Medication Summary
The goals of pharmacotherapy are to reduce morbidity and to prevent complications. The treatment of ulcerative colitis (UC) relies on initial medical management with corticosteroids and anti-inflammatory agents, such as sulfasalazine, in conjunction with symptomatic treatment with antidiarrheal agents and rehydration.
Newer agents for induction and/or maintenance include tumor necrosis factor (TNF) inhibitors, vedolizumab, tofacitinib, mirikizumab, ustekinumab, etrasimod, and ozanimod.
5-aminosalicylic Acid Derivative
Class Summary
These agents have anti-inflammatory effects. They are used to maintain remission and to induce remission of mild flares of disease.
Sulfasalazine
Sulfasalazine is useful in treating mild-to-moderate ulcerative colitis and maintaining remission. It acts locally in the colon to reduce the inflammatory response and systemically inhibits prostaglandin synthesis.
Balsalazide (Colazal)
Balsalazide is a prodrug that is converted into 5-aminosalicylic acid through bacterial azo reduction. Metabolites of drug may decrease inflammation by blocking the production of arachidonic acid metabolites in colon mucosa.
Mesalamine (Asacol, Pentasa, Lialda, Rowasa, Canasa)
Mesalamine is the drug of choice for maintaining remission. It is useful for the treatment of mild-to-moderate ulcerative colitis. It is better tolerated and has less adverse effects than sulfasalazine. Enema and suppository forms are typically used in patients with distal colitis.
Tumor Necrosis Factor Inhibitors
Class Summary
These agents prevent the endogenous cytokine from binding to the cell surface receptor and exerting biological activity. These agents adversely affect normal immune responses and allow the development of superinfections; reactivation of latent TB has been reported in patients with previous exposure to TB.
Infliximab (Inflectra, Remicade)
Infliximab is a chimeric mouse-human monoclonal antibody to TNF. It binds free and membrane-bound TNF and thus prevents the cytokine from binding to its cell surface receptor and exerting biological activity. Infliximab is indicated for the treatment of moderate-to-severe active ulcerative colitis in patients who have experienced inadequate response to conventional therapy. It has been shown to reduce signs and symptoms, to achieve clinical remission and mucosal healing, and to eliminate corticosteroid use.
Golimumab (Simponi)
Golimumab is a human anti-TNF-alpha monoclonal antibody that blocks the inflammatory activity of TNF-alpha. It is indicated for induction and maintenance treatment of adults with moderate-to-severe ulcerative colitis that is resistant to prior treatment or requires continuous corticosteroid therapy. Following a brief induction dosage regimen, the maintenance dose is given SC once each month.
Adalimumab (Amjevita, Cyltezo, Humira, Hadlima, Hyrimoz, Adalimumab-atto, Adalimumab-adbm, Adalimumab-bwwd, Adalimumab-adaz)
Adalimumab is a recombinant human anti-TNF-alpha IgG1 monoclonal antibody that blocks the inflammatory activity of TNF-alpha. It specifically binds to TNF-alpha and blocks its interaction with p55 and p75 cell surface TNF receptors. It is indicated for inducing and sustaining clinical remission in adult patients with moderately to severely active ulcerative colitis who have had an inadequate response to immunosuppressants such as corticosteroids, azathioprine, or 6-mercaptopurine (6-MP). The FDA approved adalimumab-atto, adalimumab-adbm, adalimumab-adaz, adalimumab-bwwd as biosimilars and not as interchangeable drugs.
Immunosuppressant Agents
Class Summary
These agents regulate the key factors of the immune system. Agents such as tacrolimus and cyclosporine are often effective in bringing steroid-resistant disease under control.
Azathioprine (Imuran)
Azathioprine is effective as a steroid-sparing or steroid-reducing agent and for use in maintenance therapy. Administration is oral. Onset of action can be delayed by up to 3-6 months.
Cyclosporine (Neoral, Sandimmune)
Cyclosporine is effective as a means of avoiding surgery in patients with severe ulcerative colitis refractory to intravenous corticosteroids. It is given as an intravenous infusion, but can be switched to PO qd dose as "bridge" therapy for outpatient use.
6-Mercaptopurine (Purinethol)
6-Mercaptopurine is effective as a steroid-reducing or steroid-sparing agent and for use in maintaining remission. Administration is oral. Onset of action can be delayed by up to 3-6 months.
Tacrolimus (Prograf)
Immunomodulator produced by the bacteria Streptomyces tsukubaensis. Mechanism of action of tacrolimus is similar to cyclosporine. It is effective in bringing steroid-resistant disease under control. Tacrolimus should not be used for long-term therapy, owing to the risk of nephrotoxicity.
