• IBD Medications: The Tried, the True, and the New

    Thanks to a growing array of medications, techniques and therapies, most children with inflammatory bowel disease (IBD) are enjoying steadily improving quality of life. Yet not all patients are fully sharing these gains.

    More work is needed to ensure that clinicians and families know about the latest, most effective therapies, says Dana Dykes, MD, a gastroenterologist at Cincinnati Children’s. With that goal in mind, Dykes discussed several trends in IBD treatment at the Family IBD Education Day, held March 2 in Mason, Ohio.

    “We have a number of excellent medications to control IBD and even more-effective treatments showing promise in clinical trials,” she says. “As our tools and knowledge continue to improve, we see the potential for changing the natural history of these diseases.”

    Reshaping the pyramid

    Many physicians follow a well-established treatment pyramid when trying to help children with IBD. The most commonly used tools at the base of the pyramid include nutritional therapy, antibiotics and the steroid budesonide (Entocort EC).

    If these approaches are not effective, treatment escalates to a class of drugs that act directly against the immune system’s inflammatory response. These medications include methotrexate and 6-MP/azathioprine. Prednisone, a stronger steroid, also is commonly used at this stage.

    Care for the hardest-to-control cases, at the tip of the pyramid, include four intensive approaches:

    • Surgery to remove damaged, dysfunctional intestine
    • IV-administered steroids to battle inflammation
    • Total parenteral nutrition (TPN) to provide liquid nutrition directly into the bloodstream
    • And the biologic agents Humira, Remicade and Cimza, which work against tumor necrosis factor (TNF), a key driver of IBD symptoms.

    The Tried and True

    Currently, only three therapies achieve mucosal healing – the gold standard of IBD treatment. They are immunomodulators; nutritional therapy with exclusive enteral formula feeding; and infliximab (Remicade) and similar biologic agents.

    • Nutritional therapy already is common in Europe, and merits more consideration in the US. It presents no toxic side effects and has been effective for 50-82 percent of children who have tried it.  However, adherence can be difficult to maintain and debate continues about how much success depends upon the location of the lesions.
    • Immunomodulators: Standard care in the US involves using corticosteroids to induce remission, then sustaining remission by using 6-mercaptopurine (6-MP), azathioprine or methotrexate (MTX). Up to 80 percent of Crohn’s patients and 50 percent of UC patients use at least one of these drugs.

      A recent clinical trial shows that newly diagnosed children with Crohn’s disease maintained better remission with significantly less corticosteroid exposure when they were treated with 6-MP. Low doses of MTX also have been shown to maintain remission.

      However, 6-MP’s risks can include bone marrow suppression, liver toxicity and an increased risk of lymphoma. MTX risks include scarring of the liver and lung inflammation. Both treatments require frequent blood counts and liver function tests.
    • Aminosalicylic acid: Clinical trials are exploring the safety and effectiveness of a class of medications including Asacol, Pentasa and others. Treatment can be delivered orally as rectal suppositories or via enema. These treatments can induce remission in 50-90 percent of adults with ulcerative colitis (UC) and children appear to have similar results. However, only Pentasa offers true drug release in the small intestine, which is a frequent site of activity in Crohn’s disease. This class of medications is not usually effective for maintenance in most patients with Crohn's.
    • Biologics provide antibodies (proteins) that neutralize the inflammatory response in the intestine. So far, more than 10,000 children and 750,000 adult IBD patients in the US have been treated with Remicade, the most commonly prescribed biologic.

      Humira is approved in the US for treating adult Crohn’s disease and ulcerative colitis. It is not yet approved for use in children, but it is used off-label to induce and maintain remission in children with Crohn’s and may work in patients who did not respond to Remicade. Simponi, another anti-TNFα agent, is approved for treating adults with UC and a third biologic, Cimza, is approved for adult use. However there is no good data on how these treatments perform in children.

      There is debate about starting biologic therapy earlier in the overall course of treatment. Earlier use may change the natural history of IBD and possibly avoid the need for surgery. However, this option must be carefully weighed because biologics present a small risk of developing lymphoma and other serious side effects.
    • Surgery remains an important treatment for people with IBD. Surgery is indicated in cases involving uncontrolled bleeding, obstruction, perforation, limited area of uncontrolled disease, medication intolerance, and to restore growth potential in selected individuals.

    The New

    Several new approaches that are not part of the traditional pyramid of care are being studied and some may eventually reach the market as safe and effective treatment options.

    • Probiotic therapy, which seeks to increase the “good” microorganisms that belong in the digestive system, appears to lessen the activity of the intestinal immune system. This approach plays a clear role in pouchitis and a possible role in maintaining remission in UC.
    • Studies are exploring the value of anti-integrin agents, such as natalizumab (Tysabri), and anti-interleukin agents such as ustekinumab (Stelara).
    • In small clinical trials, mostly involving people with Crohn’s disease, GM-CSF (Leukine), a chemical that activates certain types of white blood cells, is showing some promise. This therapy has achieved remission in 40 percent of cases versus 19 percent for placebo. However, the utility of this treatment remains up for debate.
    • Low dose naltrexone appears to partially block endorphins that affect the immune system and has some anti-TNF effect.
    • Other special diets are being studied, including a specific carbohydrate diet and a purported anti-inflammatory diet. These diets can help control symptoms but are difficult to follow. So far, no diet has shown true inflammation reduction.
    • Fecal transplant, as a way of replacing a patient’s dysfunctional gut flora with bacteria from a healthy donor, appears to be the most promising of these new therapies and is being the most actively investigated of all of the newer non-medical therapies. So far, we have limited knowledge about this therapy, but it may be beneficial particularly for ulcerative colitis.
  • Dana Dykes, MD.

    Dana Dykes, MD 

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