2.2 Q: Are any other drugs used to treat IBD?

There are several different drugs in various stages of development for IBD.

2.2.1 Q Are nicotine patches ever used to treat UC?

Many UC patients have reported that their symptoms began after quitting
smoking. In fact in the vast majority of studies where it has been checked
a significantly lower proportion of UC patients smoke in comparison to
controls. This data is clearly consistent with smoking having a preventive
effect in UC. The mechanism of this is not understood.

In marked contrast a higher proportion of CD patients smoke compared to
controls and continued smoking is a predictor of post surgical recurrence
of CD. This data suggests that smoking may be a co-factor predisposing to
the development of CD. The mechanism of this predisposition is not
understood.

Due to the health risks of smoking, doctors have been skeptical of this
data. Recently more attention has been devoted to understanding the
relationship between smoking and IBD. One question that has stimulated
considerable work has been whether nicotine is responsible for the
apparently protective effect of smoking in UC?

Two relevant articles were recently published in The New England Journal
of Medicine looking at the potential therapeutic benefit of nicotine
patches, normally used to help people stop smoking, to induce remission of
active UC and to maintain remission. The patches were helpful in some
patients in the induction of remission but were not helpful in the
maintenance of remission. Most non smoking patients in the studies
suffered some side effects from the nicotine, including nausea, vomiting,
lightheadedness, headache and sleeplessness. More work needs to be done to
clarify the role of nicotine in therapy of UC. 

2.2.2 Q: What about antibodies against TNF (Tumor Necrosis Factor)?

It is important to note that IBD has features in common with inflammatory
diseases that involve other parts of the body such as rheumatoid arthritis
and psoriasis for example. So therapies that are being developed for these
diseases may also be useful for treating IBD.  There has been considerable
publicity recently given to the new data about the treatment of CD with
antibodies against Tumor Necrosis Factor (TNF).  These antibodies are also
being evaluated in the treatment of rheumatoid arthritis. 

2.2.2.1 Q: What is Tumor Necrosis Factor or TNF?

When the immune system is activated resulting in inflammation many chemical
messengers are released. These chemical messengers are produced by the
cells of the immune system and are called cytokines. These cytokines
interact with other cells encouraging them to become activated and thus
make the inflammation worse. TNF is one of the most important cytokines
involved in this process. The term Tumor Necrosis Factor refers to one of
its actions which led to its discovery.

2.2.2.2 Q: Does TNF serve any useful function?

In the setting of an infection TNF frequently plays an important role in
helping the immune system respond promptly and effectively. However, it is
believed that excessive and inappropriate production of TNF may be an
important contributory factor in the development of several diseases
characterized by inflammation and activation of the immune system such as
multiple sclerosis, rheumatoid arthritis and others.

2.2.2.3 Q: Is TNF important in IBD? just CD? what about UC?

Various strategies have been used to evaluate the importance of TNF in
both CD and ulcerative colitis (UC). Though some data does support a role
it has been difficult to convincingly demonstrate that there is excessive
production of TNF in either disease. The available data does seem to
suggest that TNF may be of more importance in CD than UC. The fact that
the new anti-TNF treatments seem effective in some patients is the best
evidence that TNF is important in the disease process of CD. 

There has been one small study of an anti-TNF antibody in UC and a
preliminary report did not show impressive results.

2.2.2.4 Q: What is this new anti-TNF treatment?

The treatment consists of an antibody which is a protein that neutralizes
the action of TNF. Originally, the antibody was made by a mouse when it
was injected with human TNF. The immune system of the mouse recognized the
foreign nature of the human TNF and made antibodies against it. One of
these mouse antibodies was modified or humanized so that it would be less
likely to provoke an adverse reaction when injected into a human. There
are two antibodies that have been used to treat CD. The first, named cA2,
was developed by the biotechnology company Centecor. The cA2 antibody was
initially used in the treatment of severe infection. More recently it has
been evaluated for the treatment of rheumatoid arthritis. Because of
promising results in the arthritis studies a group of Dutch physicians
gave the antibody to a child with severe CD and there was a dramatic
response.  This encouraged more comprehensive studies of the effectiveness
of the cA2 antibody to treat CD in Europe and the United States. The
second anti-TNF antibody has been developed by the biotechnology company
British Biotechnology and is called CDP571. 

