Several classes of medications are helpful for inflammatory bowel disease (IBD). Details of their selection and use are discussed under each disorder (see Crohn disease treatment and ulcerative colitis treatment).
(See also Overview of Inflammatory Bowel Disease.)
5-Aminosalicylic Acid (5-ASA, Mesalamine)
5-ASA blocks production of prostaglandins and leukotrienes and has other beneficial effects on the inflammatory cascade. Because 5-ASA is active only intraluminally and is rapidly absorbed by the proximal small bowel, it must be formulated for delayed absorption when given orally.
Medications that complex 5-ASA with other vehicles seem almost equally effective but have fewer adverse effects. (a 5-ASA dimer) and
Other formulations of 5-ASA use delayed-release and/or extended-release coatings to delay release of the drug until entry into the distal ileum and colon. Combination delayed-release and extended-release formulations may be given once a day; their less frequent dosing may improve the patient's adherence to taking them. All of these formulations of 5-ASA are therapeutically roughly equivalent.
5-ASA is also available as a suppository or enema for proctitis and left-sided colon disease. These rectal preparations are effective for both acute treatment and long-term maintenance in proctitis and proctosigmoiditis and they have incremental benefit in combination with oral 5-ASA. Patients who cannot tolerate enemas due to rectal irritation should be given 5-ASA foam.
Corticosteroids
Corticosteroids, beginning at high doses, are useful for acute flare-ups of most forms of IBD when 5-ASA compounds are inadequate. However, corticosteroids are not appropriate for maintenance.
or is used for severe disease; or may be used for moderate to severe disease. Treatment is continued until symptoms remit (usually 7 to 28 days) and then tapered weekly to 20 mg once a day. Treatment is then further tapered by 2.5 to 5 mg weekly depending on clinical response, while instituting maintenance therapy with 5-ASA or immunomodulators. Adverse effects of short-term corticosteroids in high doses include hyperglycemia, hypertension, insomnia, hyperactivity, and acute psychotic episodes.
may be used for proctitis and left-sided colon disease; an enema solution is given once a day or twice a day. The enema should be retained in the bowel as long as possible; instillation at night, with the patient lying on the left side with hips elevated, may prolong retention and extend distribution. Treatment, if effective, should be continued daily for about 2 to 4 weeks, then every other day for 1 to 2 weeks, and then gradually discontinued over 1 to 2 weeks.
is a corticosteroid with a high (>
cirrhosis because bioavailability and clinical effects may be enhanced.
Immunomodulating Medications
Azathioprine and 6-mercaptopurine
The most common adverse effects are nausea, vomiting, and malaise. Signs of bone marrow suppression must be monitored with regular white blood cell counts (biweekly for 1 month, then every 1 to 2 months). Pancreatitis or high fever occurs in about 3 to 5% of patients; either is an absolute contraindication to rechallenge. Hepatotoxicity is rarer and can be screened for by blood tests every 6 to 12 months. These drugs are associated with increased risk of lymphoma and nonmelanoma skin cancers.
8 red blood cells (RBCs). Myelotoxicity can occur when 6-TG levels are > 450. Hepatotoxicity can occur when 6-MMP levels are > 5700 picomoles per 8 × 108 RBCs. The concentrations of metabolites are also useful in nonresponding patients to distinguish lack of adherence from resistance.
Methotrexate
Adverse effects
Cyclosporine and tacrolimus
which blocks lymphocyte activation, may benefit patients with severe ulcerative colitis unresponsive to corticosteroids and biologic agents and who may otherwise require colectomy. Its only well-documented use in Crohn disease is for patients with refractory fistulas or pyoderma. Long-term use (>Pneumocystis jirovecii
Biologic Agents
Anti-TNF medications
is useful for Crohn disease and ulcerative colitis and is given as a single IV infusion of 5 mg/kg over 2 hours. It is followed by repeat infusions at weeks 2 and 6. Subsequently, it is given every 8 weeks. To maintain remission in many if not most patients, the dose needs to be increased or the interval needs to be shortened within a year or so. The accepted therapeutic serum level is > 5 mcg/mL.
is useful for Crohn disease and ulcerative colitis. It is given with an initial loading dose of 160 mg subcutaneously and then 80 mg subcutaneously at week 2. After that dose, 40 mg subcutaneously is given every 2 weeks. The accepted therapeutic serum level is > 7.5 mcg/mL.
