Several classes of medications are used to treat inflammatory bowel disease (IBD). Details of their selection and use are discussed under each disorder (see Crohn disease treatment, ulcerative colitis treatment). The classification of medications is listed in the table ).
Medications for Inflammatory Bowel Disease
Category | Mechanism | Medication |
|---|---|---|
Glucocorticoids | Regulation of gene expression | Hydrocortisone (IV)Hydrocortisone (IV) Methylprednisolone (IV)Methylprednisolone (IV) Prednisone (oral)Prednisone (oral) Prednisolone (oral)Prednisolone (oral) Budesonide (oral)Budesonide (oral) Budesonide MMX (enteric coated slow release)Budesonide MMX (enteric coated slow release) Hydrocortisone (enema or foam)Hydrocortisone (enema or foam) |
Immunomodulators (antimetabolites) | Thiopurines | AzathioprineAzathioprine 6-Mercaptopurine (6MP)6-Mercaptopurine (6MP) |
Antifolate | MethotrexateMethotrexate | |
Biologic Agents | Anti-TNF antibodies | InfliximabInfliximab AdalimumabAdalimumab Certolizumab GolimumabGolimumab |
Antibodies to leukocyte adhesion molecules | VedolizumabVedolizumab NatalizumabNatalizumab | |
Anti-IL-23 and related antibodies | MirikizumabMirikizumab RisankizumabRisankizumab Ustekinumab (anti-IL 12/23)Ustekinumab (anti-IL 12/23) Guselkumab (anti-p19 subunit of IL23))Guselkumab (anti-p19 subunit of IL23)) | |
Small Molecules | Janus kinase (JAK) inhibitors | TofacitinibTofacitinib UpadacitinibUpadacitinib |
Sphingosine 1-phosphate (S1P) receptor modulators | OzanimodOzanimod EtrasimodEtrasimod | |
Other Immunosuppressants | Calcineurin inhibitors | CyclosporineCyclosporine TacrolimusTacrolimus |
(See also Overview of Inflammatory Bowel Disease.)
5-Aminosalicylic Acid (5-ASA, Mesalamine)
5-ASA (mesalaminemesalamine) is primarily used as a first-line medication for induction and maintenance of remission in mild to moderate ulcerative colitis (1).
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.
Sulfasalazine,Sulfasalazine, the original agent in this class, delays absorption by complexing 5-ASA with a sulfa moiety, sulfapyridine. The complex is cleaved by bacterial flora in the lower ileum and colon, releasing the 5-ASA. The sulfa moiety, however, causes numerous adverse effects (eg, nausea, dyspepsia, headache), interferes with folate (folic acid) absorption, and occasionally causes serious adverse reactions (eg, hemolytic anemia or agranulocytosis and, rarely, hepatitis, pneumonitis, or myocarditis). Reversible decreases in sperm count and motility occur in up to 80% of men. If used, sulfasalazine should be given with food. Patients should take daily folate supplements (1 mg orally) and have complete blood count and liver tests every 6 to 12 months. Acute interstitial nephritis secondary to mesalamine occurs rarely; periodic monitoring of renal function is advisable because most cases are reversible if recognized early. the original agent in this class, delays absorption by complexing 5-ASA with a sulfa moiety, sulfapyridine. The complex is cleaved by bacterial flora in the lower ileum and colon, releasing the 5-ASA. The sulfa moiety, however, causes numerous adverse effects (eg, nausea, dyspepsia, headache), interferes with folate (folic acid) absorption, and occasionally causes serious adverse reactions (eg, hemolytic anemia or agranulocytosis and, rarely, hepatitis, pneumonitis, or myocarditis). Reversible decreases in sperm count and motility occur in up to 80% of men. If used, sulfasalazine should be given with food. Patients should take daily folate supplements (1 mg orally) and have complete blood count and liver tests every 6 to 12 months. Acute interstitial nephritis secondary to mesalamine occurs rarely; periodic monitoring of renal function is advisable because most cases are reversible if recognized early.
Medications that complex 5-ASA with other vehicles seem almost equally effective but have fewer adverse effects (2). OlsalazineOlsalazine (a 5-ASA dimer) and balsalazidebalsalazide (5-ASA conjugated to an inactive compound) are cleaved by bacterial azoreductases (as is sulfasalazine). These medications are activated mainly in the colon and are less effective for proximal small-bowel disease. Olsalazine sometimes causes diarrhea, especially in patients with pancolitis. This problem is minimized by gradual escalation of dose and administration with meals.(5-ASA conjugated to an inactive compound) are cleaved by bacterial azoreductases (as is sulfasalazine). These medications are activated mainly in the colon and are less effective for proximal small-bowel disease. Olsalazine sometimes causes diarrhea, especially in patients with pancolitis. This problem is minimized by gradual escalation of dose and administration with meals.
