Inflammatory Bowel Disease

Inflammatory bowel disease (IBD) is an umbrella term for two chronic, relapsing-remitting immune-mediated disorders of the gastrointestinal tract: Crohn's disease (CD) and ulcerative colitis (UC).^[1][2] Ulcerative colitis produces continuous mucosal inflammation confined to the colon, beginning in the rectum and extending proximally to a variable extent; Crohn's disease can affect any segment of the gastrointestinal tract from mouth to anus, characteristically in a patchy, transmural pattern with skip lesions, and it frequently progresses to stricturing or fistulizing complications that UC does not share. Roughly one in ten cases of colonic disease cannot be confidently classified as either subtype at diagnosis and is termed indeterminate colitis. Both diseases follow a relapsing-remitting course driven by dysregulated mucosal immune activation against the gut microbiome in a genetically susceptible host, both carry an increased long-term risk of colorectal cancer, and both cause systemic extraintestinal manifestations well outside the gut. Distinguishing CD from UC matters clinically because the two diseases respond differently to specific drug classes — 5-aminosalicylates are effective maintenance therapy in UC but not in CD — and because surgery is curative in UC but not in CD, where recurrence after bowel resection is the expected course rather than the exception.

Typical presentation

The most frequent presenting symptoms across both diseases are diarrhea, abdominal pain, rectal bleeding, and weight loss. Nocturnal diarrhea that wakes a patient from sleep is a useful discriminator — it points toward organic pathology such as IBD rather than a functional disorder like irritable bowel syndrome. Extraintestinal manifestations are common to both diseases and include peripheral arthritis and arthralgia, sacroiliitis and ankylosing spondylitis, erythema nodosum, pyoderma gangrenosum, aphthous oral ulcers, episcleritis, scleritis, uveitis, primary sclerosing cholangitis, nephrolithiasis, and an increased risk of venous thromboembolism.^[3] In children and adolescents, growth failure and delayed puberty can be the presenting feature, sometimes preceding overt gastrointestinal symptoms.

• Family history of IBD — the single strongest risk factor for either disease.
• Genetic susceptibility variants, including NOD2/CARD15 variants associated with Crohn's disease.
• Cigarette smoking — increases the risk of developing Crohn's disease and worsens its clinical course, including a higher rate of disease recurrence after surgery; by contrast, current smoking is associated with a lower risk of developing ulcerative colitis, and cessation can occasionally coincide with a new UC flare — despite this, smoking cessation remains the correct recommendation for every patient given its overall harms.
• Appendectomy in childhood or early adulthood — associated with a reduced risk of subsequently developing ulcerative colitis.
• NSAID use — can precipitate a new flare in established IBD.
• Prior enteric infection (infectious gastroenteritis).
• Urban residence and a Westernized, industrialized environment and diet.
• Ashkenazi Jewish ancestry.
• Age of onset follows a bimodal distribution, with a primary peak in adolescence and young adulthood and a smaller second peak later in life.

Distinguishing ulcerative colitis from Crohn disease

Roughly 1 in 10 cases of colonic disease cannot be confidently classified by these features and is termed indeterminate colitis. Irritable bowel syndrome (IBS) is the most common functional mimic — nocturnal diarrhea, rectal bleeding, weight loss, fever, and objectively elevated inflammatory markers (CRP, fecal calprotectin) all argue against a diagnosis of IBS and for organic investigation instead.

History

• Character, frequency, and timing of diarrhea and abdominal pain, including whether diarrhea is nocturnal.
• Presence and severity of rectal bleeding and weight loss.
• Extraintestinal symptoms — aphthous ulcers, joint pain, skin lesions, eye symptoms, perianal symptoms, fever.
• Family history of IBD.
• Prior endoscopic or radiologic results, and prior medical (drug, dose, duration) or surgical treatment.
• Smoking history.

