Ulcerative colitis

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

acute severe ulcerative colitis (UC)

1st line – hospital admission + intravenous corticosteroid

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1st line –

hospital admission + intravenous corticosteroid

Acute severe UC (ASUC) in adults is defined as ≥6 bloody stools per day with at least one of the following symptoms: temperature >37.8ºC (>100.0ºF), pulse >90 beats per minute, haemoglobin <105 g/L (<10.5 g/dL), erythrocyte sedimentation rate (ESR) >30 mm/h or C-reactive protein (CRP) >30 mg/L.[50][51] CRP ≥12 mg/L has been suggested as a sensitive cut-off for determining UC severity.[33]

These patients should be admitted to hospital for assessment and intensive management.[23][51][53]

Patients presenting with possible ASUC should have urgent inpatient assessment and blood tests (full blood count, CRP, urea and electrolytes, liver function tests, and serum magnesium level), stool culture, Clostridium difficile assay, radiological imaging (abdominal x-ray to evaluate for toxic megacolon), and flexible sigmoidoscopy. Cross-sectional imaging with a computed tomography (CT) scan should be restricted to patients with a suspected extraluminal complication, perforation, and in those newly diagnosed where the distinction between Crohn’s disease and UC may not be apparent on sigmoidoscopy.[23][52]

A high-dose intravenous corticosteroid such as methylprednisolone or hydrocortisone is recommended first line to induce remission in patients with ASUC.[23][51][53]

Primary options

hydrocortisone sodium succinate: 100 mg intravenously every 6 hours

methylprednisolone sodium succinate: 0.75 to 1 mg/kg intravenously once daily, maximum 60-80 mg/day

Plus – supportive measures

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Plus –

supportive measures

Treatment recommended for ALL patients in selected patient group

Patients may be haemodynamically unstable on admission, and need supportive measures such as blood transfusion, fluids, and electrolyte replacement.[51] Prophylactic low molecular weight heparin (LMWH) to prevent venous thromboembolism is recommended.[23][51]

If patients have concomitant Clostridioides difficile infection, treatment should follow the Infectious Disease Society of America Guidelines (or other appropriate guidelines).[54] See Clostridioides difficile-associated disease.

Consider – ciclosporin or infliximab

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Consider –

ciclosporin or infliximab

Additional treatment recommended for SOME patients in selected patient group

If patients do not respond adequately to intravenous corticosteroid treatment within 3 days, rescue therapy with either intravenous infliximab or ciclosporin should be added to the corticosteroid.[23][51][53]

Although evidence indicates a comparable efficacy, the adverse effect profile of ciclosporin is less favourable than infliximab.[55][56]

There is growing interest in accelerated infliximab induction for acute severe (ASUC).[23] The British Society of Gastroenterology recommends that in patients who do not respond to initial intravenous corticosteroids, an intensified dosing regimen of infliximab can be considered in a select group of patients, especially if serum albumin levels are low.[26]

US guidance does not routinely recommend accelerated infliximab induction for patients with ASUC; dose intensification of infliximab can be considered in patients who have a low serum albumin, and only with careful disease monitoring and ongoing assessment.[23][51] These accelerated dose regimens are not detailed here.

Primary options

ciclosporin: 2 mg/kg intravenously once daily

infliximab: 5 mg/kg intravenously given at weeks 0, 2, and 6 initially, followed by 5 mg/kg every 8 weeks

2nd line – surgery

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2nd line –

surgery

Any patients with severe intractable symptoms or intolerable medicine adverse effects should be considered for colectomy.[51][53]

In acute severe UC (ASUC), delay in surgery is associated with an increased risk of surgical complications.[23][53]

The absolute indications for colectomy for patients with ASUC are complications such as toxic megacolon, perforation, uncontrolled severe haematochezia, or multiorgan dysfunction.[23][51][53]

moderate-to-severe disease

1st line – oral corticosteroid

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1st line –

oral corticosteroid

Oral corticosteroids can be used to induce remission in patients with moderate to severely active ulcerative colitis (UC) of any extent and have typically been first-line induction treatments in moderate-to-severe disease.[23][24][53]

In patients with moderately active UC, oral budesonide multi-matrix system (MMX), a locally acting corticosteroid, can be considered before the use of systemic therapy.[23]

Taper dose gradually once remission is induced.