Other formulations of 5-ASA use delayed-release and/or extended-release coatings to delay release of the medication 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.
5-aminosalicylic acid references
1. Rubin DT, Ananthakrishnan AN, Siegel CA, Barnes EL, Long MD. ACG Clinical Guideline Update: Ulcerative Colitis in Adults. Am J Gastroenterol. 2025;120(6):1187-1224. Published 2025 Jun 3. doi:10.14309/ajg.0000000000003463
2. Ko CW, Singh S, Feuerstein JD, et al. AGA Clinical Practice Guidelines on the Management of Mild-to-Moderate Ulcerative Colitis. Gastroenterology. 2019;156(3):748-764. doi:10.1053/j.gastro.2018.12.009
Glucocorticoids
Glucocorticoids, beginning at high doses, are useful for acute flares of most forms of IBD. While useful for induction of remission, glucocorticoids are generally not appropriate for maintenance (1, 2).
IV hydrocortisoneIV hydrocortisone or methylprednisolonemethylprednisolone is used for severe disease; oral prednisoneoral prednisone or prednisoloneprednisolone may be used for moderate to severe disease. Treatment is continued until symptoms remit (usually 7 to 28 days) and then tapered weekly depending on clinical response, while instituting maintenance therapy with other medications. Adverse effects of short-term glucocorticoids in high doses include hyperglycemia, hypertension, insomnia, hyperactivity, and acute psychotic episodes.
Hydrocortisone enemas or foamHydrocortisone enemas or foam 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.
BudesonideBudesonide is a glucocorticoid with a high (> 90%) first-pass liver metabolism; thus, oral administration may have a significant effect on gastrointestinal tract disease but minimal adrenal suppression. Budesonide may be effective in maintaining remission for 8 weeks but has not yet proved effective for long-term maintenance. The medication is available for small-bowel Crohn disease, and an enteric-coated, delayed-release form (budesonide MMX) is available for mild to moderate left-sided ulcerative colitis (90%) first-pass liver metabolism; thus, oral administration may have a significant effect on gastrointestinal tract disease but minimal adrenal suppression. Budesonide may be effective in maintaining remission for 8 weeks but has not yet proved effective for long-term maintenance. The medication is available for small-bowel Crohn disease, and an enteric-coated, delayed-release form (budesonide MMX) is available for mild to moderate left-sided ulcerative colitis (2). It is also available as an enema or rectal foam preparation.
All patients started on glucocorticoids (including budesonide) should be given oral vitamin D 400 to 800 units/day and calcium 1200 mg/day. Glucocorticoids should be used with caution in patients with chronic liver disease, including All patients started on glucocorticoids (including budesonide) should be given oral vitamin D 400 to 800 units/day and calcium 1200 mg/day. Glucocorticoids should be used with caution in patients with chronic liver disease, includingcirrhosis, because bioavailability and clinical effects may be enhanced.
Glucocorticoids references
1. Rubin DT, Ananthakrishnan AN, Siegel CA, Barnes EL, Long MD. ACG Clinical Guideline Update: Ulcerative Colitis in Adults. Am J Gastroenterol. 2025;120(6):1187-1224. Published 2025 Jun 3. doi:10.14309/ajg.0000000000003463
2. Lichtenstein GR, Loftus EV, Afzali A, et al. ACG Clinical Guideline: Management of Crohn's Disease in Adults. Am J Gastroenterol. 2025;120(6):1225-1264. Published 2025 Jun 3. doi:10.14309/ajg.0000000000003465
Immunomodulating Medications
The antimetabolites azathioprine and 6-mercaptopurine (thiopurines), and methotrexate, are used in combination therapy with The antimetabolites azathioprine and 6-mercaptopurine (thiopurines), and methotrexate, are used in combination therapy withbiologic agents, and for maintenance therapy in patients with Crohn disease in whom remission was induced with glucocorticoids (1, 2). They are generally not used as monotherapy for induction of remission.
Azathioprine and 6-mercaptopurine
Azathioprine and its metabolite 6-mercaptopurine inhibit T-cell function and may induce T-cell apoptosis. They are effective long-term and may diminish glucocorticoid requirements and maintain remission for years. These medications often require 1 to 3 months to produce clinical benefits, so glucocorticoids cannot be completely withdrawn until at least the second month. Dosage varies depending on individual metabolism. The dose of azathioprine or 6-mercaptopurine should be reduced by 50% and adjusted accordingly based on clinical response and hematologic monitoring in patients who are intermediate metabolizers. Azathioprine and its metabolite 6-mercaptopurine inhibit T-cell function and may induce T-cell apoptosis. They are effective long-term and may diminish glucocorticoid requirements and maintain remission for years. These medications often require 1 to 3 months to produce clinical benefits, so glucocorticoids cannot be completely withdrawn until at least the second month. Dosage varies depending on individual metabolism. The dose of azathioprine or 6-mercaptopurine should be reduced by 50% and adjusted accordingly based on clinical response and hematologic monitoring in patients who are intermediate metabolizers.