2.2.2.5 Q: How does the anti-TNF treatment work?

The antibodies blocks the action of TNF. The fact that it is so effective
in some patients has raised the question whether it is having some
additional effects on the immune system; however this remains to be
clarified. The most important aspect of its use is that it implies that
TNF does indeed seem to have an important role in the development of
inflammation of CD in a significant percentage of patients. 

2.2.2.6 Q: Are there problems with the treatment?

Like most treatments for IBD it does not seem to work in all patients. In
the recently reported studies most patients who received the treatment had
a beneficial response about half of whom actually went into remission.

In those patients who have a response the effect is temporary, lasting
several months at best. The antibody is given by intravenous infusion and
cannot be given by mouth. It is not clear whether it can be given safely to
the same patient more than once. If indeed it can be given repeatedly it
remains to be seen whether it will continue to have a beneficial effect or
whether resistance will emerge.

The treatment will only be available as part of formal clinical studies for
the next few years. If it continues to have positive results and becomes
available as a standard therapy in the next few years it is likely to be
expensive.

2.2.2.7 Q: What sort of patients are suitable candidates for treatment with
       anti-TNF antibody?

CD patients with active disease despite therapy with steroids; this is a
prerequisite for enrollment in the studies. Those patients who may
particularly be suitable for the anti-TNF therapy are those who cannot
tolerate 6-mercaptopurine or in whom 6-mercaptopurine has not worked or
have just been started on 6-mercaptopurine and a therapeutic effect is not
expected for several months. IMPORTANT: the anti-TNF antibodies are only
available as part of formal studies at present.

2.2.2.8 Q: What are the alternatives available at present?

The best tested and most effective medications at present are 6-MP and
methotrexate. Other medications are also being developed which block the
action of TNF which may be useful in the treatment of IBD in the future.

2.2.3 Q: What about Interleukin-10 (IL-10) therapy for CD?

IL-10 is another cytokine like TNF. Cytokines are chemical messengers
produced by the cells of the immune system that regulate its activity.
Unlike TNF, IL-10 suppresses the immune system and is presently being
studied in the treatment of CD. The results of this study are eagerly
awaited.

2.2.4 Q: What about fish oil for therapy?

There is some evidence that fish oil (attributed to the eicosapentaenoic
acid) has anti-inflammatory properties which may be useful in the treatment
of IBD and rheumatoid arthritis. In addition it may also be helpful in
preventing atherosclerotic cardiovascular disease. Patient acceptance of
fish oil therapy has been poor because of the indigestion and bad breath
associated with therapy. An Italian study last year using coated capsules
containing fish oil showed evidence of benefit in preventing recurrences of
CD with miminal side-effects. However, these capsules are not widely
available at present. In the interim various fish oil preparations
containing eicosapentaenoic acid are available from pharmacies and health
food stores which may be of therapeutic benefit despite the possible
side-effect of increased susceptibility to bleeding. Alternatively it may
be helpful to simply eat more fish in one's diet!

2.3 Q: Can different drugs be used together to treat IBD?

Many patients require treatment with more than one medication to adequately
control their symptoms. Frequently, several different combinations are
tried before the best one is found. Once symptoms are brought under control
then attempts are made to reduce the medications to a minimum.

2.4  Q:  Will I need to keep taking medications permanently?

At this point in time because there is no cure for IBD (except removal of
the colon for patients with UC) it is advisable for many patients to
continue taking medications to keep them in remission. The reason for this,
which is supported by some studies, is that it is much easier to keep a
patient in remission rather than treat a flare of the disease. Similarly,
it is much easier to use sun screen to prevent sunburn rather than try to
treat sunburn after it has happened.

3.1 Q: Drugs aren't working, what can surgery do for my UC?

Drug treatments are ineffective in about 20% of UC patients. These patients
must have their colons removed due to debilitating symptoms. The colon may
also removed because of the threat of cancer. Removal of the colon
permanently cures the UC and usually all related symptoms. Patients having
these surgeries are generally hospitalized for about a week and return to
work in three to six weeks.