Primary options

prednisolone: 40-60 mg orally once daily

budesonide: 9 mg orally (extended-release/prolonged-release) once daily in the morning

1st line – tumour necrosis factor (TNF)-alpha inhibitor

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1st line –

tumour necrosis factor (TNF)-alpha inhibitor

TNF-alpha inhibitors are a first-line option for the treatment of moderate-to-severe ulcerative colitis (UC). Options include: golimumab, infliximab, and adalimumab.

In patients with moderate-to-severe UC, early use of biological treatment (with or without immunosuppressant therapy) is suggested.[45] Patients with less severe disease may prefer to begin with TNF-alpha inhibitor monotherapy, but this increases the risk of drug antibody formation.[45] Combination treatment with a TNF-alpha inhibitor plus an immunosuppressant (a thiopurine or methotrexate) is suggested rather than biological monotherapy.[45] Monotherapy with a TNF-alpha inhibitor is preferred to monotherapy with a thiopurine.[45]

Golimumab: in adult outpatients with moderate-to-severe UC, the American Gastroenterological Association (AGA) suggests the use of golimumab over no treatment. In patients who are naive to advanced therapies, the AGA suggests using an intermediate-efficacy drug such as golimumab, rather than a lower efficacy drug (such as adalimumab).[45] Golimumab is recommended for inducing and sustaining clinical remission in adult patients with moderate-to-severe active UC who have had an inadequate response to immunosuppressants such as corticosteroids.[23][45] Golimumab has been shown to induce clinical remission and mucosal healing in patients with moderate-to-severe active UC with a similar safety profile to other TNF-alpha inhibitors.[61][62]

Infliximab: in adult outpatients with moderate-to-severe UC, the AGA recommends the use of infliximab over no treatment. In patients who are naive to advanced therapies, the AGA suggests using a higher-efficacy drug such as infliximab, rather than a lower efficacy drug (such as adalimumab).[45] Infliximab should be considered as an alternative to induce and maintain disease remission.[63][64] When infliximab is used as induction therapy for patients with moderate to severely active UC, combination therapy with azathioprine is recommended.[23][51]

Adalimumab: suggested by the AGA in moderate-to-severe UC over no treatment.[45]

TNF-alpha inhibitors have been associated with a risk of serious infections and malignancy.

Therapeutic drug monitoring (TDM) is becoming more frequently used to check drug trough concentration, and assess for the presence of antidrug antibodies.[92][93][94] BMJ Rapid Recommendations: proactive therapeutic drug monitoring of biologic drugs in adult patients with inflammatory bowel disease, inflammatory arthritis, or psoriasis: a clinical practice guideline Opens in new window TDM can be performed at any point during therapy, and is conditionally recommended by the AGA to guide treatment changes for patients with inflammatory bowel disease.[92][95]

Primary options

infliximab: 5 mg/kg intravenously at weeks 0, 2, and 6 initially, followed by 5 mg/kg every 8 weeks

golimumab: 200 mg subcutaneously at week 0, followed by 100 mg at week 2, then 100 mg every 4 weeks

Secondary options

adalimumab: 160 mg subcutaneously on day 1, followed by 80 mg on day 15, then 40 mg every 2 weeks (starting on day 29)

Consider – immunosuppressant

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Consider –

immunosuppressant

Additional treatment recommended for SOME patients in selected patient group

Combination treatment with a tumour necrosis factor (TNF)-alpha inhibitor plus a thiopurine (e.g., azathioprine, mercaptopurine) or methotrexate is suggested rather than biological monotherapy.[45] Immunosuppressant monotherapy is not recommended for induction therapy.[23][45]

When infliximab is used as induction therapy, it should be given in combination with azathioprine.[23][51]

