There are several management options for Crohn’s disease. Treatment goals aim to induce and maintain remission, improve nutrition, optimize growth and sexual development in children, and minimize the side effects of treatments for symptoms. Management not only involves symptom reduction, but promotes intestinal healing.

Drug Therapy

Glucocorticosteroids
Glucocorticosteroids are used to treat moderate to severe CD, when other medicines have stopped working to prevent acute exacerbations. Glucocorticosteroids are a group of corticosteroids, a class of steroid hormones. These drugs are used to reduce inflammation by inducing production of protein lipocortin-1. Lipocortin-1 suppresses the activity of phospholipase A2, an enzyme that releases fatty acids called arachidonic acid. Arachidonic acid is then modified by cyclooxygenase into eicosanoids like prostaglandins and leukotrienes. These eicosanoids mediate inflammation. Thus, glucocorticosteroids reduce inflammation by blocking the production of inflammatory mediators. Long-term use of glucocorticoids can have harmful effects such as suppression of a vital hormone pathway and development of steroid-dependence. Thus, these treatments are only used in the short-term to put the disease in temporary remission. Once the patient is in remission, the patient is tapered off the treatment. They can be taken as oral pills, enemas, suppositories or topical creams, depending on the nature of the disease.

Side effects of glucocorticoids are relatively mild in the short term and cause increased appetite and restlessness. Patients may also experience hives, symptoms of infections (sore throat, fever, sneezing, coughing, etc), persistent abdominal pain, nausea or vomiting, bloody or dark stools, rapid weight gain, blurred vision, eye pain, muscle cramps or weakness, acne, increase in thirst, and frequent urination.

Glucocorticoids used to treat CD include:

• Budesonide (Brand name: Entocort)
• Dexamethasone
• Hydrocortisone (Brand names: Cortef, Cortenema, Proctofoam)
• Methylprednisolone
• Prednisolone (Brand name: Orapred)
• Prenisone

Aminosalicylates
Aminosalicylates are drugs that contain a compound called 5-aminosalicylic acid (5-ASA), thus the treatment is sometimes referred to as 5-ASA. Unlike glucocorticoids, 5-ASA is designed specifically to treat IBD. 5-ASA reduces inflammation in the lining of the intestines to induce remission and may also work to prevent future flare-ups. 5-ASA is an analog to salicylate, and is thought to work using a mechanism other than that of non-steroidal anti-inflammatory drugs (NSAIDs) by inhibiting production of inflammatory mediators by cyclooxygenase and lipoxygenase.

Aminosalicylates used to treat CD include:

• Balsalazide (Brand name: Colazal, Gyazo)
• Mesalamine (Brand name: Asacol, Pentasa, Canasa, Rowasa)
• Olsalazine (Brand name: Dipentum)
• Sulfasalazine (Brand name: Azulfidine)

5-ASA can be delivered in various ways. The formulation depends largely on the location of the disease. Mesalamine comes as an oral capsule designed to release on a delay (Asacol) or to provide prolonged release (Pentasa) in order to treat the colon. 5-ASA can also be provided as an enema or suppository to treat other IBD. There are some risks and side effects associated with the treatment. An overdose may cause dizziness, drowsiness, headaches, unconsciousness, a lack of appetite, abdominal pain, nausea, vomiting or development of life-threatening conditions such as hemolytic anemia, agranulocytosis, dermatitis, acidosis and jaundice.

Common side effects include:

• Nausea
• Abdominal pain
• Headache
• Dizziness
• Fatigue
• Inflammation of the liver (Hepatitis (rare case))
• Inflammation of the pancreas (Pancreatitis (rare case))

Antibiotics
Antibiotics are commonly used to treat mild to moderate CD. They work to treat inflammation by reducing bacteria levels in the intestines and reducing the intestinal immune response. Antibiotics may also be used to treat specific complications associated with the disease, such as anal abscesses, fistulas and pouchitis. The full course of the antibiotic should be taken even after the symptoms have cleared up, to prevent them from returning. Not finishing the course of antibiotic can result in treatment failure or antibiotic resistance.

Commonly used antibiotics for CD include:

• Ciprofloxacin (Brand name: Cipro)
• Metronidazole (Brand name: Flagyl)

Common side effects of antibiotics (particularly at higher doses) include:

• Nausea
• Loss of appetite
• Metallic taste
• Diarrhea
• Dizziness
• Headaches
• Dark urine
• Numbness in the hands (rare)
• Seizures (rare)
• Nausea
• Stomach pain
• Sensitivity to sunlight
• Tendon rupture (rare)
• Confusion
• Depression
• Hallucinations
• Rapid heartbeat

Immunosuppressive Drugs
Immunosuppressive drugs are commonly prescribed when other treatments have failed to work. They limit the activity of the immune system in the intestines in order to reduce inflammation. These drugs may also be used to prevent future flare-ups and to treat complications of CD such as fistulas. Once in the body, these treatments are converted into nucleotide components like compounds. The compounds are incorporated into newly made DNA, to block replication, and thus blocks activity of an enzyme involved in cell reproduction called glutamine-phosphoribosylpyrophosphate amidotransferase (GPAT). Cells that replicate quickly are most affected by this inhibition. This includes immune cells T cells and B cells. The pseudo-nucleotides also bind to Rac-1 to block synthesis of anti-apoptotic protein Bcl-xL in immune cells, causing them to undergo programmed cell death.

Commonly used immunosuppressive drugs include:

• Azathioprine (Brand name: Imuran)
• Methotrexate
• Mercaptopurine

The latter two treatments are primarily used to prevent future flare-ups, and can take months to start working.

Common side effects include:

• Nausea
• Vomiting
• Reduced resistance to infection
• Diarrhea
• Fatigue
• Liver scarring (with long-term use)

Biologics or tumor necrosis factor (TNF) alpha inhibitors
Immunotherapy is typically the first line of treatment for CD. This involves modification of the immune system.

Biologics are therapies that block the body’s immune response to antigens or other harmful substances. In the case of CD, the immune system perceives health host tissue in the intestine as harmful invaders, causing inflammation. Biologics are particularly used in cases of moderate to severe CD that does not respond to other treatments and to treat fistulas. In the case of tumor necrosis factor (TNF) alpha inhibitors, the biologics target is TNF alpha—a protein produced in response to inflammation that promotes an immune response in the body. High TNF levels can cause inflammation in the intestines as well as the joints and the skin. TNF alpha inhibitors block the activity of the protein to reduce inflammation.

Biologics are different from other immunosuppressive therapies, in that they target specific proteins that cause inflammation in the intestines.

Commonly used biologics for CD include:

• Adalimumab (Humira)
• Adalimumab-atto (Amjevita), a biosimilar to Humira
• Certolizumab (Cimzia)
• Golimumab (Simponi)
• Infliximab (Remicade)
• Infliximab-abda (Renflexis), a biosimilar to Remicade
• Infliximab-dyyb (Inflectra), a biosimilar to Remicade
• Natalizumab (Tysabri)
• Ustekinumab (Stelara)
• Vedolizumab (Entyvio)

Biologics tend to have fewer and less severe side effects. In rare situations, they may cause lymphoma and blood disorders. They can also result in the following at the site of injection:

• Redness, itching, bruising, pain, swelling at the site of injection
• Headaches
• Fevers
• Chills
• Trouble breathing
• Low blood pressure
• Hives
• Rash
• Stomach pain
• Back pain
• Nausea
• Coughing
• Sore throat

Because biologics can be expensive, these are typically only prescribed in moderate to severe cases of CD after treatment with other immunosuppressive drugs.