Crohn's Disease Drug Treatment and Surgery
Patients and physicians often agree that the drug treatment of Crohn's
disease is disappointing at best. The most useful drug, prednisone, has
long-term consequences. Too many patients have acute crises such as perforation
and obstruction of the small bowel and require surgery. Relapses after surgery
are common. The usual goals of therapy are to correct nutritional deficiencies,
to control inflammation and to relieve abdominal pain, diarrhea and rectal
The most commonly used drugs are:
- Sulfasalazine often lessens the inflammation, especially in the
colon. Side effects such as nausea, vomiting, weight loss, heartburn,
diarrhea, and headache occur in a small percentage of cases.
- Mesalamine or 5-ASA agents (Asacol, Pentasa, Rowasa, Dipentum).
- Steroids - prednisone
The mechanisms of action of immunosuppressant are multiple and include preventing/inhibiting cell
activation, cytokine production, cell differentiation, and/or proliferation. Imunosuppressants can also
work by stimulating the expression of immunosuppressive molecules and/or cells.
All hypersensitivity diseases can be treated by immunosuppressant drugs, but
because these drugs have host of negative consequences, trails of their use in
immune-mediated diseases has be slow and cautious. In organ transplant programs,
however, immunosupression is essential to success and many drug combinations
have been tried.
Lifelong prednisone has been the mainstay of transplant programs. The protocols used in most transplant centers
involve the use of multiple drugs, each directed at different mechanisms in the
T-cell activation cascade and each with distinct side effects. Cyclosporine,
azathioprine, corticosteroids, tacrolimus, and mycophenolate mofetil are used.
Prednisone is arguably the best drug for many chronic inflammatory disease, but it may not be prescribed because it has
long-term side effects, which scare both physicians and patients. Steroids are
useful in reducing the whole-body disease with control or elimination of
symptoms such as fever, anemia, weight loss, neuropathy and vasculitis (blood
vessel inflammation). Prednisone is often the best choice for initial therapy of
acute inflammatory diseases. If the use of this drug is short term, then it is
an excellent, inexpensive and well-tolerated drug. A Cochrane review
concluded that:” The use of conventional systemic corticosteroids in patients
with clinically quiescent Crohn's disease does not appear to reduce the risk of
relapse over a 24 month period of follow-up.”
Osteoporosis is one of the most feared
long-term effects of steroid use. If the dose of prednisone is more than 7.5 mg
per day, treatment with etidronate and supplementation with calcium, phosphate,
vitamin D and other bone minerals may prevent bone loss and permit the continued
use of steroid therapy.
New agents have been introduced to treat
immune mediated diseases in general. The strategy of drug companies has been
varied, but the goal with each new agent is to block immune activation at some
level or another. While there may be benefits, the research and product hype can
be distracting. There is no easy way to block immune activity since the
mechanisms of immune reactivity are multiple and variable; the signals that
control immune activity are multiple, overlap and are sometimes contradictory.
The more effective immune blockers are, the more health damage they can do.
While initial studies show promising results MDs with years of experience will
hesitate and ask - do the benefits justify the risk? As a
general rule, the enthusiasm for new medications, especially expensive novel
drugs is often short-lived as evidence of limited efficacy and serious adverse effects emerge.
Monoclonal antibodies (infliximab, adalimumab, certolizumab pegol, natalizumab,
vedolizumab) are used in the treatment of moderate-to-severe active Crohn
disease or fistulizing disease unresponsive to other medical therapy.
Infliximab (Inflectra, Remicade) is a chimeric mouse-human monoclonal
antibody against tumor necrosis factor (TNF)-α that has been approved for the
treatment of pediatric Crohn's disease.
Adalimumab (Humira, Amjevita, adalimumab-atto) can induce
remission of moderate-to-severe active inflammatory Crohn's disease. This agent is a
recombinant human immunoglobulin (Ig) G1 monoclonal antibody specific for human
Certolizumab pegol (Cimzia) may be uded for moderate-to-severe Crohn's disease
in individuals whose condition has not responded to conventional therapies. It
is an anti–TNF-α blocker, and its action results in disruption of the inflammatory process.
Ustekinumab (Stelara) inhibits interleukin (IL)-12 and IL-23 cytokines,
which play a key role in inflammatory and immune responses. It is indicated for
adults with moderately to severely active Crohn's disease who have failed or were
intolerant to immunomodulators or corticosteroids. It is used in those who
failed or were intolerant to treatment with 1 or more TNF blockers.
A study investigated the use of an antibody preparation. The authors
stated that in chronic inflammatory conditions such as Crohn's disease, the
migration of leukocytes from the circulation into tissues and their
activation within inflammatory sites are mediated in part by 4 integrins.
A product containing monoclonal antibodies to 4 integrin (natalizumab) has been developed. Although the authors
reported some benefits from weekly intravenous administration in 248
patients with moderate-to-severe Crohn's disease, they reported that the
group given two infusions of 6 mg of natalizumab per kilogram did not have a
significantly higher rate of clinical remission (defined by a score of less
than 150 on the Crohn's Disease Activity Index) than the placebo group at
week 6. In another study of 905 patients with Crohn’s disease, the authors
concluded: “Induction therapy with natalizumab for Crohn's
disease resulted in small, nonsignificant improvements in response and
remission rates. Patients who had a response had significantly increased
rates of sustained response and remission if natalizumab was continued every
four weeks. The benefit of natalizumab will need to be weighed against the
risk of serious adverse events, including progressive multifocal
Immunosuppressants come with penalties:
- The drugs are often very expensive
- The side effects can be severe
- The long term effects both good and bad are unpredictable.
- The drugs are expensive to administer with intensify dependence on medical
facilities, laboratories and hospitals.
- Blocking immune function facilitates infection by a variety of
- Blocking immune activity may also increase the rate of cancer emergence.
Surgery is a last resort treatment. Many Crohn's disease patients
require surgery to rescue them from intestinal blockage, perforation,
abscess, or bleeding. Drainage of abscesses or resection of diseased bowel
are common surgical procedures. The bowel is cut above and below the
diseased area and reconnected. If the colon is badly diseased and
resected, an ileostomy is created by making a small opening in the
front of the abdominal wall. The end of the lower small intestine (ileum) is
brought to the skin's surface. A bag [or pouch] is worn over the
opening to collect waste, and the patient empties it periodically.
Surgery is never a solution for the disease. Inflammation tends to return in
areas of the intestine next to the area that has been removed.
You Can Do Better
Looking for a Solution? Do the Alpha Nutrition Program You can
order a Rescue Starter Pack. The book Food and Digestive Disorders describes
the features of Crohn's disease and explains how the inflamed digestive
tract is injured and does not work well. You have to assume that your body
is damaged and must heal.
Often a food holiday on Alpha ENF is the best way to begin
recovery and the Alpha Nutrition program is an ideal way to design a safer,
healthier long-term diet.