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 bleeding.
The most commonly used drugs are:
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 TNF.
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: “Conclusions 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 leukoencephalopathy.”
Immunosuppressants come with penalties:
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.