Crohn disease is a chronic condition, classified as a type of inflammatory bowel disease, that affects about 500,000 individuals in the United States This incidence has increased worldwide over the past several years.1,2

The condition causes inflammation in the digestive tract, which can lead to a plethora of symptoms, including abdominal pain and chronic diarrhea. Although there is no cure for Crohn disease, a variety of therapy options can manage the symptoms.

Causes and Risk Factors
Evidence suggests that Crohn disease may be caused by changes in the gut microbiome or disruption in the intestinal mucosa.3 However, studies have been unable to conclusively identify the full mechanism of the condition.4 Antibiotics, cigarette smoking, gastrointestinal infections, and nonsteroidal anti-inflammatory drugs (NSAIDs) may play a role in the development and exacerbation of Crohn disease. Heredity may also contribute, as Crohn disease is more common in patients with a family history of the condition.4

Signs and Symptoms
Crohn disease can cause a variety of symptoms (see Table1,3,4), and up to 80% of patients require hospitalization at some point during their clinical course.4



Treatment
Crohn disease treatment recommendations depend on condition location and severity. Treatment goals include controlling inflammation and preventing disease complications and recurrence. In patients with mild to moderately severe disease, sulfasalazine dosed 3 to 6 g daily is effective for treating colonic Crohn disease.4 In addition, corticosteroids are generally used to treat flare-ups and are shown to be effective for short-term use to alleviate signs and symptoms in patients with moderate to severe Crohn disease.4 Intravenous corticosteroids should be limited to severe Crohn disease cases. However, corticosteroids are not effective for maintenance therapy and are associated with adverse effects, such as bone loss, glaucoma, hypertension, increased blood glucose, and mood disorder.3 Mesalamine also should be avoided, though it remains widely prescribed, as it has not shown be effective.3,4

Antibiotics, such as ciprofloxacin and metronidazole, can be used as short-term treatment of perianal fistula and in combination with anti–tumor necrosis factor (TNF) drugs for perianal Crohn disease. Thiopurines (azathioprine, 6-mercaptopurine) are effective for steroid sparing and treatment for maintenance of remission. However, about 15% to 20% of patients discontinue thiopurines because of the AEs, which may include increased risk of certain cancers, nausea, pancreatitis, and vomiting.3 Also, methotrexate, up to 25 mg once weekly, as an intramuscular or subcutaneous injection is effective for steroid-dependent Crohn disease and for maintaining remission.4

Evidence suggests that anti-TNF medications (adalimumab, certolizumab pegol, or infliximab are the most effective therapies for moderate to severe Crohn disease.3 Some data that show infliximab is associated with fewer hospitalizations, steroid use, and surgeries than other anti-TNF drugs.3 The most common AEs associated with anti-TNF drugs are injection-site/infusion reactions and an increased risk of infection. Combination therapy of infliximab with thiopurines appears to have a synergistic effect, but there can be an increased risk of AEs.3

Medications targeting leukocyte trafficking, Entyvio (vedolizumab) and natalizumab (Tysabri), are effective in patients who have failed other therapies.4 Natalizumab carries a risk of progressive multifocal leukoencephalopathy, which is a rare but serious brain disease caused by the JC virus. Therefore, this drug should be limited to patients who are not seropositive for the anti-JC virus antibody and they should be checked before starting therapy and at least every 6 months thereafter. The interleukin inhibitor ustekinumab (Stelara) is used to treat moderate to severe Crohn disease in patients who have failed other treatments.5 Ustekinumab is administered as a 1-time weight-based infusion followed by subcutaneous injections every 8 weeks. Cyclosporine, mycophenolate mofetil, and tacrolimus should be avoided in patients with Crohn disease.4

Pharmacist Counseling Points
Pharmacists can play an important role in managing patients with Crohn disease. As part of an interdisciplinary team, they can assist with managing anxiety, depression, and stress, to improve quality of life in patients with Crohn disease.  Patients should be counseled to avoid NSAIDs to prevent disease exacerbation and those receiving corticosteroids closely monitored, and their doses tapered, to prevent adverse effects. Recommend acetaminophen when pain medications are needed, and encourage smoking cessation programs, as well.
 
Jennifer Gershman, PharmD, CPh, is a drug information pharmacist and Pharmacy Times® contributor who resides in South Florida.

References
  1. Mayo Clinic staff. Crohn’s disease. Mayo Clinic website. mayoclinic.org/diseases-conditions/crohns-disease/symptoms-causes/syc-20353304. Published March 8, 2018. Accessed September 5, 2018.
  2. Inflammatory bowel disease. American College of Gastroenterology website. patients.gi.org/topics/inflammatory-bowel-disease/#basics_2. Accessed September 5, 2018.
  3. Feuerstein JD, Cheifetz AS. Crohn disease: epidemiology, diagnosis, and management. Mayo Clin Proc. 2017;92(7):1088-1103. doi: 10.1016/j.mayocp.2017.04.010.
  4. Lichtenstein GR, Loftus EV, Isaacs KL, Regueiro MD, Gerson LB, Sands BE. ACG clinical guideline: management of Crohn’s disease in adults. Am J Gastroenterol. 2018;113(4):481-517. doi: 10.1038/ajg.2018.27.
  5. Verstockt B, Ferrante M, Vermeire S, Van Assche G. New treatment options for inflammatory bowel disease. J Gastroenterol. 2018;53(5):585-590. doi: 10.1007/s00535-018-1449-z.