INTRODUCTION — Ulcerative colitis (UC) is a chronic inflammatory disease of the colon characterized by bloody diarrhea. Biologic agents, including tumor necrosis factor-alpha inhibitors (eg, infliximab) and anti-integrin antibodies (vedolizumab), and small molecules (eg, tofacitinib) are used for treating patients with moderately-to-severely active UC.
Dosing, monitoring, and adverse effects of biologic agents and small molecules for the treatment of UC in adults will be reviewed here. Selecting a specific biologic agent or a small molecule is influenced by the indication, patient preference, patient medical history, clinician preference, availability in individual countries, and insurance coverage/cost. Medical management of UC is discussed separately:
●(See "Medical management of low-risk adult patients with mild to moderate ulcerative colitis".)
●(See "Management of moderate to severe ulcerative colitis in adults".)
●(See "Management of the hospitalized adult patient with severe ulcerative colitis".)
An overview of thiopurine therapy (azathioprine and mercaptopurine) in inflammatory bowel disease (IBD) is discussed separately. (See "Overview of azathioprine and mercaptopurine use in inflammatory bowel disease".)
An overview of budesonide therapy for IBD is discussed separately. (See "Overview of budesonide therapy for adults with inflammatory bowel disease".)
Adjustments to medication regimens for patients with IBD and suspected or known coronavirus disease 19 (COVID-19) are discussed separately. (See "COVID-19: Issues related to gastrointestinal disease in adults", section on 'Inflammatory bowel disease'.)
TUMOR NECROSIS FACTOR INHIBITORS
Pharmacology and use — Infliximab, adalimumab, and golimumab are monoclonal antibodies directed against anti-tumor necrosis factor (TNF)-alpha. The efficacy of TNF agents for treating Crohn disease provided the rationale for clinical trials of infliximab (and other anti-TNF agents) in patients with UC, a disorder in which TNF also has an important role. TNF-alpha is expressed at high levels in the colonic mucosa of patients with UC [1].
The basis for using these agents is that TNF-alpha has several biologic activities that may be directly related to the pathogenesis of IBD and to the dysregulation of the immune system that occurs in patients with IBD. (See "Overview of biologic agents in the rheumatic diseases", section on 'Anticytokine approaches' and "Treatment of Crohn disease in adults: Dosing and monitoring of tumor necrosis factor-alpha inhibitors".)
●Infliximab – Infliximab is a chimeric monoclonal antibody comprised of 75 percent human and 25 percent murine sequences, which has a high specificity for and affinity to TNF-alpha. Infliximab neutralizes the biologic activity of TNF-alpha by inhibiting binding to its receptors. Infliximab is used by most clinicians in combination with azathioprine or 6-mercaptopurine.
●Adalimumab – Adalimumab is a recombinant, fully human monoclonal antibody that binds to TNF-alpha, thereby interfering with binding to TNF-alpha receptor sites and subsequent cytokine-driven inflammatory processes. The humanized construction of adalimumab is presumed to lower the risk of forming anti-drug antibodies compared with infliximab. (See "Tumor necrosis factor-alpha inhibitors: Induction of antibodies, autoantibodies, and autoimmune diseases", section on 'Adalimumab-induced human anti-human antibodies'.)
●Golimumab – Golimumab is a fully human monoclonal antibody that neutralizes TNF-alpha activity. Golimumab has a longer half-life than adalimumab. (See 'Golimumab' below and "Overview of biologic agents in the rheumatic diseases", section on 'Golimumab'.)
Pretreatment screening — Prior to starting a biologic agent, we review each patient's vaccination and exposure history. Ideally, this review should be performed before the start of immunosuppressive therapy, when the likelihood of developing a protective immune response to any needed vaccine is highest and when live vaccines can be given safely. (See "Medical management of low-risk adult patients with mild to moderate ulcerative colitis", section on 'Approach to vaccination'.)
Pretreatment screening includes:
●Hepatitis B surface antigen (HBsAg), hepatitis B surface antibody, and hepatitis B core antibody.