Physical examination

• Weight and nutritional status, abdominal tenderness or a palpable mass, and perianal inspection for fistulae or abscess.
• Growth parameters in children — height, weight, and growth curve/Tanner staging.
• Extraintestinal findings — peripheral joints and sacroiliac exam, skin, mouth, and eyes.

Investigations

• CBC, electrolytes, renal function, and liver enzymes/function tests.
• Inflammatory markers — CRP, ESR, albumin, and fecal calprotectin, which correlates with mucosal inflammation and is useful both at diagnosis and for ongoing monitoring.
• Stool studies to exclude an infectious or superimposed cause — C. difficile toxin, stool culture, and ova and parasites — before attributing new or worsening symptoms to an IBD flare.
• Ileocolonoscopy with biopsy is the primary diagnostic investigation; upper endoscopy, capsule endoscopy, or balloon-assisted enteroscopy add yield when small bowel Crohn's disease is suspected.
• Cross-sectional imaging (CT or MR enterography, small bowel ultrasound) to assess disease extent, complications (stricture, abscess, fistula), and small bowel involvement not reachable by colonoscopy.

What is not indicated

Do not perform a full colonoscopy with air insufflation during acute severe colitis — the perforation risk in a friable, acutely inflamed colon outweighs the diagnostic benefit; a limited, unprepped flexible sigmoidoscopy is safer if endoscopic assessment is genuinely needed acutely. Do not attribute a new or worsening symptom in a known IBD patient to a flare without first excluding C. difficile infection, which independently precipitates severe exacerbations, including toxic megacolon.

Disease activity indices

The Harvey-Bradshaw Index (HBI) is a simple bedside index of Crohn's disease activity that requires no laboratory testing.^[4]

Interpretation: fewer than 5 points is remission, 5-7 mild disease, 8-16 moderate disease, and more than 16 severe disease. The HBI suits rapid clinic or telephone follow-up, but three of its five components are graded severity ratings rather than simple present/absent criteria, and the stool-frequency component is an open count rather than a fixed point value — for that reason it is presented here as a teaching table only, not as an interactive point-and-click calculator (see the reasoning documented alongside this chapter's authoring notes).

For ulcerative colitis, the partial Mayo score (the clinic-usable version that excludes the endoscopic subscore, which can only be scored at colonoscopy) is commonly used for activity assessment between endoscopies.^[5]

Interpretation: a partial Mayo score of 2 or less, with no individual domain scored above 1, is consistent with remission; higher scores indicate increasingly active disease. The full Mayo score adds a 0-3 endoscopic subscore (total range 0-12) and is the standard instrument for formally documenting endoscopic remission and mucosal healing, but it cannot be scored without a colonoscopy. Separately, hospitalized patients with severe colitis are assessed against the Truelove and Witts criteria for severe disease — six or more bloody stools per day plus at least one marker of systemic toxicity (fever, tachycardia, anemia, or a markedly elevated ESR) — which determines the need for inpatient IV corticosteroid therapy.

• Induce and then maintain clinical and endoscopic remission — a treat-to-target, tight-control strategy rather than treating symptoms alone.^[6]
• Normalize objective markers of inflammation (CRP, fecal calprotectin) as an intermediate target on the way to confirming endoscopic healing.
• Achieve mucosal healing on endoscopy.
• Minimize corticosteroid exposure — the goal is durable, steroid-free remission, not repeated steroid courses.
• Prevent disease-related complications — strictures, fistulae, and abscesses in Crohn's disease; toxic megacolon and colectomy risk in ulcerative colitis.
• Detect and prevent colorectal cancer through appropriate surveillance.
• Optimize nutritional status and support normal growth and pubertal development in children and adolescents.
• Identify and treat extraintestinal manifestations alongside luminal disease.
• Preserve quality of life, work/school function, and fertility.

