Authors: Rita Baron-Faust,Jill Buyon
The Autoimmune Connection: Essential Information for Women on Diagnosis, Treatment, and Getting On With Your Life (32 page)
The treatment for your Crohn’s depends on how much of the bowel is involved and how severe the disease is (for example, if you have fistulas) and any other complications you may have. The goal is to control inflammation; relieve symptoms like abdominal pain, diarrhea, and rectal bleeding; and correct any nutritional deficiencies. Treatment may include medications, surgery, nutritional supplements, or a combination.
You can experience long periods of remission—sometimes years without any symptoms—with proper treatment. But there’s no cure for Crohn’s, and it can recur periodically. Unfortunately, there’s no way to predict when this may happen. Although it can be controlled, Crohn’s is a chronic disease, and you’ll need regular medical visits, periodic diagnostic tests in the event of a recurrence, and sometimes a change in your medication.
Sulfasalazine (Azulfidine)
has been the most common drug for treating Crohn’s. It contains a sulfa preparation (
sulfapyridine
) that has antibiotic properties. Sulfasalazine also contains
mesalamine
, an aspirin-like substance that helps control inflammation and is used to treat mild to moderate Crohn’s. Sulfasalazine is also helpful in treating flares of Crohn’s colitis and ileitis. Side effects include nausea, vomiting, heartburn, diarrhea, appetite loss, and headache. If you’ve had allergic reactions to other sulfa drugs, you may have a rash in reaction to sulfasalazine; in this case, the drug may be stopped. It can also interfere with the absorption of digoxin and folic acid. Your doctor will continue the medication until symptoms go away. Once you’re in remission, you’ll be put on a maintenance dose. Sulfasalazine can safely be used during pregnancy (see
page 259
).
Aminosalicylic acid (5-ASA)
agents are aspirin-like drugs that also contain mesalamine, and have largely replaced sulfasalazine. The 5-ASA agents include
balsalazide
(
Colazal
and a generic),
olsalazine sodium (Dipentum)
, and
mesalamine (Pentasa, Asacol, Delzicol, Apriso)
.
These are coated capsules with pure 5-ASA that are delivered either to the small bowel or to the terminal ileum into the early part of the colon; or, if it’s
the distal colon, Asacol is delivered to that area. Pentasa is delivered to the small bowel. They can also be given orally.
Immunosuppressants
are used to treat moderate to severe Crohn’s disease. The most commonly prescribed are
6-mercaptopurine (6-MP, Purinethol)
,
methotrexate
, and
azathioprine (Imuran)
, a chemical cousin to 6-MP. Immunosuppressive agents work by blocking the immune reaction that contributes to inflammation. It may take three to four months for 6-MP to show benefits.
These drugs can cause fever, bone marrow suppression, and, in some cases, pancreatitis. While taking these drugs you’ll need careful monitoring of your blood counts and liver function tests. Immunosuppressant drugs may also cause side effects like nausea, vomiting, and diarrhea, and may lower your resistance to infection.
Corticosteroids (glucocorticoids)
are also used to treat moderate to severe disease, as well as severe or fulminant Crohn’s. Among the most commonly prescribed are
prednisone (Deltasone, Orasone)
and
prednisolone (Prelone)
.
Budesonide (Entocort EC)
is a steroid that’s released in the intestine, where it works locally and topically to decrease inflammation, avoiding many of the side effects of systemic corticosteroids. Budesonide capsules are approved for mild to moderate Crohn’s disease involving certain sections of the small and large intestines. It is also used along with anti-diarrheal agents (see
page 254
).
Clinical trials among people with active Crohn’s have found that the drug significantly improves symptoms. The most common side effects include headache, respiratory infection, and nausea. In comparison with prednisolone, fewer patients on budesonide experienced facial swelling and acne. Although your doctor may try to avoid the use of corticosteroids because of side effects (like a fatty liver) and the risk of osteoporosis, these drugs may enhance the effects of immunosuppressive drugs. When used in combination with immunosuppressants, the dose of steroids can be lowered. While steroids are very effective in bringing about a remission, nearly half of women may become dependent on them and need to be tapered off the drug. (For more details on corticosteroids, see
pages 42
to
43
.)
Biologic therapies
for IBD and Crohn’s target specific enzymes and proteins that are elevated, very low, or defective.
Infliximab (Remicade)
blocks the inflammatory cytokine
tumor necrosis fac
tor alpha (TNF
α
)
, which damages tissue in Crohn’s, rheumatoid arthritis, and other autoimmune diseases. It’s a monoclonal antibody that targets the
TNF molecule, binds to it, and removes it from the bloodstream before it reaches the intestines, preventing further inflammation. It’s also approved for ulcerative colitis.