Patients with serologic evidence of hepatitis B virus (HBV) infection (HBsAg-positive or anti-HBc-positive) are at risk for HBV reactivation if they receive immunosuppressive therapy. Prevention, diagnosis, and treatment of HBV reactivation are discussed separately. (See "Hepatitis B virus reactivation associated with immunosuppressive therapy".)
●Hepatitis C virus (HCV) antibody. For patients with HCV antibodies, we obtain HCV RNA. If HCV RNA is detected, we refer the patient to a hepatologist for consideration of treatment. (See "Screening and diagnosis of chronic hepatitis C virus infection" and "Overview of the management of chronic hepatitis C virus infection".)
However, chronic HCV infection is not a contraindication for immunosuppressive therapy [2,3].
●Interferon-gamma release assay such as QuantiFERON-TB Gold In-Tube assay (preferred) or tuberculin skin test.
If the screening test for latent tuberculosis is positive, a chest radiograph is obtained and the patient is referred to an infectious disease specialist for further evaluation.
•(See "Tuberculosis infection (latent tuberculosis) in adults: Approach to diagnosis (screening)".)
●Documenting immunity to varicella (eg, varicella zoster virus IgG, clinician diagnosis of disease). (See "Diagnosis of varicella-zoster virus infection", section on 'Serologic testing'.)
For patients with evidence of immunity who are ≥19 years old, we assess the need for and timing of zoster (shingles) vaccination, and this is discussed separately. (See "Immunizations in autoimmune inflammatory rheumatic disease in adults", section on 'Zoster vaccines'.)
For patients without evidence of immunity, we assess the need for varicella vaccination based on patient age and risk status, and this is discussed separately. (See "Important health maintenance issues for children and adolescents with inflammatory bowel disease", section on 'Immunizations' and "Immunizations in autoimmune inflammatory rheumatic disease in adults".)
●Serologic testing for Epstein-Barr virus (EBV) and cytomegalovirus (CMV). We obtain anti-EBV and anti-CMV antibodies to assess for evidence of prior infection and thus the patient's risk of reactivation [2]. (See "Clinical manifestations and treatment of Epstein-Barr virus infection" and "Overview of diagnostic tests for cytomegalovirus infection".)
Contraindications — Contraindications to the use of anti-TNF therapies (briefly summarized) include the following. (See "Treatment of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults", section on 'Use of TNF inhibitors'.):
●Active, untreated infection
●Latent (untreated) tuberculosis
●Demyelinating disease (eg, multiple sclerosis, optic neuritis)
●Uncontrolled heart failure
●Malignancy
The safety of anti-TNF therapies and risk of recurrent malignancy in patients with a history of malignancy is less well established than in patients without such a history; the available data are discussed in detail separately. (See "Tumor necrosis factor-alpha inhibitors: Risk of malignancy".)
Dosing and administration — This section describes induction and maintenance dosing for infliximab, adalimumab, and golimumab. In addition, options for dose escalation are included for patients with loss of response while on maintenance therapy. The approach to the patient with UC who is not responding to induction anti-TNF therapy is discussed separately. (See "Management of moderate to severe ulcerative colitis in adults" and "Management of the hospitalized adult patient with severe ulcerative colitis".)
Decisions regarding dose adjustments for patients on maintenance therapy who lose response can be guided by therapeutic drug monitoring (table 1). (See 'Therapeutic drug monitoring' below.)
Infliximab — The induction dose of infliximab for treatment of patients with moderately to severely active UC is 5 mg/kg intravenously at zero-, two-, and six- weeks [4,5].
Patients who achieve an adequate response (based on clinical, endoscopic, and laboratory findings) to initial therapy will require repeat infusions of 5 mg/kg, usually every eight weeks, to maintain remission.
Patients who have a disease flare while on maintenance dosing can be managed by escalating the dose [6]. This can be accomplished by either decreasing the dosing interval (eg, from eight weeks to six weeks) or by increasing the dose (eg, from 5 mg/kg to 10 mg/kg). The maximal dose of infliximab is 10 mg/kg every four weeks.
Adalimumab — Induction therapy with adalimumab is given subcutaneously with the following regimen [7]:
●Week zero, initial dose – 160 mg, given over one or two days
●Week two – 80 mg once
●Week four and thereafter – 40 mg every other week (maintenance dose)
We suggest the same induction regimen for patients who are being switched to adalimumab from another anti-TNF agent.
