Overview of medical therapy in IBD

Hi Everyone!

Pat will be providing an overview of Inflammatory Bowel Disease, mainly focusing on Crohn's Disease (CD) and Ulcerative Colitis (UC). To go along with this, I wanted to provide an overview of the current treatments used in IBD, as this is not something we will directly review in our articles.

The overall goal of treatment in IBD is to stop the abnormal inflammatory response that is responsible for the symptoms, and aid in the induction and maintenance of remission. There is debate as to the approach taken in medical therapy. Some feel it better to start with less aggressive medications and work up the line to achieve the optimal medication for the individual patient. Others feel that starting with more aggressive medications at onset of disease may help to prevent irreversible bowel injury and lead to a better long-term outcome. However, I simply would like to give you an overview of the available medications. As we learn more about this disease over the next few weeks, the door is obviously wide open for debates on treatment approaches.

Aminosalicylates

Aminosalicylates are aspirin-like medications that contain 5-aminosalicylic acid (5-ASA), a potent anti-inflammatory agent. 5-ASA agents likely have multiple anti-inflammatory effects including inhibition of cyclooxygenase, lipoxygenase, B-cells and multiple inflammatory cytokines. These agents are usually used to treat mild to moderate symptoms, and are availiable in both oral and topical forms. More solid data exists for the use of 5-ASA agents in the effective treatment of UC than in CD. Their efficacy of treatment for CD is much less clear, and often is determined by the location of the disease in the GIT.

Antibiotics

Antibiotics such as Metronidazole and Ciprofloxacin are sometimes used to treat mild to moderate symptoms of CD; however, the evidence to support their mechanism of action is limited. Antibiotics are deemed more appropriate for treatment of perianal disease and fistulas in CD because of the risk for septic complications. In contrast, antibiotics are rarely used in the treatment of active UC.

Corticosteroids

These steroids act in our body by binding to glucocorticoid receptors in many of our different cell types and activating glucocorticoid-responsive elements (GREs). This leads to a wide array of effects on the immune system including inhibition of the recruitment and proliferation of lymphocytes and monocytes and a decreased production of inflammatory mediators (cytokines, prostaglandins, etc). Corticosteroids are effective for inducing remission in CD and UC; however, long term use to maintain remission is not recommended due to their numerous side effects. One particular steroid, budesonide, is a non-systemic acting glucocorticoid that may be used for the maintenance of remission. However, proper dosing schedules or amounts have yet to be determined.

Immunomodulators

Two immunomodulators currently used in the treatment of CD and UC are 6-Mercaptopurine and Azathioprine. The metabolites of these medications interfere with nucleic acid synthesis, and they have anti-proliferative effects on activated lymphocytes. Often immunomodulators are used when the disease is moderate to severe or when a patient is unresponsive to other drug treatments (5-ASAs or steroids). These medications are effective in both induction and maintenance of remission; however, their onset of action is typically 3-4 months, so other medications must be coupled with these initially.

Methotrexate (MTX) is another immunomodulator primarily used in treatment for CD. It acts as a competitive inhibitor or dihydrofolate reductase, one of the key enzymes necessary for folate production. As a result, MTX interferes with DNA synthesis and has multiple anti-inflammatory effects as it works as an immunosuppresant.

Since all of these immunomodulators interfere with the immune system, patients are at an increased risk of infection and must have their white blood cell counts monitored.

Biologic Agents

These agents are a group of medications that act in a variety of ways to inhibit TNF-alpha. TNF-alpha is a cytokine that mediates multiple pro-inflammatory processes central to the pathogenesis of IBD. Two common biologic agents used in treatment of IBD are infliximab and adalimumab. Infliximab is an intravenous infusion whereas adalimumab is administered subcutaneously. Indications for the usage of these therapies include both the induction and maintenance of remission for patients with moderate to severe disease. These biologic agents have also proved very useful in the treatment of fistulas and extra intestinal manifestations in CD.

Ok, well I figure this will at least give everyone some good introductory information on medical therapy in IBD. I by no means presented everything about the medical treatment, and just like in many other situations, treatment must be individualized to the patient.

References

Kozuch PL, Hanauer SB. Treatment of inflammatory bowel disease: A review of medical therapy. World J Gastroenterol 2008; 14(3):354-377.

Cummings JR, Keshav S, Travis SP. Medical management of Crohn's disease. BMJ 2008; 336:1062-6.