Inflammatory bowel disease: drug treatment and surveillance

• Inflammatory bowel disease (IBD) means chronic relapsing inflammation of the gut. Its two main forms are ulcerative colitis, a superficial continuous inflammation starting in the rectum, and Crohn disease, a transmural, patchy, pan-enteric inflammation with a tendency to strictures and fistulas.
• Drugs are chosen by disease severity, extent and phenotype, not by symptoms alone. Most mild to moderate ulcerative colitis starts with 5-aminosalicylates placed where the disease is; Crohn disease usually starts with budesonide for ileal disease or systemic corticosteroids for more extensive disease, followed by a steroid-sparing plan.
• Corticosteroids induce remission but do not maintain it. Their job is to buy time while azathioprine, 6-mercaptopurine, methotrexate or a biologic takes over.
• Moderate to severe disease, and any disease that is steroid-dependent or fistulising, usually needs advanced therapy: anti-TNF agents, vedolizumab, ustekinumab or the newer interleukin-23 blockers, sometimes with thiopurine combination.
• Colonoscopic surveillance is medical prevention, not a one-off test: in long-standing colonic disease it starts by 8 years after diagnosis and continues on risk-stratified intervals, with chromoendoscopy and biopsies hunting for dysplasia.

By the end of this page you should be able to:

1. Place each IBD drug class in its correct role: induction, maintenance, rescue or fistula healing.
2. Write a sensible escalating sequence from proctitis to acute severe ulcerative colitis, and from mild ileal Crohn disease to complicated disease.
3. State the usual adult doses, combinations and cautions for 5-aminosalicylates, corticosteroids, thiopurines and methotrexate, and know which agents are unsafe in pregnancy.
4. Name the advanced therapies by mechanism, and state the screening and vaccination steps that must precede them.
5. Run a surveillance colonoscopy programme in long-standing IBD and explain the low, intermediate and high-risk intervals. ^[2]
6. Adapt all of the above when resources are limited.

This topic treats the drugs and the surveillance of inflammatory bowel disease as one unified procedure. It assumes that you already know what IBD is, how it presents and how it is investigated; those parts are covered in the ulcerative colitis and Crohn disease topics. Here the question is practical: given a patient with a diagnosis, how do you choose the drug, escalate at the right moment, and keep them safe from both the disease and its treatment?

The two large guideline families that direct modern care are the 2025 American College of Gastroenterology (ACG) ulcerative colitis guideline ^[1] and the 2019 British Society of Gastroenterology (BSG) consensus guideline for IBD in adults ^[5]. Where two sources give different figures, both are shown rather than forcing agreement. A 2013 JAMA review on active Crohn disease ^[3] and a 2014 review on preparing patients for anti-TNF therapy ^[4] support the Crohn-specific and safety sections. The 2023 Korean guideline on biologics for Crohn disease is also cited for the advanced-therapy positioning that it summarises ^[6].

The single most common reason to under-treat IBD is waiting for severe symptoms before changing anything. Tissues heal, or do not, ahead of symptoms. Modern guidelines therefore treat to objective targets: symptom control plus mucosal healing (Mayo endoscopic subscore 0 or 1 in ulcerative colitis; endoscopic healing in Crohn disease), tracked with C-reactive protein and faecal calprotectin ^{[1] [3]}.

Common indications for stepping up are:

• Failure to reach endoscopic or biomarker remission after an adequate induction course (8 weeks for 5-aminosalicylates, a full steroid taper for corticosteroids).
• Steroid dependence, defined as inability to wean systemic steroids below 10 mg prednisolone within 3 months without recurrent active disease, or symptomatic relapse of IBD within 3 months of stopping steroids ^[5].
• Steroid refractoriness, that is inability to induce symptomatic remission with systemic steroids ^[5].
• Disease extent that makes relapse likely: extensive or left-sided ulcerative colitis that flares on maintenance, ileal or ileocolonic Crohn disease with poor prognosis features (young age, stricturing or penetrating behaviour, high C-reactive protein, low albumin or haemoglobin) ^[3].
• Extraintestinal manifestations needing a systemic mechanism: arthropathy, skin or eye disease, which favour anti-TNF or anti-interleukin-12/23 strategies ^[1].
• Fistulising or perianal Crohn disease, which should not be managed with steroids.
• Hospitalisation with acute severe colitis or a complication (abscess, obstruction, perforation, massive haemorrhage).

Aminosalicylates (mesalamine, sulfasalazine) are the workhorses for mild to moderate ulcerative colitis. They act topically on the colonic mucosa and are delivered as suppositories, foams, enemas or oral tablets depending on the extent of disease. The rule that matters most is placement: put the drug where the disease is ^[1].