Thiopurines are associated with a small but statistically significant risk increase for lymphoma among adults with inflammatory bowel disease compared with patients not receiving a thiopurine.[77] Persistent use of a thiopurine is associated with an increased risk of non-melanoma skin cancer; therefore, patients should be educated in primary skin cancer prevention (e.g., reduced ultraviolet exposure).[78] Azathioprine and mercaptopurine doses should be lowered in patients with heterozygous thiopurine methyltransferase variant genotype.[79] Allopurinol should be avoided (or patients monitored closely) in patients taking thiopurines, as it inhibits the breakdown of azathioprine and increases the risk of myelosuppression.[80] However, adjunctive treatment with low-dose allopurinol, in addition to a 25% to 50% thiopurine dose reduction, is required for select patients in whom thiopurine is preferentially metabolised via the hepatotoxic methylmercaptopurine pathway.[81][82][83]

Dose-dependent adverse effects of methotrexate include bone marrow suppression, particularly leukopenia, which can develop suddenly and have an unpredictable course; liver injury; and infections.[76] Other adverse effects (not dose-dependent) include pancreatitis, headache, fatigue, anorexia, weight loss, stomatitis, alopecia, arthralgia, muscular weakness, and rash.[76]

Primary options

azathioprine: 50 mg orally once daily initially, increase gradually according to response, maximum 2.5 mg/kg/day

mercaptopurine: 50 mg orally once daily initially, increase gradually according to response, maximum 1.5 mg/kg/day

methotrexate: consult specialist for guidance on dose

1st line – vedolizumab

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1st line –

vedolizumab

Vedolizumab, a monoclonal antibody against alpha-4-beta-7 integrin (selective adhesion-molecule inhibitor), is a first-line option for the treatment of moderate-to-severe ulcerative colitis (UC).

In patients with moderate-to-severe UC, early use of biological treatment with or without immunosuppressant therapy is suggested.[45]

The American Gastroenterological Association (AGA) recommends vedolizumab in adult outpatients with moderate-to-severe UC over no treatment. In patients who are naive to advanced therapies, the AGA suggests using a higher-efficacy drug such as vedolizumab, rather than a lower efficacy drug (such as adalimumab).

The ACG recommends vedolizumab for induction of remission for patients who have previously failed tumour necrosis factor (TNF)-alpha inhibitor therapy.[23]

Vedolizumab has been shown to be more effective than placebo as induction and maintenance therapy for UC.[66][67] One Cochrane review found vedolizumab to be more effective than placebo for inducing clinical remission, clinical response, and endoscopic remission in patients with moderate-to-severe active UC, and for preventing relapse in patients with quiescent UC.[68] In another systematic review and meta-analysis, vedolizumab efficacy for the induction and maintenance of mucosal healing in UC was similar to that of TNF-alpha inhibitors.[69] Network meta-analysis suggested that vedolizumab may lead to a more sustained clinical response than other biological agents approved for UC.[70] Vedolizumab appears to have a favourable safety profile.[71]

Primary options

vedolizumab: 300 mg intravenously at weeks 0, 2, and 6 initially, followed by 300 mg every 8 weeks

Consider – immunosuppressant

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Consider –

immunosuppressant

Additional treatment recommended for SOME patients in selected patient group

Combination treatment with vedolizumab plus a thiopurine (e.g., azathioprine, mercaptopurine) or methotrexate is suggested rather than biological monotherapy.[45] Immunosuppressant monotherapy is not recommended for induction therapy.[23][45]

Primary options

azathioprine: 50 mg orally once daily initially, increase gradually according to response, maximum 2.5 mg/kg/day

mercaptopurine: 50 mg orally once daily initially, increase gradually according to response, maximum 1.5 mg/kg/day

methotrexate: consult specialist for guidance on dose

1st line – ustekinumab

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1st line –

ustekinumab

Ustekinumab, an interleukin (IL)-12//23 inhibitor, is a first-line option for the treatment of moderate-to-severe ulcerative colitis (UC).