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 approximately 2 to 5% of patients (3–5); either is an absolute contraindication to rechallenge. Hepatotoxicity is rarer and can be screened for by blood tests every 6 to 12 months. These medications are associated with increased risk of lymphoma and nonmelanoma skin cancers.
Before starting these medications, patients should have tests to measure the activity of thiopurine methyltransferase (TPMT), an enzyme that converts azathioprine and 6-mercaptopurine to their active metabolites 6-thioguanine (6-TG) and 6-methylmercaptopurine (6-MMP). Patients should also have genotype testing for known low-activity variants of this enzyme. After starting these medications, it is useful to measure levels of 6-TG and 6-MMP to help ensure safe and effective drug dosages. Therapeutic efficacy correlates with 6-TG levels between 230 and 450 picomoles per 8 × 10Before starting these medications, patients should have tests to measure the activity of thiopurine methyltransferase (TPMT), an enzyme that converts azathioprine and 6-mercaptopurine to their active metabolites 6-thioguanine (6-TG) and 6-methylmercaptopurine (6-MMP). Patients should also have genotype testing for known low-activity variants of this enzyme. After starting these medications, it is useful to measure levels of 6-TG and 6-MMP to help ensure safe and effective drug dosages. Therapeutic efficacy correlates with 6-TG levels between 230 and 450 picomoles per 8 × 108 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
Methotrexate is of benefit to many patients with corticosteroid-refractory or corticosteroid-dependent Crohn disease, even those who have not responded to azathioprine or 6-mercaptopurine. Methotrexate is of benefit to many patients with corticosteroid-refractory or corticosteroid-dependent Crohn disease, even those who have not responded to azathioprine or 6-mercaptopurine.
Adverse effects include nausea, vomiting, and asymptomatic liver test abnormalities. Folate 1 mg orally once a day may diminish some of the adverse effects. Both women and men taking methotrexate should ensure the female partner uses a method of contraception that is highly effective (intrauterine device, subdermal contraceptive implant) or effective (oral, vaginal, transdermal, or intramuscular hormonal contraceptive method) (include nausea, vomiting, and asymptomatic liver test abnormalities. Folate 1 mg orally once a day may diminish some of the adverse effects. Both women and men taking methotrexate should ensure the female partner uses a method of contraception that is highly effective (intrauterine device, subdermal contraceptive implant) or effective (oral, vaginal, transdermal, or intramuscular hormonal contraceptive method) (6, 7). Additionally, women and perhaps men should stop methotrexate for at least 3 months before trying to conceive. Monthly complete blood counts and liver tests with albumin should be performed for the first 3 months of therapy then every 8 to 12 weeks during therapy. Alcohol use, hepatitis B and C, obesity, diabetes, and possibly psoriasis are risk factors for hepatotoxicity. Preferably, patients with these conditions should not be treated with methotrexate. Pretreatment liver biopsies are not recommended; liver biopsies are performed if the results of 6 of 12 tests performed in a 1-year period show elevated levels of aspartate aminotransferase (AST). Myelosuppression, pulmonary toxicity, and nephrotoxicity can also occur with methotrexate therapy.). Additionally, women and perhaps men should stop methotrexate for at least 3 months before trying to conceive. Monthly complete blood counts and liver tests with albumin should be performed for the first 3 months of therapy then every 8 to 12 weeks during therapy. Alcohol use, hepatitis B and C, obesity, diabetes, and possibly psoriasis are risk factors for hepatotoxicity. Preferably, patients with these conditions should not be treated with methotrexate. Pretreatment liver biopsies are not recommended; liver biopsies are performed if the results of 6 of 12 tests performed in a 1-year period show elevated levels of aspartate aminotransferase (AST). Myelosuppression, pulmonary toxicity, and nephrotoxicity can also occur with methotrexate therapy.