There is NO role for resections of only part of the colon in UC even when
the disease is limited in extent as it inevitably recurs in the colonic
remnant.

Once the colon is removed there are several options which may avoid the
need to wear a bag appliance to collect waste.

3.1.1 Q: What's an ileostomy?

The entire colon and rectum are removed and a small opening, about the size
of a quarter, called an ileostomy is made in the lower right corner of the
abdominal wall. The small intestine is then connected to this opening and a
colostomy bag is worn over the opening to collect waste. The patient then
empties the bag about four times a day.

3.1.2 Q: What's a Continent Ileostomy?

Another operation that gained popularity over an ileostomy avoids the use
of a colostomy bag by forming a pouch from the last 15-40 cm of ileum
inside the wall of the lower abdomen. A nipple valve in the abdominal wall
allows the patient to empty the pouch by inserting a catheter through the
ileostomy. Initially, the pouch must be emptied frequently, eight to ten
times daily. The pouch stretches and, after several months it will only
have to be emptied four to five times a day. This operation used to be
performed in two separate steps and the patient would have to wear a
colostomy bag for several months before the pouch could be attached. The
operation is now generally performed in one step, though it may be
performed as two steps if the patient is severely ill at the time of
surgery.

This procedure is generally not performed because it has many of the
possible complications and none of the benefits of the Ileoanal
Anastomosis, described below.

3.1.3 Q: What's an Ileoanal Anastomosis, or Ileoanal Pull-Through?

Since UC inflames only the innermost layer of the colon, the rectum can be
stripped of this layer and attached to the ileum after the colon is
removed. Early attempts to perform this surgery were frustrating as
patients predictably suffered from incapacitating diarrhea. The operation
was modified in 1980, adding an S or J shaped pouch just above the rectum
and patients achieved continence. The patient can then pass stools
normally, though bowel movements are more frequent and watery than in an
otherwise healthy individual without IBD.  Like the Kock pouch, eight to
ten bowel movements a day are typical immediately after the surgery. The
pouch continues to stretch for several years and eventually it's only
necessary to have four or five bowel movements a day.  In rare cases
(around 5% when the surgery is performed by an appropriately trained
surgeon) when other complications, such as infection occur, the pouch may
need to be converted to an ileostomy.

3.1.4 Q: What can go wrong with these surgeries?

The most common complication of these operations is inflammation of the
pouch, called pouchitis.  Symptoms include pain, bloating, and diarrhea.
Most patients can control this by irrigating the pouch with saline solution
and taking antibiotics. In a few cases, a diagnosis of CD is confirmed in
patients thought originally to be suffering from UC.

Problems with the nipple valve in a continent ileostomy can cause leakage
of stool and an inability to insert the catheter.  About 10% of patients
require a second operation to repair the nipple valve.

Remember that these have the same risks as any surgery, but that's outside
the scope of this FAQ.

3.2 Q: Are there surgical treatments for Crohn's?

Unlike in UC, there is no surgical cure for CD.

Physicians use the phrases "minimalist surgery" and "surgery avoidance"
when discussing surgical options for CD. This is because new Crohn's
lesions can appear after previously diseased areas have been removed and
even diseased tissue may be functionally useful. Many surgeons also feel
that "surgery in Crohn's patients just leads to more surgery".

Surgery for CD is usually a resection of the small intestines.

3.2.1 Q: What's a resection?

Severely affected portions of the intestine are removed and the healthy
ends are sewn together. This in no way prevents inflammation from recurring
later and is generally performed only when the inflammation is unable to be
controlled by medical therapy.

3.2.2 Q: After surgery for CD can anything be done to prevent it recurring
again?

Smoking is associated with recurrent disease following surgery in CD
patients. Clearly, CD patients must be strongly encouraged to stop smoking.

There is some evidence that 5-ASA drugs (especially Pentasa for small bowel
disease) may be useful in preventing disease recurrence after surgery. Some
experts use 6-MP following surgery in patients with a high risk of
recurrence and there is a trial in progress to see if it works in this
setting. There is also some limited evidence that metronidazole may be
helpful in preventing disease recurrence following surgery. Fish oil may
also be a relatively safe option though it is not of proven benefit.