In patients with moderate-to-severe UC, early use of biological treatment with or without immunosuppressant therapy is suggested.[45]

The American Gastroenterological Association (AGA) recommends ustekinumab in adult outpatients with moderate-to-severe UC over no treatment. In patients who are naive to advanced therapies, the AGA suggests using an intermediate-efficacy drug such as ustekinumab, rather than a lower efficacy drug (such as adalimumab). The AGA also suggests using a higher efficacy drug, such as ustekinumab, in patients who have previously been exposed to one or more advanced therapies, particularly tumour necrosis factor (TNF)-alpha inhibitors (infliximab), rather than a lower efficacy drug (such as adalimumab, vedolizumab, ozanimod, and etrasimod).[45]

The interim results of one phase 3 study (UNIFI trial) of ustekinumab in biological-naive and biological-experienced adults with moderate to severely active UC reported that ustekinumab is more effective than placebo for inducing and maintaining remission. In addition, significantly more patients treated with ustekinumab achieved endoscopic improvement and mucosal healing.[72][73]

Primary options

ustekinumab: ≤55 kg body weight: 260 mg intravenously as a single dose, followed by 90 mg subcutaneously every 8 weeks (starting 8 weeks after induction dose); 55-85 kg body weight: 390 mg intravenously as a single dose, followed by 90 mg subcutaneously every 8 weeks (starting 8 weeks after induction dose); >85 kg body weight: 520 mg intravenously as a single dose, followed by 90 mg subcutaneously every 8 weeks (starting 8 weeks after induction dose)

Consider – immunosuppressant

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Consider –

immunosuppressant

Additional treatment recommended for SOME patients in selected patient group

Combination treatment with ustekinumab plus a thiopurine (e.g., azathioprine, mercaptopurine) or methotrexate is suggested rather than biological monotherapy.[45] Immunosuppressant monotherapy is not recommended for induction therapy.[23][45]

Primary options

azathioprine: 50 mg orally once daily initially, increase gradually according to response, maximum 2.5 mg/kg/day

mercaptopurine: 50 mg orally once daily initially, increase gradually according to response, maximum 1.5 mg/kg/day

methotrexate: consult specialist for guidance on dose

1st line – interleukin (IL)-23 inhibitor

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1st line –

interleukin (IL)-23 inhibitor

IL-23 inhibitors are a first-line option for the treatment of moderate-to-severe ulcerative colitis (UC). Options include: mirikizumab, guselkumab, and risankizumab.

In patients with moderate-to-severe UC, early use of biological treatment with or without immunosuppressant therapy is suggested.[45]

In adult outpatients with moderate-to-severe UC, the American Gastroenterological Association (AGA) recommends the use of guselkumab or risankizumab, and suggests the use of mirikizumab, over no treatment. In patients who are naive to advanced therapies, the AGA suggests using an intermediate efficacy drug (mirikizumab) or higher efficacy drug (guselkumab or risankizumab), rather than a lower-efficacy drug (such as adalimumab). In patients who have previously been exposed to one or more advanced therapies, particularly tumour necrosis factor (TNF)-alpha inhibitors, the AGA also suggests using an intermediate efficacy drug (mirikizumab, guselkumab, and risankizumab) rather than a lower-efficacy drug (such as adalimumab, vedolizumab, ozanimod, and etrasimod).[45]

Mirikizumab: in two phase 3, randomised, double-blind, placebo controlled trials it was found that mirikizumab was more effective than placebo in inducing and maintaining clinical remission in patients with moderately to severely active UC.[58]

Guselkumab: in a phase 3, double blind, randomised, placebo-controlled induction and maintenance study, guselkumab was found to be effective and safe compared to placebo as induction and maintenance therapy.[74]

Risankizumab: in two phase 3 randomised controlled trials, risankizumab improved clinical remission rates in an induction trial and in a maintenance trial for patients with moderately to severely active ulcerative colitis, compared with placebo.[75]