• Proctitis: rectal 5-aminosalicylate 1 g daily by suppository or foam is first line, preferred over rectal corticosteroids ^[1].
• Refractory proctitis: topical tacrolimus or beclomethasone suppositories, or other topical corticosteroids, are conditional options ^[1].
• Left-sided colitis: rectal 5-aminosalicylate enema at least 1 g daily, preferred over rectal steroids, with or without oral 5-aminosalicylate at least 2.0 g daily when response is partial ^[1].
• Extensive or left-sided disease: oral 5-aminosalicylate at least 2.0 g daily ^[1].
• Mild disease of any extent: a low dose (2.0–2.4 g) of 5-aminosalicylate is as effective as 4.8 g, so avoid routine high dosing ^[1].
• Maintenance: rectal mesalamine 1 g daily after proctitis; oral 5-aminosalicylate at least 1.5 g daily for left-sided or extensive disease ^[1].
• Do not swap formulations: if an adequate dose of one 5-aminosalicylate formulation fails, do not simply try another; move to a different drug class. Combining a 5-aminosalicylate with a biologic once advanced therapy has started adds no efficacy ^[1].
• Crohn disease: aminosalicylates are not recommended for Crohn disease. Sulfasalazine may help mild colonic disease, but neither mesalamine nor sulfasalazine maintains remission. Using an agent with no efficacy in Crohn disease risks allowing silent progression to stricture or penetration ^[3].
• Monitoring: renal function should be checked on therapy, because interstitial nephritis is a recognised rare adverse effect of the class ^[3].

Corticosteroids are bridging drugs. They induce remission well, particularly in moderate to severe or extensive disease, but they neither maintain remission nor alter the long-term course. Systemic corticosteroids and budesonide MMX are therefore not maintenance therapies ^{[1] [5]}.

• Ulcerative colitis induction: oral systemic corticosteroids when 5-aminosalicylate has failed; budesonide MMX 9 mg daily for mildly to moderately active disease of any extent not responding to 5-aminosalicylate, especially when systemic steroid exposure should be minimised ^[1].
• Crohn disease induction: systemic corticosteroids are effective for moderate to severe disease; in one review of active Crohn disease, corticosteroids induced remission in 70 to 80 percent of patients ^[3]. Enteric-coated budesonide is preferred for ileal and right-sided colonic disease because first-pass hepatic metabolism limits systemic exposure ^[3]. ^[1]
• Acute severe ulcerative colitis (ASUC): intravenous methylprednisolone 60 mg daily or intravenous hydrocortisone 100 mg 3 to 4 times daily, combined with nil by mouth, intravenous fluids, electrolyte correction, venous thromboembolism prophylaxis, and stopping NSAIDs, opioids and anticholinergics ^[1].
• Practical cautions: use the lowest effective dose for the shortest time; avoid routine co-prescription of 5-aminosalicylate with systemic steroid when advanced therapy is planned; screen and protect bone health, glucose and blood pressure during use ^{[1] [2]}.

Thiopurines (azathioprine, 6-mercaptopurine) and methotrexate are slow-acting maintenance drugs used for moderate to severe or steroid-dependent IBD. They must be started with, not instead of, faster-onset therapy. Methotrexate is used in Crohn disease but is not recommended for maintenance of ulcerative colitis ^{[1] [3]}.

Typical adult dosing, where sources agree ^{[3] [4]}:

• Azathioprine 2 to 3 mg per kilogram per day. ^[3]
• 6-Mercaptopurine 1 to 1.5 mg per kilogram per day. ^[3]
• Methotrexate is given parenterally (intramuscularly or subcutaneously) weekly when used in Crohn disease, with folic acid supplementation; because of teratogenicity it must be stopped before conception according to current consensus.

Safety points:

• Thiopurines are not for induction: they should not be used alone to induce remission in ulcerative colitis or Crohn disease ^[1].
• Test thiopurine methyltransferase (TPMT) where available before starting; monitor full blood count and liver function throughout.
• The class carries a raised risk of lymphoma, skin cancer and infection, particularly in older patients and in young men ^[3].
• Combination with an anti-TNF during induction improves outcomes and reduces immunogenicity in Crohn disease (SONIC data), and the thiopurine can usually be de-escalated later with a better relapse profile than stopping anti-TNF monotherapy ^[3].
• Live vaccines are contraindicated on thiopurines, as they are on biologics ^[4].

Advanced therapy is indicated for moderate to severe disease, steroid dependence, refractoriness to conventional drugs, high-risk phenotypes and fistulas. Drug positioning has shifted from late rescue to early use in selected patients, because first advanced therapy works better than therapy used after several failures ^{[1] [6]}.