• Encourage smoking cessation in every patient — it worsens the course of Crohn's disease specifically, including a higher rate of postoperative recurrence, and carries independent health harms regardless of IBD subtype.
• Advise patients not to arbitrarily restrict food groups; the goal is adequate caloric and nutritional intake, with nutritional supplementation or parenteral nutrition reserved for patients who are malnourished.
• Exclusive enteral nutrition (formula feeding by tube or by mouth, with no other food) is an effective induction therapy for Crohn's disease and is often used first-line in pediatric patients specifically to avoid the growth-impairing effects of corticosteroids; adult adherence is limited by the palatability and tolerability of prolonged formula-only feeding.
• A Crohn's disease exclusion diet combined with partial enteral nutrition is an emerging option with growing evidence; dietary exclusion alone, without an enteral nutrition component, has not been shown to be effective on its own.
• Avoid NSAIDs — they are linked to symptom flares in both diseases.
• Monitor for dehydration and electrolyte abnormalities during flares, particularly in ulcerative colitis.
• Surgery (colectomy) is curative in ulcerative colitis and is used for patients refractory to medical therapy or with precancerous/cancerous colonic changes; an ileoanal pouch reconstruction is commonly performed, and pouchitis — tenesmus, diarrhea, and bleeding after pouch construction — is a recognized, generally antibiotic-responsive complication.
• Surgery in Crohn's disease treats strictures, abscesses, and fistulae, or disease refractory to medical management; because recurrence after resection is expected, conservative surgery that removes the minimum length of bowel is favoured. Preoperative anti-TNF therapy may increase postoperative infectious complications, which should factor into the timing of surgery relative to biologic dosing.
• Psychological support may reduce pain, fatigue, and relapse frequency in adolescents with IBD; evidence in adults is weaker, but distress and quality-of-life impact should still be assessed and addressed at every visit.

Pregnancy

Active, uncontrolled IBD carries real pregnancy risks — preterm birth, low birth weight, and miscarriage — and this risk generally exceeds the risk of continuing most IBD medications; advise patients planning pregnancy to try to conceive during a period of disease remission, and do not stop an effective medication at conception purely because of pregnancy unless that specific drug is contraindicated.^[10]

5-aminosalicylates (mesalazine, sulfasalazine) are considered low risk in pregnancy; patients on sulfasalazine should supplement with 2 mg folic acid daily starting before conception, given its antifolate effect.

Corticosteroids may be used at any stage of pregnancy, including the first trimester, when benefits outweigh risks (for example, during a flare), with a small increased risk of oral clefts reported with first-trimester exposure.

Azathioprine and 6-mercaptopurine are considered low risk in pregnancy despite historically conflicting data.

Contraindicated in pregnancy methotrexate (teratogenic and abortifacient — discontinue 3-6 months before attempted conception, with effective contraception in place), the JAK inhibitors tofacitinib and upadacitinib (teratogenic in animal studies, contraindicated, with a required contraception washout after stopping), and the S1P modulators ozanimod and etrasimod (contraindicated, teratogenic in animal studies, requiring a washout of several months before conception).

Anti-TNF agents (adalimumab, infliximab, golimumab) are considered low risk through the first and second trimesters; because they are actively transported across the placenta in the third trimester and can remain in the infant's circulation for months after birth, live vaccines should be delayed in an infant exposed to a maternal anti-TNF agent late in pregnancy. Data for vedolizumab, ustekinumab, risankizumab, guselkumab, and mirikizumab in pregnancy are more limited, so reserve these for when the potential benefit clearly outweighs the uncertainty.

Breastfeeding

5-aminosalicylates, corticosteroids (including prednisone/prednisolone), and anti-TNF agents are considered compatible with breastfeeding, since anti-TNF antibodies transfer into milk only in low amounts and are broken down in the infant's gut. Azathioprine and 6-mercaptopurine are generally considered compatible, though separating breastfeeding by a few hours from dosing is a reasonable precaution. Cyclosporine, methotrexate, the JAK inhibitors, and the S1P modulators (ozanimod, etrasimod) are not recommended during breastfeeding.