Primary options

mirikizumab: 300 mg intravenously at weeks 0, 4, and 8 initially, followed by 200 mg subcutaneously every 4 weeks (starting at week 12)

guselkumab: 200 mg intravenously or 400 mg subcutaneously at weeks 0, 4, and 8 initially, followed by 100 mg subcutaneously every 8 weeks (starting 8 weeks after last induction dose) or 200 mg subcutaneously every 4 weeks (starting 4 weeks after last induction dose)

risankizumab: 1200 mg intravenously at weeks 0, 4, and 8 initially, followed by 180 mg or 360 mg subcutaneously every 8 weeks (starting 4 weeks after last induction dose)

2nd line – sphingosine 1-phosphate (S1P) receptor modulator

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2nd line –

sphingosine 1-phosphate (S1P) receptor modulator

S1P receptor modulators are a second-line option for the treatment of moderate-to-severe ulcerative colitis (UC). Options include: ozanimod and etrasimod.

In adult outpatients with moderate-to-severe UC, the American Gastroenterological Association (AGA) recommends the use of ozanimod or etrasimod over no treatment.[45]

In adult outpatients with moderate-to-severe UC who are naive to advanced therapies, the AGA suggests using a higher efficacy drug, such as ozanimod or etrasimod, rather than a lower efficacy drug (such as adalimumab).[45]

S1P receptor modulators are contraindicated in patients with recent (in the last 6 months) myocardial infarction, unstable angina, stroke, transient ischaemic attack, or heart failure.[25] They are also contraindicated in patients with a history or presence of second- or third-degree atrioventricular block, sick sinus syndrome, or sino-atrial block (unless the patient has a functioning pacemaker).[91]

In the UK, NICE recommends ozanimod for treating moderately to severely active UC in adults, only if conventional treatment cannot be tolerated or is not working well enough and infliximab is not suitable, or biological treatment cannot be tolerated or is not working well enough.[57] NICE recommends etrasimod for treating moderately to severely active UC in patients aged ≥16 years when conventional or biological treatments cannot be tolerated, or the condition has not responded well enough, or lost response to treatment.[101]

Primary options

ozanimod: 0.23 mg orally once daily for 4 days, followed by 0.46 mg once daily for 3 days, then 0.92 mg once daily thereafter

etrasimod: 2 mg orally once daily

2nd line – Janus kinase (JAK) inhibitor

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2nd line –

Janus kinase (JAK) inhibitor

JAK inhibitors are a second-line option for the treatment of moderate-to-severe ulcerative colitis (UC). Options include: tofacitinib and upadacitinib.

In adult outpatients with moderate-to-severe UC, the American Gastroenterological Association (AGA) recommends the use of tofacitinib or upadacitinib over no treatment.[45]

In patients who are naive to advanced therapies, the AGA suggests using an intermediate-efficacy drug (tofacitinib), or a higher-efficacy drug (upadacitinib), rather than a lower efficacy drug. However, JAK inhibitors have restricted use in advanced therapy-naive patients. The prescribing information recommends the use of JAK inhibitors in patients with prior failure or intolerance to tumour necrosis factor (TNF)-alpha inhibitors.[45]

In patients who have previously been exposed to one or more advanced therapies, particularly TNF-alpha inhibitors, the AGA suggests using a higher-efficacy drug, such as tofacitinib or upadacitinib.[45]

Guidelines recommend tofacitinib or upadacitinib for induction of remission in patients with moderate-to-severe UC who have previously been exposed to infliximab, particularly those with primary non-response, or those who are intolerant to TNF-alpha inhibitors.[23][45]

Data from three phase 3 randomised controlled trial show clinical remission at 8 weeks (primary end point) with upadacitinib (26% and 34%) compared with placebo (5% and 4%, respectively) and at 52 weeks (42% or 52%, depending on the dose of upadacitinib compared with placebo 12%).[84][85] One recent systematic review suggested that upadacitinib was the best performing agent for the induction of clinical remission compared with other biologics and small molecule drugs; however, it was also the worst performing agent in terms of adverse effects.[86]