By mechanism:

• Anti-TNF agents: infliximab, adalimumab, golimumab (the last is ulcerative colitis only) and certolizumab pegol (Crohn disease only). Infliximab is the preferred anti-TNF in ulcerative colitis ^[1].
• Anti-integrin: vedolizumab (gut-selective alpha-4 beta-7 blockade). It is superior to adalimumab for induction and maintenance of remission in ulcerative colitis and is a good choice when systemic immunosuppression is undesirable ^[1].
• Anti-interleukin-12/23 p40: ustekinumab.
• Anti-interleukin-23 p19: guselkumab, mirikizumab, risankizumab.
• Sphingosine-1-phosphate receptor modulators: ozanimod, etrasimod (oral daily).
• Janus kinase inhibitors: tofacitinib, upadacitinib. These act fast and are oral, but carry cardiovascular, infection and malignancy warnings, and must be avoided in pregnancy.
• Calcineurin inhibitors: cyclosporine and tacrolimus (rescue in acute severe colitis, or topical for refractory proctitis).

Practical rules from the guidelines ^{[1] [6]}:

• In moderate to severe ulcerative colitis, combine infliximab with a thiopurine for induction; other anti-TNF agents can be used alone or with monitoring.
• Primary non-responders (no benefit despite adequate drug levels) usually need a different mechanistic class, not a second drug within the same class.
• Biosimilars of anti-TNF agents and ustekinumab are acceptable and switching should not be delayed.
• Infliximab and cyclosporine are the rescue options in acute severe ulcerative colitis (see below); surgery should not be deferred on account of prior exposure to either ^[1].
• Every advanced therapy requires pre-treatment safety work, described next.

This checklist applies to both IBD types and is one of the parts most often missed in clinical practice ^{[4] [2]}.

• Latent tuberculosis must be screened for and treated. Isoniazid prophylaxis should be started at least 1 month before starting a biologic ^[4].
• Hepatitis B (and usually hepatitis C and HIV) must be screened for before anti-TNF therapy; hepatitis B non-immune patients should be vaccinated, and active hepatitis B should be suppressed before biologics are used ^[4].
• Vaccination status must be updated before starting immunosuppression. All inactivated vaccines are safe; live vaccines (measles-mumps-rubella, varicella, yellow fever, oral typhoid, live intranasal influenza) are contraindicated on immunosuppression, and should be given only after 3 months off therapy and at least 6 weeks before restarting ^{[4] [2]}.
• Pregnancy planning: methotrexate and Janus kinase inhibitors must be stopped before conception; most other IBD drugs (5-aminosalicylates, thiopurines, anti-TNF agents, vedolizumab) are generally continued through pregnancy to keep the disease in remission, which itself is the best determinant of a good outcome ^[3].

Active disease at conception drives worse outcomes (miscarriage, preterm delivery, low birth weight) far more than any drug. Aim for deep remission before conception and keep effective maintenance therapy running through pregnancy. Corticosteroids are reserved for acute flares. Post-partum live vaccines in infants exposed to biologics in utero should be delayed until drug levels have cleared; inactivated vaccines proceed on schedule ^{[2] [3]}.

Acute severe ulcerative colitis is a medical emergency and should be managed in hospital by a team with surgical backup. Rescue therapy is needed when there is no response to intravenous steroids by day 3 ^[1].

After rescue: continue infliximab for maintenance if it achieved remission; use a thiopurine after cyclosporine rescue. Toxic megacolon is managed with nil by mouth, nasogastric decompression, intravenous fluids, broad-spectrum antibiotics, intravenous steroids, stopping anticholinergics and opioids, close monitoring, and surgical consultation; colectomy is indicated for perforation, uncontrolled bleeding, deterioration over 24 to 48 hours, or failure to improve ^[1].

A few cautions deserve emphasis because they cause preventable harm ^{[4] [3]}:

• Moderate to severe heart failure, multiple sclerosis or optic neuritis, a known hypersensitivity, an active malignancy or prior lymphoma, serious active infection and untreated latent tuberculosis are contraindications to anti-TNF therapy.
• Biologics are not interchangeable: primary non-responders need a new mechanism, not a second anti-TNF.
• Steroid dependence and steroid refractoriness are themselves indications to move to steroid-sparing therapy, not to repeat another steroid course.
• Pregnancy: methotrexate and Janus kinase inhibitors are teratogenic or contraindicated; 5-aminosalicylates, thiopurines, anti-TNF agents and vedolizumab are generally continued ^[3].
• Live vaccines must not be given to patients on immunosuppression; MMR and varicella can be given to non-immune patients after 3 months off therapy and at least 6 weeks before restarting ^[4].