Corticosteroids
Class Summary
Corticosteroids decrease inflammation by suppressing the migration of polymorphonuclear leukocytes and reversing increased capillary permeability. They are used for induction of remission in moderate-to-severe active ulcerative colitis. [117] They have no role in maintaining remission; long-term use can cause adverse effects.
Methylprednisolone (Solu-Medrol, Depo-Medrol, Medrol)
Methylprednisolone is administered intravenously in severe cases.
Prednisone (Sterapred)
Given orally, is effective for the treatment of active moderate-to-severe ulcerative colitis.
Hydrocortisone (Cortef, Solu-Cortef, A-Hydrocort)
High dose corticosteroids such as hydrocortisone are used in the treatment of acute, severe ulcerative colitis. Hydrocortisone decreases inflammation by suppressing the migration of polymorphonuclear leukocytes and reversing increased capillary permeability.
Budesonide (Uceris)
Budesonide is a potent glucocorticoid that has poor oral absorption and extensive first-pass metabolism. These properties make it ideal for reducing gastrointestinal inflammation. It is indicated for remission induction of active, mild-to-moderate ulcerative colitis.
Budesonide rectal (Uceris Rectal Foam)
Budesonide rectal is a corticosteroid available as a 20 mg/metered-dose rectal foam. It is indicated for the induction of remission in adults with active mild-to-moderate distal ulcerative colitis extending up to 40 cm from the anal verge.
Alpha 4 Integrin Inhibitors
Class Summary
Integrin inhibitors are emerging as options for moderate-to-severe active IBD in patients who have had an inadequate response with, lost response to, or were intolerant to a TNF blocker or immunomodulator; or had an inadequate response with, were intolerant to, or demonstrated dependence on corticosteroids.
Vedolizumab (Entyvio)
Vedolizumab is a recombinant humanized monoclonal antibody that binds specifically to α4β7 integrin. It blocks the interaction of α4β7 integrin with mucosal addressin cell adhesion molecule-1 (MAdCAM-1) and inhibits the migration of memory T-lymphocytes across the endothelium into inflamed gastrointestinal parenchymal tissue. It is indicated for both ulcerative colitis and Crohn disease.
JAK Inhibitors
Class Summary
Janus kinase (JAK) pathway inhibitors consist of a group of intracellular tyrosine kinases that transmit signals from cytokine or growth factor-receptor interactions on the cellular membrane to influence cellular processes of hematopoiesis and immune cell function. Within the signaling pathway, JAKs phosphorylate and activate signal transducers and activators of transcription (STATs) which modulate intracellular activity including gene expression. Tofacitinib is a JAK inhibitor that modulates the signaling pathway at the point of JAKs, preventing the phosphorylation and activation of STATs.
Tofacitinib (Xeljanz)
Tofacitinib is a JAK inhibitor indicated for adults with moderately to severely active ulcerative colitis. An induction dose for at least 8 weeks is administered orally, followed by a maintenance dose, depending on the patient's therapeutic response.
Gastrointestinal, Interleukin Inhibitors
Class Summary
Interleukin-12 (IL-12) and IL-23 are cytokines that have been implicated as contributing to the inflammation of ulcerative colitis.
Mirikizumab (Omvoh)
Mirikizumab is a humanized IgG4 monoclonal antibody that binds to the p19 subunit of human interleukin 23 (anti-IL23p19). IL-23 is a naturally occurring cytokine that is involved in mucosal inflammation and affects the differentiation, expansion, and survival of T cell subsets, and innate immune cell subsets, which represent sources of proinflammatory cytokines.
Mirikizumab is indicated for moderately to severely active ulcerative colitis in adults.
Ustekinumab (Stelara)
Ustekinumab is a human immunoglobin (Ig) G1-kappa monoclonal antibody that binds to the p40 protein subunit used by IL-12 and IL-23 cytokines. IL-12 and IL-23 are involved in inflammatory and immune responses (eg, natural killer cell activation, CD4+ T-cell differentiation, and activation). This agent is indicated for adults with moderately to severely active ulcerative colitis.
Sphingosine 1-Phosphate Receptor Modulators
Class Summary
The sphingosine 1-phophate (S1P) receptor modulators, etrasimod and ozanimod, bind with high affinity to S1P receptors. These agents block the capacity of lymphocytes to egress from lymph nodes, reducing the number of lymphocytes in the peripheral blood. The mechanism by which S1P receptor modulators exert therapeutic effects in ulcerative colitis is unknown, but it may involve reduction of lymphocyte migration into the intestine.
Ozanimod (Zeposia)
Ozanimod is indicated for treatment of moderately to severely active ulcerative colitis in adults. Binds to S1P receptors 1 and 5.
Etrasimod (Velsipity)
Indicated for adults with moderately to severely active ulcerative colitis. Binds to S1P receptors 1, 4, and 5.