The US Food and Drug Administration (FDA) has issued a warning about an increased risk of serious cardiovascular events, malignancy, thrombosis, and death with JAK inhibitors.[87] This follows final results from a large randomised safety clinical trial which compared tofacitinib with TNF-alpha inhibitors in patients with rheumatoid arthritis. The study found an increased risk of blood clots and death with the lower dose of tofacitinib (5 mg twice daily); this serious event had previously been reported only with the higher dose (10 mg twice daily - the induction dose for UC) in the preliminary analysis.[88] The FDA advises clinicians to reserve JAK inhibitors for patients who have had an inadequate response or are intolerant to one or more TNF-alpha inhibitors and to consider the patient’s individual benefit-risk profile when deciding to prescribe or continue treatment with these drugs, particularly in patients who are current or past smokers, patients with other cardiovascular risk factors, those who develop a malignancy, and those with a known malignancy (other than a successfully treated non-melanoma skin cancer).[87]

The European Medicines Agency (EMA) also recommends measures to minimise the risk of serious adverse effects with JAK inhibitors in patients who are aged >65 years, patients who are current or past smokers, patients with other cardiovascular risk factors, and patients with other malignancy risk factors. The EMA advises that JAK inhibitors should only be used to treat moderate or severe UC in these patient groups if no suitable treatment alternative is available. In addition the EMA recommends that: JAK inhibitors should be used with caution in patients at high risk of blood clots (other than those listed above); and the dose should be reduced in patients who are at risk of venous thromboembolism, major cardiovascular problems, or cancer, where possible.[89]

The UK Medicines and Healthcare products Regulatory Agency (MHRA) supports these recommendations, and also advises patients taking JAK inhibitors to carry out periodic skin examinations, due to an increased risk of non-melanoma skin cancer associated with these drugs.[90]

Primary options

tofacitinib: induction: 10 mg orally (immediate-release) twice daily or 22 mg orally (extended-release) once daily for at least 8 weeks, then transition to maintenance therapy depending on response, may be continued for a maximum of 16 weeks depending on response; maintenance: 5 mg orally (immediate-release) twice daily or 11 mg orally (extended-release) once daily

upadacitinib: induction: 45 mg orally once daily for 8 weeks, then transition to maintenance therapy depending on response; maintenance: 15-30 mg orally once daily

3rd line – colectomy

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3rd line –

colectomy

Any patients with severe intractable symptoms or intolerable medicine adverse effects should be considered for colectomy.[23][51][53]

One systematic review of outcomes and postoperative complications following colectomy for patients with ulcerative colitis (UC) suggests that early and late complications arise in about one third of patients undergoing surgery for UC.[96] While colorectal surgical procedures are recommended for a specific group of patients, the postoperative complications associated with these procedures should not be underestimated.[96]

mild disease

proctitis

1st line – topical (rectal) aminosalicylate

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1st line –

topical (rectal) aminosalicylate

First-line treatment to induce remission for patients with mildly active ulcerative proctitis is a topical (rectal) aminosalicylate.[7][23][51][53] A rectal aminosalicylate is recommended over a rectal corticosteroid.[23][51]

Mesalazine is the only aminosalicylate available as a topical formulation.

Primary options

mesalazine rectal: (1 g/application foam enema) 1-2 g/day rectally; (suppository) 0.75 to 1 g/day rectally

left-sided colitis

1st line – oral aminosalicylate plus topical (rectal) aminosalicylate

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1st line –

oral aminosalicylate plus topical (rectal) aminosalicylate

First-line treatment for the induction of remission in patients with left-sided colitis is a rectal aminosalicylate (in preference to a rectal corticosteroid) combined with an oral aminosalicylate.[7][23][51][53]

Aminosalicylates include mesalazine, sulfasalazine, balsalazide, and olsalazine. Mesalazine is the only aminosalicylate available as a topical formulation.