4.1 Q: What role does diet play in IBD?

Most patients find that certain foods are tolerated less well than others
when symptoms are active, but there is no evidence that these foods
directly affect the inflammation. The most common offenders are milk
products (see the section on lactose intolerance below), spicy
foods, fats, and sugars. In general, a bland low fiber diet avoiding
fruits, vegetables, nuts, and whole grains is preferable when the disease
is active. A high fiber diet is to be recommended when symptoms aren't
present.

Due to reduced appetite, malabsorption of nutrients, and increased
nutritional needs, it's important to make sure you follow a proper diet. 
Since the small intestine is where the body absorbs nutrients from food,
CD patients may have problems absorbing these nutrients.  If more than two
or three feet are either diseased or surgically removed,malabsorption,
especially of fats, the minerals calcium and magnesium, and the fat
soluble vitamins A,E, and D, can be a problem. Resection of at least two
feet may also increase absorption of oxalate, which reacts with calcium to
form kidney stones. A low oxalate and low fat diet will help prevent
kidney stones. Spinach, cocoa beans, rhubarb, beets, instant coffee, diet
sodas and tea are all high in oxalate. If only the terminal ileum, the
last two to three feet of the small intestine, is diseased or resected,
absorption will be normal except for vitamin B-12 which can be
supplemented by monthly injections. Iron supplements are helpful in
treating the anemia and patients should drink plenty of fluids to replace
those lost from diarrhea. 

4.1.1 Q: What is an elemental or astronaut diet?

Astronaut diets (for example Ensure, Sustacal and Peptamen) are liquids
meeting all nutritional needs and are almost completely absorbed in the
upper intestinal tract. Because they don't require much digestive effort by
diseased bowel they often seem to be better tolerated than regular food by
patients with active and/or severe disease. Elemental diets (for example
Vivonex) consist mainly of pure amino acids (the building blocks that make
up proteins) and are even easier to digest. There is some evidence that
elemental diets may be helpful therapeutically in CD. However, these diets
are expensive and patients find it difficult to comply with them on a long
term basis so they have not evolved into a practical treatment.

In contrast there is no evidence that elemental diets are of benefit in UC.

4.1.2 Q: What is total parenteral nutrition?

Total parenteral nutrition (TPN), or hyperalimention, delivers a
concentrated solution of nutrients intravenously. This is used in very
active disease either giving it time to subside, or to nourish the patient
before surgery.

People with Crohn's Disease generally benefit more than those with UC
because CD usually affects the small intestine, which is where nutrients
are absorbed. TPN may, however, occasionally be warranted in critically ill
people with UC.


4.1.3 Q: What is lactose intolerance?

It's commonly estimated that about 30% of the world's adult population
suffers from lactose intolerance, though this may be even higher in
patients with IBD. A much higher than normal fraction of Asians suffer from
lactose intolerance.

Lactose is a sugar found in milk, milk products, and foods made with milk.
The enzyme lactase, normally produced in our intestines, breaks down
lactose during digestion. Lactose intolerant people don't produce enough
lactase and therefore cannot digest lactose.

Symptoms of lactose intolerance include a bloated feeling, abdominal pain,
flatulence, and diarrhea shortly after consuming milk or milk products. 
Sound familiar?  It's not something that you want to subject yourself to
in addition to the symptoms of Crohn's or UC. A simple laboratory test can
determine whether one is lactose intolerant or not.  The severity of
symptoms is highly individual and most people do not need to eliminate
lactose from their diet entirely. 

4.1.3.1 Q: So what can I do about lactose intolerance?

1.  Reduce or Remove milk and milk containing foods from your diet. These
include milk chocolate, butter, cheeses, ice cream and lactose--it's an
ingredient by itself in some foods.  Check the label!

2.  Eat foods containing lactose with meals containing protein and fat, not
alone.

3.  Use a lactose reducing product available over the counter at most
pharmacies (Dairy Ease or Lactaid). These contain lactase and are either
consumed with lactose rich food or added to it before eating.

Some dairy products have reduced lactose content. These include yogurt and
Lactaid Milk.