Antimicrobials
Class Summary
In several controlled, trials, antibiotics have not been shown to provide consistent benefits for the treatment of active ulcerative colitis. Thus, they are usually administered on an empiric basis in patients with severe colitis in whom they may help by averting a life-threatening infection. They have been shown to be effective for the treatment of pouchitis after an IPAA procedure
Ciprofloxacin (Cipro)
A fluoroquinolone, ciprofloxacin has activity against pseudomonads, streptococci, MRSA, Staphylococcus epidermidis, and most gram-negative organisms but no activity against anaerobes. Inhibits bacterial DNA synthesis and, consequently, growth.
Metronidazole (Flagyl)
Metronidazole is an imidazole ring–based antibiotic active against various anaerobic bacteria and protozoa. Used in combination with other antimicrobial agents but as monotherapy for C difficile enterocolitis.
Antidiarrheal
Class Summary
These agents are nonabsorbable synthetic opioids that provide symptomatic relief in the treatment of ulcerative colitis. They prolong GI transit time and decrease secretion via peripheral mu-opioid receptors. They reduce visceral nociception via afferent pathway inhibition.
Diphenoxylate hcl/atropine (Lomotil)
This drug combination consists of 2.5 mg of diphenoxylate, which is a constipating meperidine congener, and 0.025 mg of atropine to discourage abuse. The preparation inhibits excessive GI propulsion and motility, but it may exacerbate constipation.
Loperamide (Imodium)
Loperamide, which is available over the counter, acts on intestinal muscles to inhibit peristalsis and to slow intestinal motility. It prolongs the movement of electrolytes and fluid through bowel and increases viscosity and loss of fluids and electrolytes. Loperamide improves stool frequency and consistency, reduces abdominal pain and fecal urgency, and may exacerbate constipation.
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Ulcerative Colitis. Increased postrectal space is a known feature of ulcerative colitis.
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Ulcerative Colitis. Plain abdominal radiograph from a patient with known ulcerative colitis who presented with an acute exacerbation of his symptoms. The image shows thumbprinting in the region of the splenic flexure of the colon.
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Ulcerative Colitis. Double-contrast barium enema study shows pseudopolyposis of the descending colon.
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Ulcerative Colitis. Single-contrast enema study in a patient with known ulcerative colitis in remission shows a benign stricture of the sigmoid colon.
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Ulcerative Colitis. Plain abdominal radiograph in a 26-year-old with a 10-year history of ulcerative colitis shows a long stricture/spasm of the ascending colon/cecum. Note the pseudopolyposis in the descending colon.
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Ulcerative Colitis. Single-contrast enema study in a patient with total colitis shows mucosal ulcers with a variety of shapes, including collar-button ulcers (yellow arrow), in which undermining of the ulcers occurs, and double-tracking ulcers (red arrow), in which the ulcers are longitudinally orientated.
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Ulcerative Colitis. Double-contrast barium enema study shows total colitis. Note the granular mucosa in the cecum/ascending colon and multiple strictures in the transverse and descending colon in a patient with a more than a 20-year history of ulcerative colitis.
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Ulcerative Colitis. Single-contrast barium enema study shows burnt-out ulcerative colitis.
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Ulcerative Colitis. Intravenous urogram in the same patient as in Image 11 shows features of ankylosing spondylitis.
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Ulcerative Colitis. Lateral radiograph of the lumbar spine in the same patient as in Images 10-11 shows a bamboo spine.
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Ulcerative Colitis. Single-contrast barium enema study in a patient with Shigella colitis.
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Ulcerative Colitis. Postevacuation image obtained after a single-contrast barium enema study shows extensive mucosal ulceration resulting from Shigella colitis.
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Ulcerative Colitis. Double-contrast barium enema studies show granular mucosa associated with Campylobacter colitis.
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Ulcerative Colitis. Ulcerative colitis as visualized with a colonoscope.
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Ulcerative Colitis. Inflamed colonic mucosa demonstrating pseudopolyps.
Tables
Ulcerative Colitis |
Crohn Disease |
Only colon involved |
Panintestinal |
Continuous inflammation extending proximally from rectum |
Skip-lesions with intervening normal mucosa |
Inflammation in mucosa and submucosa only |
Transmural inflammation |
|
Perianal lesions |
No granulomas |
Noncaseating granulomas |
Perinuclear ANCA (pANCA) positive |
ASCA positive |
Bleeding (common) |
Bleeding (uncommon) |
Fistulae (rare) |
Fistulae (common) |
ANCA = antineutrophil cytoplasmic antibodies; ASCA = anti– Saccharomyces cerevisiae antibodies. |
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- European Crohn's and Colitis Organisation (2022)
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