For patients who have a disease flare while on maintenance dosing, the dosing interval can be shortened to every week [8,9].
Golimumab — The recommended induction dose for golimumab is 200 mg subcutaneously at week zero, then 100 mg at week two, followed by weight-based maintenance therapy [10,11]:
●For patients with actual body weight ≥80 kg – 100 mg every four weeks
●For patients with actual body weight <80 kg – 50 mg every four weeks
For patients who have loss of response while on maintenance dosing and who are candidates for dose escalation, options include increasing the maintenance dose to 100 mg every four weeks, irrespective of body weight [12].
Monitoring — In addition to clinical observation, monitoring the response to anti-TNF agents may include therapeutic drug monitoring (checking drug trough levels, anti-drug antibodies) and biomarker levels (C-reactive protein, fecal calprotectin). Time intervals for follow-up colonoscopy to assess for endoscopic remission are discussed separately. (See "Management of moderate to severe ulcerative colitis in adults".)
Therapeutic drug monitoring — Therapeutic drug monitoring involves measuring serum drug trough concentrations and anti-drug antibodies to optimize the use of anti-TNF agents for patients with IBD. Selecting patients for therapeutic drug monitoring and modifying anti-TNF therapy based on monitoring is discussed separately. (See "Treatment of Crohn disease in adults: Dosing and monitoring of tumor necrosis factor-alpha inhibitors", section on 'Therapeutic drug monitoring'.)
The suggested target drug trough concentrations are primarily based on cross-sectional studies of patients on maintenance therapy [13,14]:
●Infliximab: ≥5 mcg/mL
●Adalimumab: ≥7.5 mcg/mL
Biomarkers of inflammation — In addition to therapeutic drug monitoring, obtaining biomarkers of inflammation (eg, fecal calprotectin or lactoferrin, C-reactive protein [CRP]) can help guide therapy to achieve endoscopic and clinical remission in patients with UC [16,17].
●Stool inflammatory markers – Fecal calprotectin can be used to monitor response to anti-TNF therapy in patients with UC, because fecal calprotectin levels correlate with endoscopic disease activity [18-21]. Fecal calprotectin levels are also more accurate than serum inflammatory markers (eg, CRP) for detecting active disease [22]. Calprotectin is a calcium binding protein complex, found in abundance in neutrophilic granulocytes, and fecal calprotectin levels are increased in patients with mucosal inflammation [20]. (See "Approach to the adult with chronic diarrhea in resource-abundant settings", section on 'General laboratory tests'.)
●CRP – A high baseline CRP level that normalizes with treatment has been associated with a higher chance of having a response to infliximab [23,24].
Adverse events — The TNF-alpha inhibitors have multiple potential adverse events that are listed below and discussed in more detail separately [25]. (See "Tumor necrosis factor-alpha inhibitors: An overview of adverse effects".):
●Infection. (See "Risk of mycobacterial infection associated with biologic agents and JAK inhibitors" and "Tumor necrosis factor-alpha inhibitors: Bacterial, viral, and fungal infections".).
●Malignancy. (See "Tumor necrosis factor-alpha inhibitors: Risk of malignancy".).
●Induction of autoimmunity. (See "Tumor necrosis factor-alpha inhibitors: Induction of antibodies, autoantibodies, and autoimmune diseases".)
●Demyelinating disease.
●Worsening or new onset heart failure.
●Injection site reactions.
●Neutropenia.
●Infusion reactions (algorithm 1). (See "Tumor necrosis factor-alpha inhibitors: An overview of adverse effects", section on 'Infusion reactions'.)
●Cutaneous reactions, including psoriasiform lesions.
The risk of combination therapy (ie, anti-TNF agent plus an immunomodulator [eg, azathioprine]) in patients with IBD is discussed separately. (See "Treatment of Crohn disease in adults: Dosing and monitoring of tumor necrosis factor-alpha inhibitors", section on 'Risks with combination therapy'.)