Certolizumab is useful for Crohn disease. It is given as 400 mg subcutaneously every 2 weeks for three doses and then every 4 weeks for maintenance. The accepted therapeutic serum level is > 20 mcg/mL.
is beneficial for patients with ulcerative colitis. It is given with an initial loading dose of 200 mg subcutaneously and then 100 mg at week 2. After that dose, 100 mg is given every 4 weeks.
Several patients have died of sepsis after anti-TNF use, so these drugs are contraindicated when uncontrolled bacterial infection is present. Also, tuberculosis (TB) and hepatitis B reactivation has been attributed to anti-TNF drugs; therefore, screening for latent TB (with tuberculin skin tests and/or interferon-gamma release assay) and for hepatitis B is required before therapy. Documenting immunity to varicella is advised. Some physicians also recommend serologic testing for Epstein-Barr virus and cytomegalovirus.
Lymphoma and possibly other cancers (eg, nonmelanoma skin cancer), demyelinating disease (eg, multiple sclerosis, optic neuritis), heart failure, and liver and hematologic toxicity are other potential concerns with anti-TNF drug treatment.
Other biologic agents
Several immunosuppressive interleukins and anti-interleukin antibodies also may decrease the inflammatory response and are being studied for Crohn disease.
and progressive multifocal leukoencephalopathy
an anti-IL-12/23 antibody, is available for patients with moderate to severe Crohn disease or ulcerative colitis. The initial loading dose is a single IV dose based on weight: < 55 kg: 260 mg; 55 to 85 kg: 390 mg; > 85 kg: 520 mg.
After the loading dose, patients are given a maintenance dose of 90 mg subcutaneously every 8 weeks.
Other anticytokine, anti-integrin, small-molecule agents, and growth factors are under investigation, as is leukopheresis therapy to deplete activated immunocytes.
, an anti-IL-23 antibody, is available for patients with moderate to severe Crohn disease. The induction dose is 600 mg IV at weeks 0, 4, and 8. The maintenance dose is 180 to 360 mg subcutaneous at week 12 and every 8 weeks thereafter. Using the lowest dose that maintains endoscopic remission is recommended. Liver tests should be done at baseline and during the induction period.
Biosimilars are biologic medications that are very similar to a reference biologic product. Biosimilars of the anti-TNF drugs have been commercialized.
Small-molecule agents
Small-molecule agents are medications with molecular weight < 1 kilodalton. Some of these are now in use or under development for the management of IBD. They are given orally and lack the immunogenicity associated with monoclonal antibodies.
is a small-molecule agent that inhibits Janus kinase 1–3 and is available for adult patients with moderate to severe ulcerative colitis. The initial dosage of the immediate-release form is 10 mg orally 2 times a day for at least 8 weeks, followed by 5 or 10 mg orally 2 times a day. The initial dosage of the extended-release form is 22 mg orally once a day for at least 8 weeks, followed by 11 mg orally once a day. Potential adverse effects include elevated cholesterol levels, diarrhea, headache, shingles (herpes zoster), augmented blood creatine phosphokinase, nasopharyngitis, rash, and upper respiratory tract infection. Other uncommon adverse effects include cancer and opportunistic infections. In addition, the U.S. Food and Drug Administration warned of an increased risk of fatal pulmonary embolism and death in patients with rheumatoid arthritis.
Antibiotics and Probiotics
Antibiotics
Antibiotics may be helpful in Crohn disease but are of limited use in ulcerative colitis, except in toxic colitis
Probiotics
Various nonpathogenic microorganisms (eg, commensal Escherichia coli, species, Saccharomyces) given daily serve as probiotics and may be effective in preventing pouchitis, but other therapeutic roles have yet to be clearly defined. Therapeutic infestation with the parasite Trichuris suis has been tried in an effort to stimulate T2-helper cell immunity and may decrease disease activity in ulcerative colitis.