The preparatory steps for anti-TNF therapy apply, with small differences, to thiopurines and other immunosuppressants ^[4]:

1. Confirm active inflammation with endoscopy, imaging, faecal calprotectin or C-reactive protein; do not treat symptoms alone.
2. Exclude mimics: irritable bowel syndrome, bacterial gastroenteritis, Clostridioides difficile, cytomegalovirus, bile salt diarrhoea, bacterial overgrowth, drug-induced diarrhoea, cancer.
3. Screen for latent infection: tuberculosis with an interferon-gamma release assay (or tuberculin skin test) plus chest radiograph, plus hepatitis B, and usually hepatitis C and HIV.
4. Update vaccinations before starting; give live vaccines 3 months before, then wait 6 weeks before immunosuppression if they were not given in childhood.
5. Baseline labs: full blood count, creatinine and electrolytes, liver function, C-reactive protein or calprotectin; pregnancy test when relevant.
6. Counsel about benefits, infection and lymphoma risk, the need to report fever or unexplained symptoms, stopping smoking, and adherence to maintenance.

Done well, drug treatment of IBD is not a drug choice but a loop: induce, reassess objectively, maintain what works, and escalate what does not.

1. Induce remission with the appropriate class for the phenotype and severity (5-aminosalicylate placed by extent for mild to moderate ulcerative colitis; budesonide or systemic steroids for corticosteroid-responsive disease; systemic steroids for severe disease; biologic induction for moderate to severe or fistulising disease).
2. Reassess at about 8 weeks for mild to moderate disease, or at day 3 for acute severe colitis ^[1].
3. Judge response objectively: stool frequency and bleeding scores, C-reactive protein, faecal calprotectin and, where feasible, sigmoidoscopy or colonoscopy to a Mayo subscore of 0 or 1 in ulcerative colitis or to endoscopic healing in Crohn disease ^[1].
4. Move to maintenance with the agent that achieved remission; stop corticosteroids entirely.
5. Escalate to a steroid-sparing immunomodulator, biologic or small molecule when remission is not reached, is steroid-dependent, or the phenotype is high-risk.
6. Monitor on treatment: at intervals appropriate to disease activity; endoscopy when escalation or de-escalation is considered.
7. De-escalate cautiously only after sustained remission, and never abruptly stop a thiopurine in a high-risk patient.
8. Record extras: cancer and infection screening, bone density, vaccinations and pregnancy planning travel with every visit ^[2].

• Loss of response to anti-TNF agents: check trough drug levels and anti-drug antibodies before switching; a primary non-responder with adequate levels usually needs a different mechanistic class ^[1].
• Hepatitis B and tuberculosis vigilance continues on therapy, not only before it ^[4].
• Bone health: dual-energy X-ray absorptiometry at diagnosis in those with conventional risk factors, then every 5 years if normal; calcium 1000 to 1500 mg daily, vitamin D, weight-bearing exercise, and treatment of osteopenia or osteoporosis ^[2].
• Vaccination schedule as per the standard age-appropriate programme, preferably before immunosuppression; live vaccines only after 3 months off therapy ^{[2] [4]}.

Disease-related (from chronic colonic inflammation): colorectal cancer, toxic megacolon, perforation, massive haemorrhage; in Crohn disease, stricture, fistula, abscess, malabsorption and growth failure ^[3].

Therapy-related: steroid side effects, bone marrow and liver toxicity with thiopurines, lymphoma and skin cancer with immunosuppression, infection (including reactivation of latent tuberculosis and hepatitis B) and infusion or injection reactions with biologics ^{[3] [4]}.

Drug interaction caution: systemic glucocorticoids and, less commonly, Janus kinase inhibitors can worsen cardiovascular risk, so risk-factor control matters in patients with cardiac disease ^[2].

Chronic colonic inflammation drives the inflammation–dysplasia–carcinoma sequence, so surveillance is a standing part of IBD care, not a single screening event. Extensive ulcerative colitis, or Crohn colitis involving at least one third of the colon, is the phenotype at risk ^[3].