ANTI-INTEGRIN ANTIBODIES
Pharmacology and use — Vedolizumab is a recombinant humanized, monoclonal antibody, developed as a gut-selective anti-integrin specifically targeting alpha-4-beta-7 integrin in the gastrointestinal tract [26]. Integrins are proteins involved in regulating cellular movement including migration of leukocytes to the gut. Vedolizumab is not typically associated with systemic immunosuppression because it interferes with lymphocyte trafficking limited to the gastrointestinal tract.
Vedolizumab is used for the treatment of moderately to severely active UC.
Pretreatment screening — Prior to starting a biologic agent, we review each patient's vaccination and exposure history, as discussed above. (See 'Pretreatment screening' above.)
Dosing and administration — The induction dose of vedolizumab for treatment of patients with moderately to severely active UC is 300 mg intravenously at zero-, two-, and six- weeks then every eight weeks thereafter [27,28].
Patients who achieve an adequate response (based on clinical and endoscopic findings) to initial therapy will require repeat infusions of 300 mg, usually every eight weeks, to maintain remission. For patients who flare while on maintenance therapy, the dose can be escalated by decreasing the vedolizumab dosing interval (ie, 300 mg intravenously every four weeks) [29].
Monitoring — In addition to clinical observation, monitoring the response to vedolizumab may include checking levels of biomarkers (C-reactive protein, fecal calprotectin). Time intervals for follow-up colonoscopy to assess for endoscopic remission are discussed separately. (See 'Biomarkers of inflammation' above and "Management of moderate to severe ulcerative colitis in adults".)
Adverse events — Vedolizumab use is associated with low incidence of serious infection or infusion-related reactions, although mild nasopharyngitis is a common side effect [27,30]. In an analysis of safety data from four trials including 1256 patients with UC, treatment with vedolizumab was not associated with a higher rate of serious infections compared with placebo (2.7 per 100 person-years [95% CI 1.9-3.4] versus 5.0 per 100 person-years [95% CI 0.1-10.0]) [31]. In an analysis of six studies including 2830 patients with IBD, the rate of infusion-related reactions was ≤5 percent, and most were mild or moderate in intensity and rarely resulted in discontinuation of the drug [31].
Data suggest that for patients with UC, the risk of serious infection is lower with vedolizumab compared with other biologic agents. In a study including three population-based cohorts with mean follow-up of 1.1 years, patients with UC had lower risk of serious infection with vedolizumab compared with anti-TNF agents (incidence rate: 17.6 versus 20.4 per 1000 person-years; hazard ratio [HR] 0.68, 95% CI 0.50-0.93) [30].
SMALL MOLECULES
Janus kinase (JAK) inhibitors
Pharmacology and use — The oral JAK inhibitors that are available for treating moderate to severe UC include tofacitinib and upadacitinib. JAK inhibitors decrease signaling by a number of cytokine and growth factor receptors [32,33].
Pretreatment screening — Prior to starting a JAK inhibitor, we review each patient's vaccination and exposure history (as discussed above), and we check total cholesterol and high density lipoprotein levels because tofacitinib is associated with increased cholesterol levels [34-36]. (See 'Pretreatment screening' above.)
Pretreatment screening includes documenting immunity to varicella (eg, varicella zoster virus IgG, clinician diagnosis of disease). (See "Diagnosis of varicella-zoster virus infection", section on 'Serologic testing'.)
For patients with evidence of immunity who are ≥19 years old, we assess the need for and timing of zoster (shingles) vaccination, because tofacitinib is associated with higher rates of herpes zoster infection [37,38]. These issues are discussed separately. (See "Immunizations in autoimmune inflammatory rheumatic disease in adults", section on 'Zoster vaccines' and 'Adverse events' below.)
Contraindications — We do not use JAK inhibitors in patients with active serious infections (eg, tuberculosis) or severe liver impairment. In addition, we do not use tofacitinib in patients with a history of thromboembolic disease (eg, history of pulmonary embolism, deep venous thrombosis) because of concern for increased risk of thromboembolic events and mortality in patients with rheumatoid arthritis treated with tofacitinib [39]. (See 'Dosing and administration' below and "Treatment of rheumatoid arthritis in adults resistant to initial biologic DMARD therapy", section on 'Tofacitinib'.)