Cyclosporine and tacrolimus
Cyclosporine,Cyclosporine, which blocks lymphocyte activation, may benefit patients with severe ulcerative colitis unresponsive to glucocorticoids and biologic agents and who may otherwise require colectomy (2). Its only well-documented use in Crohn disease is for patients with refractory fistulas or pyoderma (1). Long-term use (> 6 months) is contraindicated by multiple adverse effects (eg, renal toxicity, seizures, opportunistic infections, hypertension, neuropathy). Generally, patients with severe ulcerative colitis unresponsive to glucocorticoids and biologics are not offered cyclosporine unless there is a reason to avoid the safer curative option of colectomy. If the medication is used, trough blood levels should be kept between 200 to 400 ng/mL (166 to 333 nmol/L) and 6 months) is contraindicated by multiple adverse effects (eg, renal toxicity, seizures, opportunistic infections, hypertension, neuropathy). Generally, patients with severe ulcerative colitis unresponsive to glucocorticoids and biologics are not offered cyclosporine unless there is a reason to avoid the safer curative option of colectomy. If the medication is used, trough blood levels should be kept between 200 to 400 ng/mL (166 to 333 nmol/L) andPneumocystis jirovecii prophylaxis should be considered during the period of concomitant glucocorticoid, cyclosporine, and antimetabolite treatment. prophylaxis should be considered during the period of concomitant glucocorticoid, cyclosporine, and antimetabolite treatment.
Tacrolimus,Tacrolimus, a calcineurin-inhibitor immunosuppressant also used in patients who have had transplants, seems as effective as cyclosporine and may be considered for use in patients with severe or refractory ulcerative colitis who do not require hospitalization (a calcineurin-inhibitor immunosuppressant also used in patients who have had transplants, seems as effective as cyclosporine and may be considered for use in patients with severe or refractory ulcerative colitis who do not require hospitalization (2). The trough blood levels should be kept between 10 to 15 ng/mL (12 to 25 nmol/L). Tacrolimus can be given for short-term treatment of perianal and cutaneous fistulas in Crohn disease.). The trough blood levels should be kept between 10 to 15 ng/mL (12 to 25 nmol/L). Tacrolimus can be given for short-term treatment of perianal and cutaneous fistulas in Crohn disease.
Immunomodulating medications references
1. Lichtenstein GR, Loftus EV, Afzali A, et al. ACG Clinical Guideline: Management of Crohn's Disease in Adults. Am J Gastroenterol. 2025;120(6):1225-1264. Published 2025 Jun 3. doi:10.14309/ajg.0000000000003465
2. Rubin DT, Ananthakrishnan AN, Siegel CA, Barnes EL, Long MD. ACG Clinical Guideline Update: Ulcerative Colitis in Adults. Am J Gastroenterol. 2025;120(6):1187-1224. Published 2025 Jun 3. doi:10.14309/ajg.0000000000003463
3. Weersma RK, Peters FT, Oostenbrug LE, et al. Increased incidence of azathioprine-induced pancreatitis in Crohn's disease compared with other diseases. . Increased incidence of azathioprine-induced pancreatitis in Crohn's disease compared with other diseases.Aliment Pharmacol Ther. 2004;20(8):843-850. doi:10.1111/j.1365-2036.2004.02197.x
4. Wintzell V, Svanström H, Olén O, Melbye M, Ludvigsson JF, Pasternak B. Association between use of azathioprine and risk of acute pancreatitis in children with inflammatory bowel disease: a Swedish-Danish nationwide cohort study. . Association between use of azathioprine and risk of acute pancreatitis in children with inflammatory bowel disease: a Swedish-Danish nationwide cohort study.Lancet Child Adolesc Health. 2019;3(3):158-165. doi:10.1016/S2352-4642(18)30401-2
5. Bermejo F, Lopez-Sanroman A, Taxonera C, et al. Acute pancreatitis in inflammatory bowel disease, with special reference to azathioprine-induced pancreatitis. . Acute pancreatitis in inflammatory bowel disease, with special reference to azathioprine-induced pancreatitis.Aliment Pharmacol Ther. 2008;28(5):623-628. doi:10.1111/j.1365-2036.2008.03746.x
6. Sammaritano LR, Bermas BL, Chakravarty EE, et al. 2020 American College of Rheumatology Guideline for the Management of Reproductive Health in Rheumatic and Musculoskeletal Diseases. Arthritis Care Res (Hoboken). 2020;72(4):461-488. doi:10.1002/acr.24130
7. National Library of Medicine: Daily Med. METHOTREXATE solution. Accessed December 9, 2025. . METHOTREXATE solution. Accessed December 9, 2025.
Biologic Agents
Biologic agents are large (>1 kilodalton), complex molecules produced in living cells.
Anti-TNF medications
Infliximab, certolizumab, adalimumab, and golimumab are antibodies to tumor necrosis factor (TNF). Infliximab, certolizumab, and adalimumab are useful in Crohn disease, particularly in preventing or retarding postoperative recurrence. Infliximab, adalimumab, and golimumab are beneficial in ulcerative colitis for refractory or corticosteroid-dependent disease (Infliximab, certolizumab, adalimumab, and golimumab are antibodies to tumor necrosis factor (TNF). Infliximab, certolizumab, and adalimumab are useful in Crohn disease, particularly in preventing or retarding postoperative recurrence. Infliximab, adalimumab, and golimumab are beneficial in ulcerative colitis for refractory or corticosteroid-dependent disease (1). Patients who are intolerant or have lost their initial response to any one of the aforementioned TNF inhibitors may respond to a different anti-TNF medication.