8
Remicade is given as an intravenous drip (it takes about two hours) every eight weeks. It’s used to treat moderate to severe Crohn’s and for people who don’t respond to sulfasalazine, 5-ASA agents, or immunosuppressive agents. It is also approved to treat people with fistulas and to induce and maintain remissions of Crohn’s. Side effects include an increased risk of serious infection, and a lupus-like syndrome. It is used in combination with 6-MP, azathioprine, or a 5-ASA compound. Remicade should be avoided during pregnancy (see
page 259
).
Two other TNF
α
blockers are also approved for treating moderate to severe Crohn’s disease—
Adalimumab (Humira)
and
certolizumab pegol (Cimzia)
. Adalimumab is given by self-injection every other week. The first three injected doses of certolizumab are given every two weeks and after that once a month. Infliximab and adalimumab appear to be similarly effective at maintaining remission in Crohn’s.
9
According to the CCFA, approximately 60% of people with IBD respond to anti-TNF
α
therapies and, among these patients, about 35% will be in remission at the end of one year.
TNF
α
drugs produce mucosal healing, do away with inflammation, and change the natural history of the disease. One of the big problems of Crohn’s is that patients get scarring, stenosis, obstructions, and fistulas, and these drugs shut all that down.
A number of new treatments have been approved by the FDA. These include the intravenous drug
vedolizumab (Entyvio)
,
10
approved for adults with moderate to severe Crohn’s and ulcerative colitis who haven’t responded well to corticosteroids, immunomodulators, or TNF blockers. Vedolizumab is among a new class of drugs called
integrin receptor antagonists
. These drugs block a protein that sits on circulating inflammatory cells from interacting with a protein on the inner surface of blood vessels, preventing them from migrating into the GI tract.
The first dose of vedolizumab is followed by infusions at two, four, and six weeks, then every two months after that. The infusion takes around a half hour. The most common side effects include headaches, joint pain, nausea, and fever, as well as serious infections and liver toxicity. It’s uncertain whether
the drug, like another type of integrin receptor antagonist, causes a rare and often infection of the nervous system called progressive multifocal leukoencephalopathy (PML), a disease that affects the myelin sheathe around nerve cells, so patients must be monitored.
11
Natalizumab (Tysabri)
is an
alpha 4 integrin inhibitor.
It interferes with a cell adhesion molecule (which acts as kind of molecular glue) so white blood cells can’t stick to receptors in inflamed tissues. The drug, also used to treat multiple sclerosis, is approved for adults with active moderate Crohn’s disease who haven’t responded to TNF blockers or other drugs.
12
Natalizumab is given as an intravenous infusion (it takes around an hour to receive a full dose) and is usually administered every four weeks. It has some of the same side effects as vedolizumab and can also lead to PML, and patients being treated for Crohn’s or MS with the drug must be monitored for neurological symptoms, such as vision loss, impaired speech, weakness or paralysis, and cognitive deterioration. PML is diagnosed by testing for a virus called the JC virus.
Antidiarrheal agents
can be used to relieve the cramps and diarrhea of Crohn’s. These include
diphenoxylate (Lomotil)
and
loperamide (Imodium)
. In severe cases you may become dehydrated, so you’ll need plenty of fluids (such as Gatorade) to replenish electrolytes. Budesonide is also used to relieve symptoms of diarrhea.
A prescription “medical food,”
EnteraGam
, is designed for people whose diarrhea prevents them from digesting, absorbing, and metabolizing food.
13
The special proteins in this product (
serum derived bovine immunoglobulin/protein isolate
) remain in the intestine and are not absorbed whole, as are proteins from regular food. It can also help manage diarrhea.
Cholestyramine (Questran)
is a cholesterol-lowering agent that can be helpful in controlling diarrhea. Patients with IBD affecting the end portion of the ileum (or who have had surgery) may not be absorbing bile salts in the area, which causes the colon to secrete fluid and electrolytes, leading to watery diarrhea.
Antibiotics
are used to treat bacterial overgrowth (and resulting inflammation) in the small intestine caused by fistulas, strictures, or prior surgery. Commonly prescribed antibiotics include
ampicillin
,
sulfonamide
,
cephalosporin
,
tetracycline
,
ciprofloxacin (Cipro)
, and
metronidazole (Flagyl)
. These are also used to treat abscesses and perianal fistulous disease.
Nutritional supplements
, either oral supplements or injections, may be recommended in people who have deficiencies of vitamin B
12
or vitamins D, A, or K. The anemia caused by malabsorption of vitamin B
12
in the ileum is treated by monthly B
12
injections.