However, preliminary data in patients with immune-mediated inflammatory diseases suggested that upadacitinib was not associated with an increased risk of venous thromboembolism or major cardiovascular events [40].
Dosing and administration — We use a tofacitinib induction dose of 5 mg twice daily for eight weeks, followed by a maintenance dose of 5 mg twice daily [32,39,41]. We use an initial induction dose of 5 mg twice daily because safety data have suggested that higher doses of tofacitinib were associated with increased risk of thromboembolism and mortality in patients with rheumatoid arthritis [39]. (See "Treatment of rheumatoid arthritis in adults resistant to initial conventional synthetic (nonbiologic) DMARD therapy", section on 'Tofacitinib'.)
For patients with active UC who do not achieve remission with tofacitinib 5 mg twice daily and who are at low risk for thromboembolism or cardiovascular disease, tofacitinib can be increased to 10 mg twice daily for a maximum of 16 weeks before decreasing the dose to 5 mg twice daily. (See 'Contraindications' above.)
Risk factors for thrombosis or cardiovascular events include history of inherited hypercoagulable disorder, thromboembolism, cardiovascular disease, hyperlipidemia, or malignancy; use of combined estrogen-progestin oral contraceptives or hormone replacement therapy; or patients undergoing major surgery. (See "Overview of the causes of venous thrombosis" and "Overview of established risk factors for cardiovascular disease" and "Combined estrogen-progestin oral contraceptives: Patient selection, counseling, and use".)
We use an upadacitinib induction dose of 45 mg daily for eight weeks, followed by a maintenance dose of 15 mg once daily [42,43]. For selected patients (eg, those who required 16 weeks of induction therapy or those who do not maintain remission with 15 mg once daily), a maintenance dose of 30 mg once daily may be appropriate.
Monitoring — Obtaining biomarkers of inflammation including fecal calprotectin and C-reactive protein can help guide therapy to achieve endoscopic and clinical remission in patients with UC [16]. Time intervals for follow-up colonoscopy to assess for endoscopic remission and monitoring lipid levels are discussed separately. (See "Management of moderate to severe ulcerative colitis in adults", section on 'Janus kinase (JAK) inhibitors' and 'Biomarkers of inflammation' above.)
Adverse events — The relative safety of JAK inhibitors has generally appeared similar to that of biologic agents used for treating UC; however, additional concerns that require attention include risk of herpes zoster infection and thromboembolism [37,38,44,45]. (See "Treatment of rheumatoid arthritis in adults resistant to initial biologic DMARD therapy", section on 'Tofacitinib' and 'Contraindications' above.)
Tofacitinib is associated with higher rates of herpes zoster infection, particularly for patients receiving higher maintenance doses [37,38]. In a study including 592 patients with UC, the incidence rate of herpes zoster was higher for patients on maintenance therapy with tofacitinib 10 mg twice daily versus placebo (6.6 per 100 person-years [95% CI 3.2-12.2] versus 1 per 100 person-years [95% CI 0.0-5.4]) [37]. However, the rate of herpes zoster was not significantly different for patients on tofacitinib 5 mg twice daily versus placebo. (See 'Pretreatment screening' above.)
Sphingosine 1-phosphate (S1P) receptor modulators — Ozanimod is an oral sphingosine-1-phosphate (S1P) receptor modulator for treating adults with moderate to severe UC. (See "Management of moderate to severe ulcerative colitis in adults" and "Overview of disease-modifying therapies for multiple sclerosis".)
●Pretreatment evaluation – Prior to initiating ozanimod, we obtain complete blood count including lymphocyte count, liver biochemical tests, an electrocardiogram to screen for cardiac conduction abnormalities, and ophthalmic evaluation to screen for uveitis or macular edema. Patients should also be tested for antibodies to varicella zoster virus (VZV), and seronegative patients who are not yet immunosuppressed should have VZV vaccination. (See "Immunizations in autoimmune inflammatory rheumatic disease in adults".)
Ozanimod is contraindicated in patients with myocardial infarction, unstable angina, stroke, transient ischemic attack, or heart failure in the last six months. Additional contraindications include patients with Mobitz type II second- or third-degree atrioventricular block, sick sinus syndrome, or sinoatrial block (unless the patient has a functioning pacemaker), and severe untreated sleep apnea. It is also contraindicated for patients taking a monoamine oxidase inhibitor.