4.  Fermented milk products, such as aged cheeses, contain less lactose and
are usually better tolerated.  Cottage and ricotta cheese are OK, cheddar
has about the least. Buttermilk contains as much lactose as milk.

5.  A calcium supplement may be needed if dairy products are reduced or
eliminated from your diet.

5.1 Q: What part does stress play in IBD?

Emotional stress plays a large part in the health of some patients and is
often cited as the trigger of a relapse, though there is no clear cause and
effect relationship proven. It may be more likely be that stress is one
result of a flare-up rather than being a factor contributing to one.
Treatment of IBD sometimes may usefully include the teaching of stress
reduction techniques such as meditation.

This is a controversial subject with somewhat "political" overtones. Many
patients resent the assumption of family and friends and even some doctors
that stress is a cause of their illness, when in fact it is just an
exacerbating factor (as is the case with other illnesses, as well). Many
people need reassurance that all this is not their fault or "all in their
head". It's been proven that stress does NOT cause IBD, although with IBD
as with any illness stress can exacerbate symptoms.

Because of the nature of these illnesses and the unpleasant symptoms that
result patients frequently feel very uncomfortable about discussing them
even with close friends and family. Denial may be a factor that inhibits
patients from getting appropriate evaluation and therapy.

Many patients find patient support groups to be extremely helpful in
addressing these issues and enabling patients to constructively and
positively learn how to live with these chronic illnesses. Many patients
not comfortable with group discussions  have found it particularly helpful
to consult with a psychologist experienced in the evaluation of patients
with IBD.

5.2 Q: Can anything else cause a flare up?

Significant anecdotal evidence suggests that flares of IBD often occur
after increased use of non-steroidal anti-inflammatory drugs (NSAID's),
such as aspirin and ibuprofen. Accordingly, patients should be very careful
about taking these medications and be aware that they may cause a flare of
their disease. In fact, some physicians who are very experienced in
managing IBD feel these drugs should rarely if ever be used by IBD
patients.

6.1 Q: How can I make the most of my consultations with my physician?

For your physician to treat you most effectively it is vital that you
adequately describe your symptoms. Many patients are reticent about
describing urgency and episodes of incontinence for example which may be
readily treated with local topical therapy. If despite the best efforts of
your physician you are not doing well either having continued symptoms or
requiring continued high dose steroids then it may be appropriate to
consider asking for a second opinion. This is best done in conjunction with
your regular physician.



======================================================================

COPYRIGHT NOTICE

Copyright 1997 by Kevin Horgan, M.D., Christopher Holmes and Michael 
Bloom.   All rights reserved. 

This document, or any derivative works thereof, may not be sold or
redistributed for profit in any way without express (not email) written
permission of the authors.  This includes, but is not limited to,
translations into foreign languages, mass archival as on a CD_ROM and
inclusion in commercially published compilations (books). 

You are free to copy this list for personal use, or to make it available
for redistribution in its electronic format, provided that: 

(1) it remains wholly unedited and unmodified, 

(2) no fee or compensation is charged for copies of or access to this
    list, and

(3) this copyright notice and the following disclaimer remain attached. 



DISCLAIMER:
==========
This FAQ is provided by the authors "as is", and any express or implied
warranties, including, but not limited to, the implied warranties of
merchantability and fitness for a particular purpose are disclaimed.  In
absolutely no event shall the authors be liable for any direct, indirect,
incidental, special, exemplary, or consequential damages (including, but
not limited to, procurement of substitute goods or services; loss of
use, data, or profits; or business interruption) however caused and on
any theory of liability, whether in contract, strict liability, or tort
(including negligence or otherwise) arising in any way out of the use of
the information herein contained, even if advised of the possibility of
such damage.  

In other words, this document is in no way intended to be a substitute
for medical care; the information contained herein is presented by the 
authors purely for informational purposes only.  In no way are any of 
the materials presented here meant to be a substitute for professional 
medical care or attention by a qualified practitioner, nor should 
they be inferred as such.  ALWAYS check with your doctor if you have 
any questions or concerns about your condition, or before starting a 
new course of treatment or otherwise making any decisions about treatment. 


______________________________________________________________________________
Kevin Horgan, MD
khorgan@ucla.edu
310-206-3580 phone
310-206-9049 fax