InfliximabInfliximab is useful for Crohn disease and ulcerative colitis and is given as a single IV infusion 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.
AdalimumabAdalimumab 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 subcutaneously every 2 weeks for three doses and then every 4 weeks for maintenance. The accepted therapeutic serum level is > 20 mcg/mL.
GolimumabGolimumab is beneficial for patients with ulcerative colitis. It is given with an initial loading dose subcutaneously, then at week 2, and then every 4 weeks.
Monotherapy with anti-TNF agents is clearly effective for both induction and maintenance of remission, but some studies suggest better results when anti-TNF agents are initiated in combination with a thiopurine (eg, azathioprine) or methotrexate (Monotherapy with anti-TNF agents is clearly effective for both induction and maintenance of remission, but some studies suggest better results when anti-TNF agents are initiated in combination with a thiopurine (eg, azathioprine) or methotrexate (1). Nevertheless, given the possible increase in adverse effects with combination therapy, treatment recommendations should be individualized. Glucocorticoid tapering may begin after 2 weeks. Adverse effects during infusion (infusion reaction) include immediate hypersensitivity reactions (eg, rash, itching, sometimes anaphylactoid reactions), fever, chills, headache, and nausea. Delayed hypersensitivity reactions have also occurred. Anti-TNF medications given subcutaneously (eg, adalimumab) do not cause infusion reactions, although they may cause local erythema, pain, and itching (injection site reaction). ). Nevertheless, given the possible increase in adverse effects with combination therapy, treatment recommendations should be individualized. Glucocorticoid tapering may begin after 2 weeks. Adverse effects during infusion (infusion reaction) include immediate hypersensitivity reactions (eg, rash, itching, sometimes anaphylactoid reactions), fever, chills, headache, and nausea. Delayed hypersensitivity reactions have also occurred. Anti-TNF medications given subcutaneously (eg, adalimumab) do not cause infusion reactions, although they may cause local erythema, pain, and itching (injection site reaction).
Death from sepsis and other serious infection is a risk of anti-TNF use, so these medications are contraindicated when uncontrolled bacterial infection is present (2). Also, tuberculosis (TB) and hepatitis B reactivation have been attributed to anti-TNF medications (3); 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 (4). 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 medication treatment.
Other biologic agents
Several immunosuppressive interleukins and anti-interleukin antibodies also may decrease the inflammatory response and are being studied for Crohn disease.
VedolizumabVedolizumab and natalizumabnatalizumab are antibodies to leukocyte adhesion molecules. Vedolizumab is used for moderate to severe ulcerative colitis and Crohn disease (are antibodies to leukocyte adhesion molecules. Vedolizumab is used for moderate to severe ulcerative colitis and Crohn disease (1). The recommended dose of IV vedolizumab is administered at 0, 2, and 6 weeks and then every 8 weeks thereafter, or IV vedolizumab is administered at weeks 0 and 2 and then subcutaneously every 2 weeks, starting at week 6. Its effect is believed to be limited to the gut, making it safer than natalizumab, which is used only as a second-line medication through a restricted-prescribing program for the most refractory cases of Crohn disease (). The recommended dose of IV vedolizumab is administered at 0, 2, and 6 weeks and then every 8 weeks thereafter, or IV vedolizumab is administered at weeks 0 and 2 and then subcutaneously every 2 weeks, starting at week 6. Its effect is believed to be limited to the gut, making it safer than natalizumab, which is used only as a second-line medication through a restricted-prescribing program for the most refractory cases of Crohn disease (5, 6). The accepted therapeutic serum level of vedolizumab is > 20 mcg/mL. These medications can cause hypersensitivity reactions and increase the risk of infections. Natalizumab is currently available only through a restricted-use program because it increases the risk of ). The accepted therapeutic serum level of vedolizumab is > 20 mcg/mL. These medications can cause hypersensitivity reactions and increase the risk of infections. Natalizumab is currently available only through a restricted-use program because it increases the risk ofprogressive multifocal leukoencephalopathy (PML). Vedolizumab has a theoretical risk of PML because it is in the same class of medications as natalizumab.(PML). Vedolizumab has a theoretical risk of PML because it is in the same class of medications as natalizumab.
Ustekinumab,Ustekinumab, an anti-IL-12/23 antibody, is used for patients with moderate to severe Crohn disease or ulcerative colitis (1). The initial loading dose is a single IV dose based on weight. After the loading dose, patients are given a maintenance dose 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.
