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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,® and Rowasa®) 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
The results are just in from the largest
clinical trial of a biologic ever conducted in Crohn's disease patients. This is
infliximab (Remicade™), which is effective in treating active Crohn's disease
and fistulas. Earlier reports had suggested a role as a maintenance therapy as
well and this new study has now demonstrated that infliximab is not only
effective for inducing remission but can be used long-term as therapy to
maintain remission. This biologic approach is effective, safe, and well
tolerated. Furthermore, infliximab treatment provides a rapid and significant
improvement in the quality of life of patients with Crohn's disease, with regard
to general health and vitality, as well as enhancing emotional and social
capabilities. Finally, maintenance infliximab therapy is "steroid sparing,"
allowing more than a third of patients on corticosteroids to discontinue these
drugs while remaining in 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.
The drug works quite quickly, usually within one or two weeks, bringing relief
from the fatigue, fever, and joint pains that may accompany the disease.
Most patients on steroids can move to lower doses and eventually stop them
altogether. Patients are usually encouraged to continue or start drugs such as
6-mercaptopurine, azathioprine, or methotrexate, with the hope that a remission
may be maintained on these agents. Many patients, but not all, require
additional doses of infliximab. Infliximab is very expensive, and its safety in
pregancy is not known. There
is some important information that you must know before you begin treatment with
infliximab (Remicade). Infliximab is not for everyone, and only you and your
doctor can make the decision about whether infliximab therapy is right for you.
Please note the following important information:
Many people with
heart failure should not take infliximab; so prior to treatment you should
discuss any heart condition with your doctor. Tell your doctor right away if you
develop new or worsening symptoms of heart failure (such as shortness of breath
or swelling of your ankles or feet).
There are reports of serious
infections, including tuberculosis (TB) and sepsis. Some of these infections
have been fatal. Tell your doctor if you have had recent or past exposure to
people with TB. Your doctor will evaluate you for TB and perform a skin test. If
you have latent (inactive) TB, your doctor should begin TB treatment before you
start infliximab. Infliximab can lower your ability to fight infections, so if
you are prone to or have a history of infections, or develop any signs of an
infection such as fever, fatigue, cough, or the flu while taking infliximab,
tell your doctor right away. Also tell your doctor if you have lived in a region
where histoplasmosis or coccidioidomycosis is common. Blood disorders have been
reported, some fatal. Tell your doctor if you develop possible signs of blood
disorders such as persistent fever, bruising, bleeding, or paleness while taking
infliximab. Nervous system disorders have also been reported. Tell your doctor
if you have or have had a disease that affects the nervous system, or if you
experience any numbness, weakness, tingling, or visual disturbances while taking
infliximab.
Reports of lymphoma (a type of cancer) in patients on
infliximab and other TNF blockers are rare but occur more often than in the
general population. Tell your doctor if you have or have had cancer.
Serious infusion reactions have been reported with infliximab, including
hives, difficulty breathing, and low blood pressure. Reactions have occurred
during or after infusions. In clinical studies, some people experienced the
following common side effects: respiratory infections (that may include sinus
infections and sore throat), coughing, and stomach pain or mild reactions to
infusion such as rash or itchy skin.
Maintenance Therapy after Surgery
Surgery for ulcerative colitis nearly always results in the complete removal
of the entire colon and rectum. Patients typically undergo one of two
procedures. In the ileal-anal anastomosis, an internal pouch is constructed out
of the end of the small bowel (the ileum), which is attached to the anus. In an
ileostomy, the surgeon creates an opening from the ileum to the skin. Through
this opening, wastes are emptied into a plastic pouch that is attached to the
abdomen with adhesive. Ulcerative colitis cannot recur without a colon or
rectum; thus, there is no need for maintenance medications. However, these
patients may need medication to control diarrhea. In addition, people with an
ileal–anal anastomosis may develop inflammation of the internal pouch
("pouchitis") that requires medication to control.
The aftereffects of surgery for Crohn's disease varies, depending upon the
location of the inflammation. Patients whose Crohn's is limited to the large
intestine (colon and rectum) often do not redevelop the illness (and therefore
don't require maintenance medications) if their entire colon and rectum are
removed, and they are left with an ileostomy. However, if only part of the colon
is removed, then there is a very high likelihood of recurrence of Crohn's
disease. At some point, the disease also may recur in patients who have Crohn's
of the small intestine, because complete removal of the small intestine is not
possible. Patients with Crohn's fistulas often suffer recurrences after surgery,
as well.
Until recently, many Crohn's patients were not placed on maintenance
medications after surgery. However, drugs such as 6-mercaptopurine and
azathioprine, and high doses of the 5-ASA medications and metronidazole have
been shown to delay recurrence of Crohn's disease in some patients. Physicians
may recommend such therapies to patients who are at high risk for recurrent
disease and/or who have already had previous bowel surgeries for Crohn's.
How to Maximize the Chances of Maintaining Remission
Some general guidelines are in order for most patients on maintenance
therapies for IBD. They are:
- The medications won't work if you don't take them.
- If you have Crohn's disease, stop smoking. Smoking can prevent remissions in
Crohn's disease and make it more active. After Crohn's surgery, the illness
recurs sooner, and often more severely, in smokers than in non-smokers.
- Many common over-the-counter and prescription pain relievers have been shown
to cause ulcerations in the intestinal tract, and may prompt a relapse. Unless
you need these products for a serious health reason (such as heart disease or
stroke prevention), you should avoid taking them. Always question your doctor if
the following agents are prescribed: aspirin, including enteric coated
preparations (Ecotrin®); and non-steroidal anti-inflammatory drugs (NSAIDs),
such as ibuprofen (Advil,® Motrin,® Aleve,® Anaprox,® Naprosyn,® Daypro® etc.).
The new "COX-2" inhibitors (Celebrex,® Vioxx®) may also be "off-limits" for IBD
patients.
- Some patients experience flares of their disease after the use of various
antibiotics. Unless an infection is documented by a physician, avoid taking
antibiotics. It is a good idea to contact the physician who is managing your IBD
before taking any new medications to determine if an alternative should be
considered.
Remember, it is often easier to keep IBD under control than to get it under
control. Complying with a demanding treatment schedule isn't always easy, but
the reward—better health—is definitely worth the effort. As we move forward in
our understanding of the causes and genetics of Crohn's disease and ulcerative
colitis, new medications will be developed—both to control active disease and to
maintain remission.
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