn’s disease, and the combination of ciprofloxicin and metronidazole has gained wider acceptance for intestinal Crohn’s disease, particularly for colonic involvement. One interesting use of antibiotics is the possible benefit immediately after surgery to decrease the risk of recurrence. As mentioned, antibiotics are used for longer periods, often several months at a time. Side effects can include nausea, headaches and loss of appetite. Achilles tendon injury associated with Cipro is uncommon but is worth keeping in mind as it is not the type of side effect one usually thinks of as a complication of an antibiotic. Symptoms include heel pain and swelling.
This section also includes information on the following: Colonoscopy Preparations Currently, there are three types of preparations used to cleanse the bowel prior to a colonoscopy: the phosphasoda prep, the Colyte preparation and the Visicol preparation. The goal is to allow the physician to have a clear view of the colon, clean of fecal matter. Your physician will choose a preparation based on his or her personal experience with previous patients and potential side effects, among other factors.
In addition to the choice of medications to treat IBD, nutrition is an area of research that is relatively neglected, and is of critical importance in Crohn’s and ulcerative colitis. As these are gastrointestinal diseases, it makes sense that nutrition, or what you put into your intestine, ought to have some influence on the disease. However, the optimal diet remains to be determined.
At times, particularly when presenting in childhood or adolescence, the first symptoms of the disease can be poor growth and weight loss. While there are some guidelines and recommendations for managing the nutritional aspects of IBD, more research is needed. Malnutrition and weight loss can be significant problems in IBD. The problem of weight loss may be due to the body’s increased needs because of the inflammation. In addition, in most patients, it is not the case that the intestines are unable to absorb the necessary nutrients. The small intestine is as long as 22 feet in most patients (before surgery), and, in Crohn’s, it is unusual to have such severe inflammation and so much surgery that there is inadequate or insufficient amount of functional small intestine to interfere completely with absorption of nutrition. Nutrition counseling for IBD is often limited to a brief bit of advice. Overzealousness in restriction of diet is not warranted. Advice from a nutritionist, particularly one familiar with Crohn’s and ulcerative colitis, can be more helpful. While no one, specific diet is ideal to help control these diseases , understanding what a healthy diet is and what foods might exacerbate symptoms can be a useful guide. A number of specific supplements and tailored diets have been developed to try to moderate the disease process itself. High-calorie liquid formulas can be used as a source of nutrition, and some patients may need periods of tube feeding.
Several new therapies to treat IBD are currently being studied. The following describe some of the most promising therapies that are now in Phase III trials or under consideration by the FDA. 5-ASA Targeted Antibiotics Biologics
HUMIRA® , or adalimumab, is a drug that blocks the same molecule as Remicade; namely, TNF. TNF is central to the immune system reaction that causes inflammation. HUMIRA® is a fully human protein, and is injected just below the skin by patients or caregivers at home. HUMIRA® is already approved by the FDA as a therapy for rheumatoid arthritis, and is under study in Phase III clinical trials for Crohn’s disease. In 2006, the company expects to seek approval for selling HUMIRA® for Crohn’s disease. Leukine (sargramostim) is approved for oncology and transplant indications to boost the development of white blood cells after chemotherapy. It is also in Phase III trials for Crohn's Disease.
To help determine whether a patient has ulcerative colitis or Crohn’s disease, a physician may order a diagnostic blood test.
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