●Dosing and administration – Ozanimod is titrated slowly during the first week. We use an initial ozanimod dose of 0.23 mg daily on days 1 through 4, then 0.46 mg once daily on days 5 through 7 [46]. The maintenance dose is 0.92 once daily starting on day 8.
●Adverse effects – In randomized trials including patients with UC, the most commonly reported adverse effects with ozanimod were anemia, nasopharyngitis, and headache [47]. Cardiovascular events were reported infrequently and included hypertension and bradycardia.
PREGNANCY — The use of biologic agents during pregnancy and lactation is discussed elsewhere. (See "Fertility, pregnancy, and nursing in inflammatory bowel disease", section on 'Medications during pregnancy and lactation'.)
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Ulcerative colitis in adults".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Beyond the Basics topics (see "Patient education: Ulcerative colitis (Beyond the Basics)" and "Patient education: Sulfasalazine and the 5-aminosalicylates (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●Tumor necrosis factor (TNF) inhibitors – Tumor necrosis factor (TNF)-alpha inhibitors, including infliximab, adalimumab, and golimumab, are biologic agents used for treating patients with ulcerative colitis. The decision whether to use infliximab, adalimumab, or golimumab in patients requiring anti-TNF therapy is influenced by the indication, patient preference, and availability in individual countries. (See 'Introduction' above.)
•Pretreatment screening – Prior to starting a biologic agent, we review each patient's vaccination and exposure history. Ideally, this review should be performed before the start of immunosuppressive therapy, when the likelihood of developing a protective immune response to any needed vaccine is highest and when live vaccines can be given safely. (See 'Pretreatment screening' above and "Medical management of low-risk adult patients with mild to moderate ulcerative colitis", section on 'Approach to vaccination'.)
•Contraindications – Contraindications to the use of anti-TNF therapies (briefly summarized) include (see 'Contraindications' above and "Treatment of axial spondyloarthritis (ankylosing spondylitis and nonradiographic axial spondyloarthritis) in adults", section on 'Use of TNF inhibitors'):
-Active, uncontrolled infection
-Latent (untreated) tuberculosis
-Demyelinating disease (eg, multiple sclerosis, optic neuritis)
-Uncontrolled heart failure
-Malignancy
The safety of anti-TNF therapies and risk of recurrent malignancy in patients with a history of malignancy is less well established than in patients without such a history; these issues are discussed separately. (See "Tumor necrosis factor-alpha inhibitors: Risk of malignancy".)
•Monitoring – In addition to clinical observation, monitoring the response to anti-TNF agents may include therapeutic drug monitoring (checking drug trough levels, anti-drug antibodies), biomarker levels (eg, fecal calprotectin, C-reactive protein), and colonoscopy with biopsies. (See 'Monitoring' above.)
•Adverse events – Potential adverse events associated with TNF-alpha inhibitors include (see 'Adverse events' above and "Tumor necrosis factor-alpha inhibitors: An overview of adverse effects"):
-Infection
-Malignancy
-Induction of autoimmunity
-Demyelinating disease
-Heart failure
-Injection site reactions
-Infusion reactions
-Neutropenia
-Cutaneous reactions, including psoriasiform lesions
●Anti-integrin antibodies – For treating patients with moderately to severely active UC, vedolizumab is a recombinant humanized, monoclonal antibody, developed as a gut-selective anti-integrin specifically targeting alpha-4-beta-7 integrin in the gastrointestinal tract. Vedolizumab is not typically associated with systemic immunosuppression because it interferes with lymphocyte trafficking limited to the gastrointestinal tract. (See 'Anti-integrin antibodies' above.)
●Small molecules – For treating patients with moderately to severely active UC, tofacitinib and upadacitinib are orally-administered Janus kinase inhibitors that decrease signaling by a number of cytokine and growth factor receptors. Potential adverse events associated with JAK inhibitors include herpes zoster infection and thromboembolism. (See 'Small molecules' above.)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Paul Rutgeerts, MD (deceased), who contributed as a section editor for UpToDate in Gastroenterology.
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