Primary options

mesalazine: oral dose depends on brand used; consult product literature for guidance on dose

balsalazide: 2250 mg orally three times daily

sulfasalazine: 1 g orally every 6-8 hours initially, titrate according to response, usual dose 0.5 g every 6 hours, maximum 6 g/day

-- AND --

mesalazine rectal: (1 g/application foam enema) 1-2 g/day rectally; (suppository) 0.75 to 1 g/day rectally

Secondary options

olsalazine: 500 mg orally twice daily

and

mesalazine rectal: (1 g/application foam enema) 1-2 g/day rectally; (suppository) 0.75 to 1 g/day rectally

Consider – oral budesonide

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Consider –

oral budesonide

Additional treatment recommended for SOME patients in selected patient group

For patients with mildly active left-sided ulcerative colitis (UC) who are intolerant or non-responsive to oral and rectal aminosalicylate, the addition of oral budesonide multi-matrix system (MMX) is recommended for induction of remission.[7][23][51][53]

Second-generation corticosteroids, such as budesonide MMX, are starting to emerge as a primary treatment option in mild-to-moderate UC.[51][97][98] They are associated with significantly fewer corticosteroid-related adverse events than conventional corticosteroids.[99] MMX technology may facilitate adherence by reducing the pill burden.[100]

Primary options

budesonide: 9 mg orally (extended-release/prolonged-release) once daily in the morning

extensive colitis

1st line – oral aminosalicylate

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1st line –

oral aminosalicylate

The American College of Gastroenterology (ACG) suggests that an oral aminosalicylate is the preferred treatment.[23]

Primary options

mesalazine: oral dose depends on brand used; consult product literature for guidance on dose

balsalazide: 2250 mg orally three times daily

sulfasalazine: 1 g orally every 6-8 hours initially, titrate according to response, usual dose 0.5 g every 6 hours, maximum 6 g/day

Secondary options

olsalazine: 500 mg orally twice daily

Consider – oral corticosteroid

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Consider –

oral corticosteroid

Additional treatment recommended for SOME patients in selected patient group

In patients with mild UC refractory to optimised oral and rectal aminosalicylate therapy, the addition of either oral prednisolone or budesonide multi-matrix system (MMX) is recommended as an alternative.[23][51]

Second-generation corticosteroids, such as budesonide MMX, are starting to emerge as a primary treatment option in mild-to-moderate UC.[97][98] They are associated with significantly fewer corticosteroid-related adverse events than conventional corticosteroids.[99] MMX technology may facilitate adherence by reducing the pill burden.[100]

Primary options

prednisolone: 5-60 mg/day orally given as a single dose or in divided doses

budesonide: 9 mg orally (extended-release/prolonged-release) once daily in the morning

ONGOING

disease in remission

acute severe ulcerative colitis

1st line – infliximab or thiopurine

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1st line –

infliximab or thiopurine

The goal of maintenance therapy is to maintain corticosteroid-free clinical and endoscopic remission; systemic corticosteroids are not recommended for maintenance of remission of ulcerative colitis (UC) of any severity.[23][51]

The choice of drug for maintenance therapy depends on the drug used for induction of remission.

Patients with acute severe UC (ASUC) who achieve remission with infliximab treatment should continue treatment with the same agent for maintenance of remission.[23][51]

If patients with ASUC achieve remission with ciclosporin, thiopurines are suggested for maintenance of remission.[23][51]

Thiopurine therapy is associated with a small but statistically significant risk increase of lymphoma among adults with inflammatory bowel disease compared with patients not on thiopurine therapy.[77] There is also an increased risk of non-melanoma skin cancer; therefore, patients should be educated in primary skin cancer prevention (e.g., reduced ultraviolet exposure).[78]

Azathioprine and mercaptopurine doses should be lowered in patients with heterozygous thiopurine methyltransferase variant genotype.[79]

Allopurinol should be avoided (or patients monitored closely) in patients taking thiopurines, as it inhibits the breakdown of azathioprine and increases the risk of myelosuppression.[80] However, adjunctive treatment with low-dose allopurinol, in addition to a 25% to 50% thiopurine dose reduction, is required for select patients in whom thiopurine is preferentially metabolised via the hepatotoxic methylmercaptopurine pathway.[81][82][83]

Induction and maintenance doses are detailed here. However, if a patient has already been started on a particular treatment, continue treatment at the maintenance dose.

