Inflammatory Bowel Disease (Crohn’s and Ulcerative Colitis)
Conventional Treatment Options
Conventional treatments for IBD depend on disease location and severity, complications, and response to prior treatments. The goals of therapy are to control inflammation, correct nutritional deficiencies, and relieve symptoms such as abdominal pain, diarrhea, and rectal bleeding. It is important to note that an early diagnosis is associated with greater efficacy of less-aggressive drug regimens and thus a less oppressive burden of side effects. Therefore, seeing a physician as soon as symptoms emerge is suggested. Therapy may include drugs, surgery, or a combination of approaches.
The following drugs can be used to treat IBD:
- Aminosalicylates are drugs that contain 5-aminosalicyclic acid (5-ASA) and help control local inflammation of the gut. These drugs are primarily used to treat mild to moderate IBD and help with remission maintenance (Bebb 2004). Adverse effects include nausea, vomiting, heartburn, diarrhea, and headache. 5-ASA agents such as olsalazine, mesalamine, and balsalazide have fewer adverse effects and may be used by people who cannot take sulfasalazine. Balsalazide is converted in the colon to mesalamine, and has been shown to reduce bowel inflammation, diarrhea, rectal bleeding, and stomach pain (Muijsers 2002). 5-ASA agents are given orally or rectally (through an enema or in a suppository), depending on the location of the inflammation. Sulfasalazine interferes with folate absorption, so those taking this drug should also supplement with folate (Jansen 2004). Use of aminosalicylate drugs or antibiotics may deplete vitamin K in IBD patients, and oral supplementation of this vitamin relieves this problem (Krasinski 1985).
- Glucocorticoids or cortiocosteroids (such as prednisone and hydrocortisone) reduce inflammation. They are used to treat more severe cases of IBD and to end acute attacks. Glucocorticoids can be given orally, intravenously, or rectally (through an enema or in a suppository), depending on the location of the inflammation. These drugs can cause serious adverse effects, including increased risk of infection, diabetes, high blood pressure, bone loss, kidney suppression, and ulcers. Less serious adverse effects include weight gain, acne, facial hair, and mood swings. They are not recommended for long-term use and are typically replaced with 5-ASA drugs once remission has been induced. Calcium and vitamin D may help combat glucocorticoid-induced bone loss (Homik 2000).
Immune system suppressors
- Antimetabolites such as azathioprine and mercaptopurine prevent replication of inflammatory T cell lines. They are used to treat people with IBD who have not responded to 5-ASAs or glucocorticoids, or who are dependent on glucocorticoids. However, antimetabolites are slower acting than other types of drugs. Anyone taking these drugs should be monitored for complications such as pancreatitis, hepatotoxicity, reduced white blood cell count, and an increased risk of infection. A genetic test known as thiopurine methyltransferase (TMPT) genotyping can help predict who will have severe adverse effects from these drugs (Newman 2011).
- Cyclosporine. This drug inhibits T cell-mediated immune responses, thus reducing the immune reaction that underlies inflammation. It blocks a number of inflammatory cytokines, including TNF-α and various interleukins. Because cyclosporine is associated with significant risk of toxicity, its use is limited to severe ulcerative colitis or Crohn’s disease.
- Methotrexate. The cancer chemotherapy drug methotrexate is used in Crohn’s patients that are steroid dependent or have not responded to glucocorticoids (Preiss 2010). It can be given orally or by weekly injections under the skin or into the muscles (Xu 2004). Methotrexate is most effective for maintenance of remission when given as an injection (Patel 2009). This drug also interferes with folate metabolism. Folate should be supplemented with it, particularly to help prevent colorectal cancer, which this drug otherwise promotes (Patel 2009; Coogan 2007).
- Biologics / TNF-inhibitors. During flare-ups, levels of the inflammatory cytokine TNF-α become elevated. This has led to interest in antibodies such as infliximab, adalimumab, certolizumab pegol, and golimumab that block TNF-α. These have all been shown to induce and maintain remission including mucosal healing and restoration of gut barrier function (Malik 2012; Behm 2008; Gisbert 2006). However, these drugs are very expensive, have not been shown to prevent colectomy in severe ulcerative colitis (Aratari 2008), and may cause autoimmune diseases, cancer, infections, and viral reactivation syndromes including shingles (Colombel 2004).
- The following immunosuppressive agents may be considered as well: tacrolimus, mycophenolate mofetil and thalidomide.
- Cromolyn sodium. This drug is modified from the natural compound known as khellin and works as a mast cell-stabilizing anti-inflammatory. One clinical trial found that daily administration of 200 mg cromolyn sodium rectally for 15 days induced remission in almost all patients with ulcerative colitis, and this was maintained in 93% of them when they took 240 mg daily for 2—3 years (Malolepszy 1977). In another trial, oral cromolyn sodium at a dose of 1,500 mg daily relieved diarrhea more effectively than an elimination diet (in which problematic foods are avoided) in patients with irritable bowel syndrome (Stefanini 1995). This indicates that cromolyn may ameliorate reactivity to some foods – a factor that possibly drives some inflammation in inflammatory bowel disease. As is so often the case with drugs that are off patent and thus not very profitable, no company or government has seen fit to fund further research on this safe and cheap drug for inflammatory bowel disease.
- Naltrexone. Originally developed to help treat heroin addiction, lower doses of naltrexone have shown a range of remarkable immunological activities. A placebo-controlled study on the use of low-dose naltrexone (4.5 mg per day at bedtime) suggested that the drug could resolve mucosal inflammation and induce clinical remission in patients with moderate-to-severe Crohn’s disease (Smith 2011). This confirms one earlier uncontrolled study of low-dose naltrexone’s efficacy for Crohn’s disease (Smith 2007). Naltrexone appears to relieve inflammatory bowel disease in part by decreasing expression of proinflammatory cytokines and promoting tissue repair (Matters 2008). At low dosages, the drug may cause drowsiness, but other side effects are uncommon.
In severe cases of Crohn’s disease, abscesses can develop in chronically inflamed tissues. These abscesses can grow and tunnel through tissue barriers to produce fistulas, or channels between organs. Almost half of patients who have Crohn’s disease develop perianal disease involving anal fissures, perianal abscesses, and fistulas. These symptoms seldom respond well to conventional therapies (Braunwald 2001; McNamara 2004). Surgery may be required in a high percentage of these patients (Danelli 2003). Complications are frequent.
Surgery may also be recommended to remove severely inflamed portions of the intestinal tract. The goal of surgery is to preserve as much of the intestine as possible. Surgery commonly involves the colon or small intestine. Occasionally, the end of the intestine that has been left in place will need to be brought to the skin's surface to allow waste excretion. When this procedure involves the small intestine, it is called an ileostomy. If the procedure involves the colon, it is called a colostomy. Although Crohn's disease may recur after surgery, the symptoms are likely to be less severe and less debilitating than they were previously (Hwang 2008). Elemental diets (in which simple molecules like glucose and individual amino acids replace whole foods) have been shown to reduce recurrence of Crohn’s disease when employed after surgery (Yamamoto 2007; Esaki 2005).
Newer surgeries, however, have been developed that can preserve fecal continence by using part of the ileum to create a pouch that is connected to the intact rectal sphincter (Hwang 2008). In a thorough review, the use of probiotic supplements was able to significantly reduce the occurrence of pouchitis, or inflammation of the reservoir formed upon surgical creation of an ilio-anal pouch, by 96% compared to placebo after surgery among ulcerative colitis patients (Elahi 2008).