MirikizumabMirikizumab, an anti-IL-23 antibody, is used for patients with moderate to severe Crohn disease or ulcerative colitis (1). Liver enzymes should be performed at baseline and during treatment. Common adverse effects include upper respiratory tract infections (common cold, sore throat, sinusitis), injection site reactions (such as pain, redness, swelling, or rash), headache, arthralgia, rash, herpesvirus infections (eg, cold sores), and elevated liver enzymes.
RisankizumabRisankizumab, an anti-IL-23 antibody, is used for patients with moderate to severe Crohn disease or ulcerative colitis (1). The induction dose is administered at weeks 0, 4, and 8. The maintenance dose is given subcutaneously at week 12 and every 8 weeks thereafter. Using the lowest dose that maintains endoscopic remission is recommended. Liver tests should be performed at baseline and during the induction period.
GuselkumabGuselkumab is a human immunoglobulin G1 lambda monoclonal antibody that binds to the p19 subunit of IL-23 protein and inhibits its binding with cell surface IL-23 receptor. Guselkumab is used for the treatment of adult patients with moderate or severe Crohn disease or ulcerative colitis (is a human immunoglobulin G1 lambda monoclonal antibody that binds to the p19 subunit of IL-23 protein and inhibits its binding with cell surface IL-23 receptor. Guselkumab is used for the treatment of adult patients with moderate or severe Crohn disease or ulcerative colitis (1, 5). It can cause hypersensitivity reactions and increase the risk of infections such as nasopharyngitis, upper respiratory tract infection, and increased liver enzymes.
Biosimilars are biologic medications that are very similar to a reference biologic product. Biosimilars of the anti-TNF medications have been commercialized and used interchangeably with the primary biologic.
Biologic agents references
1. Rubin DT, Ananthakrishnan AN, Siegel CA, Barnes EL, Long MD. ACG Clinical Guideline Update: Ulcerative Colitis in Adults. Am J Gastroenterol. 2025;120(6):1187-1224. Published 2025 Jun 3. doi:10.14309/ajg.0000000000003463
2. Bongartz T, Sutton AJ, Sweeting MJ, Buchan I, Matteson EL, Montori V. Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials. JAMA. 2006;295(19):2275-2285. doi:10.1001/jama.295.19.2275
3. Baddley JW, Cantini F, Goletti D, et al. ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Soluble immune effector molecules [I]: anti-tumor necrosis factor-α agents). Clin Microbiol Infect. 2018;24 Suppl 2:S10-S20. doi:10.1016/j.cmi.2017.12.025
4. Caldera F, Kane S, Long M, Hash JG. AGA Clinical Practice Update on Noncolorectal Cancer Screening and Vaccinations in Patients With Inflammatory Bowel Disease: Expert Review. Clin Gastroenterol Hepatol. 2025;23(5):695-706. doi:10.1016/j.cgh.2024.12.011
5. Lichtenstein GR, Loftus EV, Afzali A, et al. ACG Clinical Guideline: Management of Crohn's Disease in Adults. Am J Gastroenterol. 2025;120(6):1225-1264. Published 2025 Jun 3. doi:10.14309/ajg.0000000000003465
6. National Library of Medicine: Daily Med. TYSABRI-natalizumab injection. Accessed November 18, 2025. . TYSABRI-natalizumab injection. Accessed November 18, 2025.
Small Molecules
Small molecules are sometimes used in the management of moderate to severe IBD. They are given orally and lack the immunogenicity associated with monoclonal antibodies.
TofacitinibTofacitinib is a small-molecule agent that inhibits Janus kinase 1–3 and is used for adult patients with moderate to severe ulcerative colitis (1). 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.