• When to start: screening colonoscopy no later than 8 years after diagnosis, regardless of IBD phenotype; patients with ulcerative colitis plus primary sclerosing cholangitis need annual colonoscopy starting at the time of diagnosis of primary sclerosing cholangitis ^{[2] [3]}.
• Cancer risk: patients with extensive Crohn colitis have approximately 2 to 3 times the general population risk ^[3]. Control of mucosal inflammation may reduce dysplasia risk ^[1].
• Technique: 4-quadrant biopsies every 10 cm (more than 32 biopsies) plus targeted biopsies of abnormal areas, or chromoendoscopy with dilute indigo carmine or methylene blue, which gives a 2 to 3-fold increase in dysplasia detection ^[3].
• Intervals, risk-stratified: low risk (remission with mucosal healing and at least 2 negative surveillance examinations) every 5 years; intermediate risk every 2 to 3 years; high risk (severe histological inflammation, extensive pseudopolyps or concomitant primary sclerosing cholangitis) annually ^[2].

• Most care rests on a careful history and examination, stool testing for infection, a flexible sigmoidoscopy and basic blood tests; a flexible sigmoidoscopy reproduces much of the assessment in ulcerative colitis.
• 5-aminosalicylates, corticosteroids and thiopurines are inexpensive and produce remission in the majority of mild to moderate disease; use the highest tolerated dose of the class that is available.
• Subcutaneous or biosimilar anti-TNF is the most accessible advanced option; vedolizumab and interleukin-23 blockers may be unobtainable.
• Calprotectin can be replaced by symptom scores and C-reactive protein; assess endoscopic response clinically if formal endoscopy is not available.
• Acute severe colitis remains a clinical and plain-radiograph diagnosis: nil by mouth, intravenous fluids, broad-spectrum antibiotics, intravenous corticosteroids and urgent surgical review must proceed without waiting for computed tomography.
• Prioritise surveillance for patients with extensive disease beyond 10 years, primary sclerosing cholangitis, long-standing pseudopolyps and family history; use high-definition white light with as many targeted biopsies as resources allow.

• 5-Aminosalicylates are first line for mild to moderate ulcerative colitis, placed by extent: suppository or foam 1 g daily for proctitis, enema at least 1 g daily plus oral at least 2.0 g daily for left-sided disease, oral at least 2.0 g daily for extensive disease; maintenance is oral at least 1.5 g daily and rectal 1 g daily respectively ^[1].
• Aminosalicylates are not recommended in Crohn disease; only sulfasalazine has modest efficacy in mild colonic disease ^[3].
• Corticosteroids induce but do not maintain remission. Acute severe ulcerative colitis needs intravenous methylprednisolone 60 mg daily or hydrocortisone 100 mg 3 to 4 times daily, and rescue with infliximab or cyclosporine if there is no response by day 3 ^[1].
• Budesonide MMX 9 mg daily is useful for mildly to moderately active ulcerative colitis; enteric-coated budesonide is preferred for ileal Crohn disease ^{[1] [3]}.
• Thiopurines (azathioprine 2 to 3 mg per kilogram per day; 6-mercaptopurine 1 to 1.5 mg per kilogram per day) and methotrexate (parenteral) are slow-acting maintenance agents, used with faster-onset therapy, never alone for induction ^{[3] [4]}.
• Advanced therapy is indicated by severity, steroid dependence, high-risk phenotype or fistula: anti-TNF (infliximab preferred in ulcerative colitis), vedolizumab (superior to adalimumab in ulcerative colitis), ustekinumab, the IL-23 blockers, and the oral S1P modulators and JAK inhibitors ^{[1] [6]}.
• Infliximab for induction in ulcerative colitis should be combined with a thiopurine; biosimilars are acceptable; primary non-responders need a different mechanistic class ^[1].
• Latent tuberculosis must be treated with isoniazid for at least 1 month before starting a biologic; all biologics require hepatitis B screening and updated vaccination ^[4].
• Acute severe colitis: toxic megacolon is a surgical emergency with systemic toxicity; surgery should not be deferred because of prior infliximab or cyclosporine ^[1].
• Surveillance begins by 8 years after diagnosis (annual from diagnosis in primary sclerosing cholangitis) and runs every 1 to 3 years by risk, every 5 years in the lowest risk ^{[2] [3]}.
• Extensive Crohn colitis carries about 2 to 3 times the general population colorectal cancer risk; mucosal healing reduces dysplasia risk ^{[1] [3]}.
• Chromoendoscopy or 4-quadrant biopsies every 10 cm detects dysplasia 2 to 3 times better than inspection alone ^[3].
• Steroid dependence is defined as inability to get below 10 mg prednisolone within 3 months, or relapse within 3 months of stopping ^[5].
• Live vaccines are off-limits on immunosuppression; give them 3 months off therapy and allow 6 weeks before restarting ^[4].

Ulcerative colitis and inflammatory bowel disease overview; Crohn disease; primary sclerosing cholangitis; colorectal cancer; osteoporosis; vaccination and preventive care in IBD; malabsorption and maldigestion.