Pediatrics

Growth and pubertal development must be actively monitored — both untreated disease activity and chronic corticosteroid exposure can impair growth, which is why exclusive enteral nutrition is favoured over corticosteroids for inducing remission in pediatric Crohn's disease whenever feasible. Biologic dosing in children is weight-based and differs from adult fixed dosing; confirm pediatric-specific regimens before prescribing. JAK inhibitors and S1P modulators do not have established pediatric IBD dosing in Canada.

Older adults

Corticosteroid-related risks (osteoporosis, infection, delirium) and thiopurine-related risks (myelosuppression, lymphoproliferative disease, nonmelanoma skin cancer) are more consequential in older patients — factor age into the choice between a thiopurine and a biologic/small-molecule maintenance strategy. JAK inhibitors carry a specifically elevated cardiovascular and malignancy signal in patients over 65 with additional cardiovascular risk factors.^[11][12]

Renal and hepatic impairment

Reduce azathioprine/6-mercaptopurine doses in renal impairment given slower clearance of active metabolites. Methotrexate requires dose reduction with reduced creatinine clearance and should be avoided altogether in severe renal impairment. Cyclosporine requires close renal function monitoring given direct nephrotoxicity. Tofacitinib and upadacitinib require dose reduction in moderate-severe renal or hepatic impairment per current product labelling. Oral or rectal budesonide requires cautious, reduced dosing in significant hepatic impairment given its reliance on hepatic first-pass metabolism for its local-activity profile.

Check fecal calprotectin and CRP at diagnosis and with any symptom change — both correlate with mucosal inflammation and help distinguish a true flare from a functional symptom overlay without requiring repeat endoscopy for every decision. Obtain CBC and liver enzymes at baseline and periodically during thiopurine or methotrexate therapy to monitor for myelosuppression and hepatotoxicity; check TPMT or NUDT15 status before starting a thiopurine. Screen for latent tuberculosis (history, chest x-ray, and a tuberculin skin test or interferon-gamma release assay) and hepatitis B and C serologies before starting any anti-TNF agent or other biologic — manage a patient with evidence of latent TB or active hepatitis B in collaboration with infectious diseases before proceeding.^[13] Confirm varicella immunity and complete recommended vaccinations, including inactivated influenza annually and pneumococcal vaccination, before starting immunosuppressive therapy where possible — live vaccines are contraindicated once a patient is immunosuppressed and, if needed, should be given at least 4 weeks before starting therapy or deferred until at least 3 months after immunosuppressive therapy is stopped. Monitor lipids in patients on tofacitinib or upadacitinib. Patients on long-term azathioprine or 6-mercaptopurine should have annual skin checks and be counselled on sun protection, given an increased risk of nonmelanoma skin cancer with cumulative thiopurine exposure. Use therapeutic drug monitoring (trough drug level and antidrug antibody titre) to guide management of secondary loss of response to an anti-TNF agent — a low drug level with a low or absent antibody titre generally favours dose or frequency escalation, while a high antibody titre favours switching agents. Begin colorectal cancer surveillance colonoscopy within 8 years of diagnosis for extensive colitis, left-sided colitis, and Crohn's colitis involving more than one-third of the colon alike — current consensus no longer uses the older, longer 15-year starting point that was once applied specifically to left-sided disease — then repeat every 1-3 years depending on risk factors, or annually starting at diagnosis in any patient with concurrent primary sclerosing cholangitis.^[2] Monitor bone density with any history of repeated or prolonged corticosteroid courses.