UpadacitinibUpadacitinib is a small-molecule agent that selectively inhibits Janus kinase 1 used for patients with moderate to severe Crohn disease or ulcerative colitis (1, 2). This inhibits IL-6- and IFN-gamma–related signaling, resulting in less effect on natural killer cell depletion than other small-molecule agents such as tofacitinib. The medication should be discontinued if remission is not achieved. The most common adverse effects are acne vulgaris, folliculitis, upper respiratory tract infection, hypersensitivity, nausea, and abdominal pain. In general, the adverse effects are similar to those of other Janus kinase (JAK) inhibitors (eg, tofacitinib). Hematology toxicity such as lymphopenia, anemia, and neutropenia can occur, in which case the medication must be discontinued. A lipid panel should be checked 12 weeks after initiation of a JAK inhibitor due to the potential to increase low-density lipoprotein. JAK inhibitors must be used with caution in patients at increased risk of gastrointestinal perforation (eg, history of diverticulitis). They should also be avoided in patients who have had a stroke or transient ischemic attack within the last 6 months; in patients with increased risk of major cardiovascular (CV) events, such as heart attack, stroke, or death; and in people ≥ 50 years who have at least 1 heart disease (CV) risk factor, especially if they are a current or past smoker (). This inhibits IL-6- and IFN-gamma–related signaling, resulting in less effect on natural killer cell depletion than other small-molecule agents such as tofacitinib. The medication should be discontinued if remission is not achieved. The most common adverse effects are acne vulgaris, folliculitis, upper respiratory tract infection, hypersensitivity, nausea, and abdominal pain. In general, the adverse effects are similar to those of other Janus kinase (JAK) inhibitors (eg, tofacitinib). Hematology toxicity such as lymphopenia, anemia, and neutropenia can occur, in which case the medication must be discontinued. A lipid panel should be checked 12 weeks after initiation of a JAK inhibitor due to the potential to increase low-density lipoprotein. JAK inhibitors must be used with caution in patients at increased risk of gastrointestinal perforation (eg, history of diverticulitis). They should also be avoided in patients who have had a stroke or transient ischemic attack within the last 6 months; in patients with increased risk of major cardiovascular (CV) events, such as heart attack, stroke, or death; and in people ≥ 50 years who have at least 1 heart disease (CV) risk factor, especially if they are a current or past smoker (3, 4).
OzanimodOzanimod is a sphingosine 1-phosphate (S1P) receptor modulator and is used for adults with moderate to severe active ulcerative colitis (1). Ozanimod is contraindicated in people with myocardial infarction within the last 6 months or other cardiac issues such as unstable angina or heart failure. This medication is also contraindicated in people with the following cardiac conduction system disorders: Mobitz type II second-degree block, third-degree atrioventricular block, sick sinus syndrome, or sinoatrial block unless they have a functioning pacemaker (). Ozanimod is contraindicated in people with myocardial infarction within the last 6 months or other cardiac issues such as unstable angina or heart failure. This medication is also contraindicated in people with the following cardiac conduction system disorders: Mobitz type II second-degree block, third-degree atrioventricular block, sick sinus syndrome, or sinoatrial block unless they have a functioning pacemaker (5). Ozanimod should be avoided in people who have had a stroke or transient ischemic attack within the last 6 months. Ozanimod also should be avoided in people with severe untreated sleep apnea and in people taking a monoamine oxidase inhibitor. Ozanimod can increase the risk of infections, cause bradyarrhythmia, lower the number of lymphocytes, and cause liver injury. ECG and varicella zoster virus antibody testing should be performed before starting treatment with ozanimod. ). Ozanimod should be avoided in people who have had a stroke or transient ischemic attack within the last 6 months. Ozanimod also should be avoided in people with severe untreated sleep apnea and in people taking a monoamine oxidase inhibitor. Ozanimod can increase the risk of infections, cause bradyarrhythmia, lower the number of lymphocytes, and cause liver injury. ECG and varicella zoster virus antibody testing should be performed before starting treatment with ozanimod.
EtrasimodEtrasimod is a selective sphingosine 1-phosphate (S1P) receptor modulator used for the treatment of moderately to severely active ulcerative colitis (1). It works by modifying the immune response, reducing the movement of lymphocytes into inflamed tissue, which helps control inflammation in the gastrointestinal tract. However, due to its mechanism of action, it can cause immunosuppresion, thereby increasing the risk of infections, some of which can be serious. Etrasimod can cause leukopenia (lowers the number of white blood cells), which usually resolves within 4 to 5 weeks after stopping the medication The medication is contraindicated in patients with a history of myocardial infarction, unstable angina pectoris, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization, or class III or IV heart failure,history or presence of Mobitz type II second-degree or third-degree atrioventricular block, sick sinus syndrome, or sinoatrial block, unless the patient has a functioning pacemaker (). It works by modifying the immune response, reducing the movement of lymphocytes into inflamed tissue, which helps control inflammation in the gastrointestinal tract. However, due to its mechanism of action, it can cause immunosuppresion, thereby increasing the risk of infections, some of which can be serious. Etrasimod can cause leukopenia (lowers the number of white blood cells), which usually resolves within 4 to 5 weeks after stopping the medication The medication is contraindicated in patients with a history of myocardial infarction, unstable angina pectoris, stroke, transient ischemic attack, decompensated heart failure requiring hospitalization, or class III or IV heart failure,history or presence of Mobitz type II second-degree or third-degree atrioventricular block, sick sinus syndrome, or sinoatrial block, unless the patient has a functioning pacemaker (6).