In severe disease with considerable weight loss, special high-calorie liquid products are sometimes used to boost nutrition. A small number of patients with severely inflamed intestines, or who cannot absorb enough nutrition from food, may need temporary intravenous feeding.
Women with Crohn’s also need to watch their diet, avoiding foods that irritate the bowel, such as spicy foods or high-fiber foods.
The following classifications have been developed by the American College of Gastroenterology (ACG) and are used to help determine or adjust treatment. Your doctor may also use the Crohn’s Disease Activity Index (CDAI) to monitor your condition.
Mild to moderate disease:
You are able to eat normally without pain, abdominal tenderness, painful intestinal masses (or obstruction), fever, or dehydration.
Moderate to severe disease:
You have failed treatments for mild to moderate disease, or you have prominent symptoms like fever, weight loss (more than 10 percent of your body weight), abdominal pain and tenderness, periodic nausea or vomiting (without bowel obstructions), or anemia.
Severe (or fulminant) disease:
Symptoms persist despite treatment with corticosteroids or other immunosuppressant drugs, or you present to your doctor with high fever, persistent vomiting, abdominal tenderness, severe weight loss, evidence of an abscess or obstruction.
Remission:
This is defined as the absence of symptoms or signs of inflammation. It includes women who have undergone acute treatment or surgery.
If symptoms don’t respond to drugs, or there are repeated blockages or bleeding in the intestine, surgery may be the next step. While surgery to remove a damaged section of intestine can help Crohn’s disease, it doesn’t cure it.
Unfortunately, inflammation tends to recur right next to the resected area of intestine.
In severe cases where Crohn’s has damaged the large intestine, some women may need to have their entire colon removed. The procedure, called
colectomy
, brings the end of the ileum to the surface of the lower right side of the abdomen, with an opening the size of a quarter (stoma), to allow waste to exit into an external pouch (which is emptied as needed). In some cases, women can avoid a colectomy, having only the diseased section of intestine removed and the two ends reconnected (
anastomosis
), with no stoma or bag needed. However, this procedure has a higher risk of disease recurrence. (Smoking also increases the risk of recurrence after surgery.)
Mesalamine, 6-MP,
and
Imuran
are all being tested to see whether they can prevent recurrences after surgery. If your Crohn’s is severe, you need to discuss the pros and cons of surgery with your physician.
Small bowel transplants may also be helpful. According to the CCFA, transplants of a small section of healthy intestine from a donor can reverse intestinal failure. As with any transplant, lifelong immunosuppressant treatment is needed.
New biologic therapies being researched for Crohn’s including other TNF
α
inhibitors, additional drugs that target alpha 4 integrin, and agents to suppress inflammatory cytokines such as interleukin-12 (IL-12)
semapimod
14
and interferon gamma (
fontolizumab
).
15
IL-10 is a cytokine that suppresses (rather than produces) inflammation and studies are underway into a synthetic form of IL-10 for treating Crohn’s disease.
Drugs approved for other autoimmune diseases are also being tested in Crohn’s such as the
Janus kinase (JAK)
inhibitor
tofacitinib (Xeljanz)
16
and the IL-6 inhibitor
tocilizumab (Actemra)
both used to treat RA.
17
The psoriasis drug
ustekinumab (Stelara)
, which targets IL-12, may help people with Crohn’s resistant to TNF-blockers.
18
One experimental therapy is designed to produce “oral tolerance”—using an oral agent to induce the immune system to tolerate specific antigens—with an extract called
Alequel
, derived from a mixture of colon-extracted proteins from the patient’s own gut. The therapy could be individually tailored and it appears to be safe.
19
Antibiotics are now used to treat the bacterial infections that often accompany Crohn’s disease but some research suggests that they might also be useful as a primary treatment for active Crohn’s and for fistulas.
Thalidomide (Thalomide)
has been used with some success in Crohn’s and is being tested in ulcerative colitis (see
page 81
).
20
And the use of stem cell transplants to treat severe Crohn’s is also being investigated.
21
Janine’s story continues:
I always had worse symptoms around my periods . . . I would have increased bowel activity, going to the bathroom a lot more during that time of the month. I went on birth control pills for other reasons—I actually was having ovarian cysts and they were concerned about that. But after I started on them I didn’t fluctuate, even on my off week. My doctor was kind of reluctant to put me on the pill, so he put me on a low-dose pill because he thought maybe the hormones would cause my Crohn’s to flare. But I’ve never had a problem with it. The only non-GI symptoms my doctor ever asks about are joint pain. But we never discussed my susceptibility to other autoimmune diseases. And I’m not sure if it’s just because he’s a gastroenterologist and he’s not thinking about it because he’s only interested in my Crohn’s. But aside from arthritis concerns, they don’t monitor me for thyroid or anything else.