1. Confirm true treatment failure before escalating — exclude nonadherence, an incorrect diagnosis, a missed infectious cause (C. difficile, CMV colitis), or a mechanical complication (stricture, abscess) with imaging, since escalating immunosuppression onto an undrained abscess or an unrecognized infection worsens outcomes.
2. Distinguish primary non-response (never responded) from secondary loss of response (responded, then lost effect) to a biologic — secondary loss of response is usually managed with therapeutic drug monitoring to guide dose or frequency escalation, or a switch to a different agent, while primary non-response generally warrants a switch to a different drug class rather than dose escalation within the same class.
3. For a patient with a low or undetectable anti-TNF drug level and a high antidrug antibody titre, switch to a different anti-TNF agent or a different drug class rather than escalating the dose, since ongoing immunogenicity will likely blunt any dose increase too — consider adding or optimizing a concomitant immunomodulator to reduce future immunogenicity.
4. For inadequate response to a first-line advanced therapy without an identifiable mechanical or infectious cause, switch to an agent from a different mechanistic class (for example, anti-TNF to an anti-integrin, an anti-IL-23 agent, a JAK inhibitor, or an S1P modulator) rather than a second agent within the same class.
5. Re-evaluate surgical candidacy at every escalation step, particularly in Crohn's disease with a dominant stricture or fistula (a mechanical problem generally needs a mechanical solution, not more immunosuppression) and in ulcerative colitis after failed medical rescue therapy for acute severe colitis.
6. Reassess and optimize nutritional status at each treatment-failure step — undernutrition itself impairs mucosal healing and surgical outcomes.

• Continuing or repeating corticosteroid courses as a substitute for a proper maintenance strategy — corticosteroids have no maintenance efficacy and only accumulate harm; a patient with recurrent flares needing repeated steroid courses needs their maintenance regimen changed, not another taper.
• Using mesalazine or sulfasalazine for maintenance of Crohn's disease — 5-ASA agents are not effective maintenance therapy for CD, only UC.
• Starting an anti-TNF agent or other biologic without completing tuberculosis and hepatitis B/C screening first.
• Missing a superimposed C. difficile infection in a patient presenting with a “flare” — treat the infection and reassess before escalating immunosuppression.
• Using antidiarrheal agents (loperamide, diphenoxylate/atropine) in a patient with severe or fulminant colitis — these agents slow colonic transit and increase the risk of precipitating toxic megacolon.
• Missing NSAID use as a trigger for a new or worsening flare.
• Stopping a thiopurine or biologic abruptly, or tapering it, without a deliberate, discussed plan — unplanned discontinuation risks a rebound flare and, for anti-TNF agents, an increased risk of immunogenic loss of response if restarted later.
• Missing annual skin checks and sun-protection counselling in patients on long-term thiopurine therapy.
• Giving a live vaccine to a patient who is currently immunosuppressed, or too soon after stopping immunosuppressive therapy.
• Failing to confirm effective contraception before starting methotrexate, a JAK inhibitor, or an S1P modulator, given their pregnancy risk.
• Assuming codeine will control diarrhea or pain equally well in every patient — a genetic polymorphism in CYP2D6 can substantially blunt its conversion to active drug and its clinical effect in some patients.

How to use this table: Doses are adult doses and require patient-specific confirmation (renal/hepatic function, weight, allergy history). Pediatric dosing is weight-based per the current product monograph unless stated. Drug pricing is intentionally omitted. Select any drug name to open its complete Pharmasist Drug Database page.

Drug Class: 5-Aminosalicylic Acid Derivatives

Drug Class: Corticosteroids, systemic (induction only -- never for maintenance)

Drug Class: Corticosteroids, locally-acting (induction only)

Drug Class: Immunomodulators

Drug Class: Anti-TNF-alpha biologics

Drug Class: Anti-integrin and anti-IL-12/23 / anti-IL-23 biologics

Drug Class: JAK inhibitors and S1P receptor modulators

Reserve for biologic-refractory disease. JAK inhibitors carry a class boxed warning for malignancy, major cardiovascular events, and thrombosis, particularly in patients over 65 with additional cardiovascular risk factors.

Drug Class: Antibiotics, antidiarrheals, and adjuncts

Use antidiarrheal agents with caution and avoid them altogether in severe or fulminant colitis, given the risk of precipitating toxic megacolon.