Maintenance Therapy
The term "maintenance therapy" refers to the various kinds of treatment (usually medical) given to patients to enable them to maintain their health in a disease-free, or limited-disease, state. If you have been diagnosed with Crohn's disease or ulcerative colitis, the first goal of treatment is for you to get better (a stage in the illness known as going into "remission"). The next challenge is to keep you in remission. The treatments used for this second step are referred to as "maintenance therapies."
Why is Maintenance Therapy Needed in IBD?
Both Crohn's disease and ulcerative colitis are chronic inflammatory diseases. Although symptoms may disappear, they tend to recur over time. Many people with IBD respond well to medications when they have a flare-up. Unfortunately, they are at risk for future attacks unless they continue to take certain medications that will keep them in remission. Because these medications are needed over a prolonged period, they must be both effective and safe.
To control inflammation during the acute phase (the initial, active phase of the illness), physicians may prescribe more potent therapies—despite potential side effects—if those therapies will help the patient get better. However, side effects or toxicity from treatment during the maintenance phase are far less acceptable, since IBD can require a lifetime of these medications.
Types of Maintenance Therapies Used in IBD
* 5-ASA Agents
Sulfasalazine (Azulfidine®) and the newer generation of sulfa-free agents (Asacol,® Dipentum,® Pentasa,® Apriso,™ Rowasa,® and Colazal™ are commonly used to prevent flare-ups of IBD. The benefits of these drugs usually depend on the amount of the dose: The larger the dose, the more likely that patients will improve during the acute phase, and the more likely that they will remain in remission. Sulfasalazine's side effects, however, generally become more intolerable as the dose increases. Headaches, nausea, or fatigue are frequently experienced at these higher doses. In men, long-term sulfasalazine treatment may cause abnormal sperm production, leaving some couples unable to conceive. These effects are reversible once the sulfasalazine is discontinued. Patients taking sulfasalazine should also take a daily 1mg dose of folic acid.
Far fewer side effects are seen with the sulfa-free agents, which contain mesalamine (5-ASA), the same active ingredient as sulfasalazine. Side effects—such as headaches, abdominal cramps, and nausea—are uncommon, and generally are not dose-related. However, if you do notice some side effects, you and your doctor may be able to find a slightly lower dose at which the drug is still effective in maintaining remission yet causes no side effects. These agents are much more expensive than generic sulfasalazine, and may require as many as 12 to 16 pills a day to maintain remission. All of these agents may be continued during pregnancy and nursing.
Doses of these medications are generally higher for patients with Crohn's disease than in those with ulcerative colitis. While most of these drugs are available in capsule or pill form, the sulfa-free agents also are available as enemas and suppositories (Rowasa®) for use in patients with inflammation in the rectum or the lower section (left side) of the colon. The usual dose is one enema nightly or two suppositories daily. Maintaining remission by using an enema or suppository often requires continued use of these agents, either alone or in combination with pills, although some patients may find they only need to use the enema a few times each week.
* Antibiotics
Antibiotics are effective as chronic (long-term) therapy in some people with IBD, particularly Crohn's disease patients who have such problems as fistulas (abnormal channels that connect loops of intestine to the skin) or recurrent abscesses (pockets of pus) near their anus. The most commonly prescribed antibiotics are metronidazole (Flagyl®) and ciprofloxacin (Cipro®), although there are many others that may be effective in certain individuals.
Patients whose active disease is successfully treated with antibiotics may be kept on these medications as maintenance therapy if the agents remain effective. Side effects can be particularly troublesome with metronidazole, including tingling of the hands and feet that may persist even after the drug is discontinued. Alcohol intake and exposure to the sun are discouraged, and in most cases these agents are not continued during pregnancy.
* Corticosteroids (Steroids) Steroids (e.g., prednisone, hydrocortisone, Medrol®) are often used in the acute treatment phase when the 5-ASA drugs are not working. Steroids work quickly and effectively in most cases. However, despite their benefit in treating acute illness, steroids are not effective in preventing flare-ups and thus are rarely used as a maintenance medication in either Crohn's disease or ulcerative colitis. Steroids also have many potentially serious side effects—such as elevated blood sugar, high blood pressure, cataracts, osteoporosis (even leading to bone fractures), among others. The risk of adverse effects increases with the duration of the treatment. Thus, steroids should only be used to control the disease. They should then be phased out gradually, while another agent is used to maintain remission.
Strategies to eliminate steroids include increasing the dose of the 5-ASA agents, adding a 5-ASA enema or suppository if the IBD is located in the rectum or distal (lower) colon, or introducing either an antibiotic or one of the newer medications described below. Some patients require surgery if they still cannot effectively reduce or eliminate steroids from their medical regimen.
An exception to steroid elimination rule may be the newer, rapidly metabolized corticosteroids, such as budesonide multiple-release capsule MRC (EntocortREC®). A recent study showed that budesonide MRC is of value as maintenance therapy. Patients on this corticosteroid remained in remission for a markedly longer period than those taking a placebo. The drug was also found to be safe and well tolerated.
* 6-MP and Azathioprine
6-mercaptopurine (6-MP, Purinethol®) and azathioprine (Imuran®) have been increasingly utilized to take IBD patients off steroids, and to keep them off. They are also beneficial in the treatment of some patients with Crohn's disease who have fistulas. Both of these drugs are effective in treating active IBD and in maintaining remission, and are relatively safe. However, patients taking these drugs must be carefully monitored for signs of a decrease in the number of blood cells, or inflammation of the liver or pancreas. Although it was initially feared that patients given these medications could be at increased risk for infections or certain types of cancers, this has not been conclusively demonstrated.
Although these drugs can be expensive, the required daily dose is low. Patients needing these medications to achieve remission will often suffer a relapse of disease when the medications are stopped; thus, many physicians recommend long-term use as maintenance therapy—in some cases even during pregnancy.
* Methotrexate
Methotrexate is recommended in Crohn's disease patients who cannot stop steroid use without a flare of their disease, or in whom other medications have been ineffective. It also may be helpful in improving Crohn's fistulas. This drug has the benefit of once-weekly dosage but must be given as an injection (usually by the patient himself or a family member) for maximum efficacy. Methotrexate is inexpensive, but patients also need to take a daily folic acid pill (1 mg).
If effective, methotrexate should be used on an ongoing basis. Many patients have side effects—most commonly nausea, headache, and fatigue—which may resolve with a lower dose; rarely, liver and lung problems may occur. Careful monitoring by a physician, including periodic blood tests, is essential. Unlike most of the other agents used in IBD, methotrexate is known to cause birth defects. It absolutely must not be taken during pregnancy, or by men or women planning conception.
* Infliximab
Infliximab (Remicade®), is effective in treating moderate to severe active Crohn's disease, ulcerative colitis, and fistulas. Studies have demonstrated that infliximab is not only effective for inducing remission but can be used as a long-term therapy to maintain remission.
Infliximab is given as a single-dose intravenous infusion, and many patients may be able to wait a few months (or longer) before requiring another dose. Patients with fistulas often get three doses over an initial six-week period. Many patients respond quickly, usually within one or two weeks, but it is recommended to wait at least for two infusions to see infliximab's effectiveness.
* Adalimumab
Adalimumab (Humira®) is effective in treating moderate to severe active Crohn's disease. Adalimumab studies have shown to induce remission and it may help keep symptoms from returning with continued therapy. Patients who are intolerant to infliximab may benefit from adalimumab.
Adalimumab is usually injected once every other week, however some patients may need to inject the medication more often in the begining of their treatment. It can be administered at home by the patient or family member once instructed by a healthcare professional. Patient's response time is usually within four weeks.