Primary options

infliximab: 5 mg/kg intravenously given at weeks 0, 2, and 6 initially, followed by 5 mg/kg every 8 weeks

azathioprine: 50 mg orally once daily initially, increase gradually according to response, maximum 2.5 mg/kg/day

mercaptopurine: 50 mg orally once daily initially, increase gradually according to response, maximum 1.5 mg/kg/day

moderate-to-severe disease

1st line – individualised maintenance therapy

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1st line –

individualised maintenance therapy

Maintenance therapy should be continued with the drug successful in achieving induction, with the important exception that corticosteroids are not recommended for long-term maintenance.[26] It is assumed that if a drug (excluding corticosteroids and ciclosporin) is effective for induction of remission, it will be continued for maintenance of remission unless otherwise specified.[26][45][51]

There are some exceptions and additional considerations to be aware of.

Patients with previous moderate-to-severe ulcerative colitis (UC) who have achieved remission with tumour necrosis factor (TNF)-alpha inhibitors and/or immunosuppressants, or Janus kinase (JAK) inhibitors, should not be given concomitant aminosalicylates for maintenance of remission.[23][45]

For patients with previously moderate-to-severe UC who achieve remission with corticosteroid induction, a thiopurine (e.g., azathioprine, mercaptopurine) is suggested for maintenance of remission in preference to no treatment.[45] Methotrexate monotherapy is not recommended for maintenance of remission.[23][45]

mild disease: proctitis

1st line – topical (rectal) mesalazine

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1st line –

topical (rectal) mesalazine

In patients with mildly active ulcerative proctitis, a rectal aminosalicylate is recommended to maintain remission.[7][23][51][53]

The large majority of patients with mild ulcerative colitis who achieve remission with aminosalicylate therapy continue with aminosalicylate treatment to maintain remission.[23][51]

Primary options

mesalazine rectal: (1 g/application foam enema) 1-2 g/day rectally; (suppository) 0.75 to 1 g/day rectally

2nd line – treatment escalation

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2nd line –

treatment escalation

Patients on maintenance therapy with a high-dose aminosalicylate, who require two or more courses of corticosteroids in 12 months, or who become corticosteroid dependent or refractory, require treatment escalation to a thiopurine, a TNF-alpha inhibitor, vedolizumab, or tofacitinib.[26][51] The treatment choice should be determined by clinical factors and patient preference.[26]

mild disease: left-sided or extensive colitis

1st line – oral aminosalicylate

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1st line –

oral aminosalicylate

In patients with mildly active left-sided or extensive ulcerative colitis, an oral aminosalicylate is recommended to maintain remission.[7][23][51][53]

Primary options

mesalazine: oral dose depends on brand used; consult product literature for guidance on dose

balsalazide: 2250 mg orally three times daily

sulfasalazine: 1 g orally every 6-8 hours initially, titrate according to response, usual dose 0.5 g every 6 hours, maximum 6 g/day

Secondary options

olsalazine: 500 mg orally twice daily

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Ulcerative colitis

Treatment algorithm

acute severe ulcerative colitis (UC)

hospital admission + intravenous corticosteroid

Primary options

supportive measures

ciclosporin or infliximab

Primary options

surgery

moderate-to-severe disease

oral corticosteroid

Primary options

tumour necrosis factor (TNF)-alpha inhibitor

Primary options

Secondary options

immunosuppressant

Primary options

vedolizumab

Primary options

immunosuppressant

Primary options

ustekinumab

Primary options

immunosuppressant

Primary options

interleukin (IL)-23 inhibitor

Primary options

sphingosine 1-phosphate (S1P) receptor modulator

Primary options

Janus kinase (JAK) inhibitor

Primary options

colectomy

mild disease

topical (rectal) aminosalicylate

Primary options

oral aminosalicylate plus topical (rectal) aminosalicylate

Primary options

Secondary options

oral budesonide

Primary options

oral aminosalicylate

Primary options

Secondary options

oral corticosteroid

Primary options

disease in remission

infliximab or thiopurine

Primary options

individualised maintenance therapy

topical (rectal) mesalazine

Primary options

treatment escalation

oral aminosalicylate

Primary options

Secondary options