Small molecules references
1. Rubin DT, Ananthakrishnan AN, Siegel CA, Barnes EL, Long MD. ACG Clinical Guideline Update: Ulcerative Colitis in Adults. Am J Gastroenterol. 2025;120(6):1187-1224. Published 2025 Jun 3. doi:10.14309/ajg.0000000000003463
2. Lichtenstein GR, Loftus EV, Afzali A, et al. ACG Clinical Guideline: Management of Crohn's Disease in Adults. Am J Gastroenterol. 2025;120(6):1225-1264. Published 2025 Jun 3. doi:10.14309/ajg.0000000000003465
3. Zhong X, Luo J, Huang Y, Wang S, Huang Y. Cardiovascular safety of Janus kinase inhibitors: A pharmacovigilance study from 2012-2023. PLoS One. 2025;20(5):e0322849. Published 2025 May 12. doi:10.1371/journal.pone.0322849
4. National Library of Medicine: Daily Med. RINVOQ- upadacitinib tablet, extended release RINVOQ- upadacitinib solution. Accessed November 18, 2025. . RINVOQ- upadacitinib tablet, extended release RINVOQ- upadacitinib solution. Accessed November 18, 2025.
5. National Library of Medicine: Daily Med. ZEPOSIA-ozanimod hydrochloride capsule ZEPOSIA 7-DAY STARTER PACK- ozanimod hydrochloride kit ZEPOSIA STARTER KIT- ozanimod hydrochloride kit. Accessed November 18, 2025. . ZEPOSIA-ozanimod hydrochloride capsule ZEPOSIA 7-DAY STARTER PACK- ozanimod hydrochloride kit ZEPOSIA STARTER KIT- ozanimod hydrochloride kit. Accessed November 18, 2025.
6. National Library of Medicine: Daily Med. VELSIPITY- etrasimod tablet, film coated. Accessed November 18, 2025. . VELSIPITY- etrasimod tablet, film coated. Accessed November 18, 2025.
Antibiotics and Probiotics
Antibiotics
Antibiotics may be helpful in Crohn disease, particularly for fistulizing disease and in combination with infliximab, but they are of limited use in ulcerative colitis, except in Antibiotics may be helpful in Crohn disease, particularly for fistulizing disease and in combination with infliximab, but they are of limited use in ulcerative colitis, except intoxic colitis (1, 2). Metronidazole 500 to 750 mg orally 2 to 3 times a day for 4 to 8 weeks may control mild Crohn disease and help heal fistulas. However, adverse effects (particularly neurotoxicity) often preclude completion of treatment. Ciprofloxacin 500 to 750 mg orally 2 times a day may prove less toxic. Many experts recommend metronidazole and ciprofloxacin in combination. Rifaximin, a nonabsorbable antibiotic may also be beneficial as treatment for active Crohn disease, but there is insufficient evidence to support its routine use (). Metronidazole 500 to 750 mg orally 2 to 3 times a day for 4 to 8 weeks may control mild Crohn disease and help heal fistulas. However, adverse effects (particularly neurotoxicity) often preclude completion of treatment. Ciprofloxacin 500 to 750 mg orally 2 times a day may prove less toxic. Many experts recommend metronidazole and ciprofloxacin in combination. Rifaximin, a nonabsorbable antibiotic may also be beneficial as treatment for active Crohn disease, but there is insufficient evidence to support its routine use (3).
Probiotics
Various nonpathogenic microorganisms (eg, commensal Escherichia coli, LactobacillusLactobacillus species, Saccharomyces) given daily serve as probiotics and may be effective in preventing pouchitis, but other therapeutic roles have yet to be clearly defined (4, 5).
Antibiotics and probiotics references
1. Lichtenstein GR, Loftus EV, Afzali A, et al. ACG Clinical Guideline: Management of Crohn's Disease in Adults. Am J Gastroenterol. 2025;120(6):1225-1264. Published 2025 Jun 3. doi:10.14309/ajg.0000000000003465
2. Rubin DT, Ananthakrishnan AN, Siegel CA, Barnes EL, Long MD. ACG Clinical Guideline Update: Ulcerative Colitis in Adults. Am J Gastroenterol. 2025;120(6):1187-1224. Published 2025 Jun 3. doi:10.14309/ajg.0000000000003463
3. Prantera C, Scribano ML. Rifaximin and Crohn's disease. . Rifaximin and Crohn's disease.World J Gastroenterol. 2013;19(42):7487-7488. doi:10.3748/wjg.v19.i42.7487
4. Barnes EL, Agrawal M, Syal G, et al. AGA Clinical Practice Guideline on the Management of Pouchitis and Inflammatory Pouch Disorders. Gastroenterology. 2024;166(1):59-85. doi:10.1053/j.gastro.2023.10.015
5. Summers RW, Elliott DE, Urban JF Jr, Thompson R, Weinstock JV. Trichuris suis therapy in Crohn's disease. Gut. 2005;54(1):87-90. doi:10.1136/gut.2004.041749
Drugs Mentioned In This Article
