Inflammatory Bowel Disease
Clinical Snapshot
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.
Recognize the Condition
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.
Ulcerative colitis vs Crohn disease presentation
Ulcerative colitis
Continuous mucosal inflammation starting in the rectum and extending proximally to a variable extent, always involving the rectum. Bloody diarrhea with urgency and tenesmus is the dominant symptom. Disease is classified by anatomic extent: ulcerative proctitis (rectum only), proctosigmoiditis (rectum and sigmoid colon), left-sided colitis (to the splenic flexure), and extensive colitis/pancolitis (beyond the splenic flexure, up to and including the entire colon). Fistulae and strictures are uncommon. Colectomy removes the diseased organ and is curative.
Crohn disease
Patchy, transmural (full-thickness) inflammation that can affect any segment from mouth to anus, most often the terminal ileum and proximal colon, with unaffected “skip” areas between involved segments. Abdominal pain and diarrhea (often non-bloody unless colonic) predominate, along with a higher rate of perianal disease — fistulae, abscesses, and fissures. Behaviour is classified as inflammatory, stricturing (fibrostenotic), or penetrating/fistulizing, and more than one pattern can coexist in the same patient. Because inflammation is transmural rather than confined to the mucosa, surgical resection is not curative — recurrence at the anastomosis is the expected course, so conservative, bowel-sparing resection is favoured.
Risk Factors
- 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.
Red Flags & Refer
Refer every new IBD diagnosis to specialist gastroenterology care for confirmation of diagnosis, initial treatment planning, and management of exacerbations — this is not a condition managed on presumptive diagnosis alone. The following findings are emergencies requiring immediate escalation.
- Toxic megacolon — fever, tachycardia, abdominal distension and tenderness, and radiographic colonic dilation in a patient with severe active colitis; most often precipitated by fulminant colitis itself, Clostridioides difficile superinfection, or use of an antimotility, opioid, or anticholinergic drug during active severe disease.
- Bowel perforation — sudden severe abdominal pain, peritoneal signs, or free air on imaging.
- Severe gastrointestinal bleeding or hemodynamic instability.
- Fulminant/acute severe colitis meeting severe criteria (frequent bloody stools with systemic toxicity — fever, tachycardia, anemia, or a markedly elevated inflammatory marker) — requires hospital admission for IV corticosteroids and close surgical involvement, not outpatient management.
- Bowel obstruction from a Crohn's stricture — severe colicky pain, distension, vomiting, and absolute constipation.
- New fever with severe localized abdominal pain or a palpable mass, suggesting an intra-abdominal or perianal abscess.
- Any sign of sepsis.
- Severe dehydration or electrolyte derangement from high-volume diarrhea.
Assessment & Diagnosis
Distinguishing ulcerative colitis from Crohn disease
| Feature | Ulcerative colitis | Crohn disease |
|---|---|---|
| Location | Colon only, always including the rectum | Any segment, mouth to anus — most often terminal ileum and colon |
| Pattern | Continuous | Patchy, with skip lesions |
| Depth of inflammation | Mucosal | Transmural |
| Rectal involvement | Essentially always | Variable, often spared |
| Bleeding | Common, often the dominant symptom | Less common unless colonic |
| Strictures / fistulae / perianal disease | Rare | Common |
| Granulomas on biopsy | Absent | Characteristic when present, not required for diagnosis |
| Response to 5-aminosalicylates | Effective for induction and maintenance | Not effective for maintenance; sulfasalazine has only modest benefit in mild colonic disease |
| Surgical cure | Colectomy is curative | Resection is not curative — recurrence at the anastomosis is expected |
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]
| Criterion | Scoring |
|---|---|
| General well-being (previous day) | 0 very well, 1 slightly below par, 2 poor, 3 very poor, 4 terrible |
| Abdominal pain (previous day) | 0 none, 1 mild, 2 moderate, 3 severe |
| Number of liquid/soft stools (previous day) | 1 point per stool, no upper cap |
| Abdominal mass | 0 none, 1 dubious, 2 definite, 3 definite and tender |
| Complications (1 point each) | Arthralgia, uveitis, erythema nodosum, aphthous ulcers, pyoderma gangrenosum, anal fissure, new fistula, abscess |
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]
| Domain | Scoring (0-3 each) |
|---|---|
| Stool frequency | 0 normal number of stools for that patient, 1 one to two more than normal, 2 three to four more than normal, 3 five or more more than normal |
| Rectal bleeding | 0 none, 1 streaks of blood, 2 obvious blood most of the time, 3 blood alone passed |
| Physician global assessment | 0 normal, 1 mild disease, 2 moderate disease, 3 severe disease |
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.
Treatment Targets
- 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.
Choose Initial Treatment
Ulcerative colitis, mild-moderate
1st line, any extent oral 5-aminosalicylate (mesalazine or sulfasalazine) for induction and maintenance.[2][7]
1st line, left-sided or distal disease add rectal 5-aminosalicylate to the oral regimen, or use rectal therapy alone for isolated proctitis — combined oral plus rectal 5-ASA outperforms either route alone for left-sided and distal disease.
2nd line — use when 5-ASA fails to induce remission or is not tolerated oral budesonide MMX or rectal budesonide for induction only.
Ulcerative colitis, moderate-severe or steroid-refractory
Escalate directly to advanced therapy — a biologic (anti-TNF, vedolizumab, or an anti-IL-23 agent), a JAK inhibitor, or an S1P receptor modulator — rather than cycling through repeated 5-ASA or corticosteroid courses; the trigger for escalation is moderate-severe disease activity at diagnosis, or failure to achieve steroid-free remission after a single 5-ASA-plus-corticosteroid induction attempt.
Acute severe ulcerative colitis (hospitalized)
1st line IV corticosteroids (hydrocortisone or methylprednisolone), with response assessed at 72 hours using objective criteria (stool frequency, CRP).[8]
Rescue therapy — trigger is inadequate response to IV corticosteroids by 72 hours infliximab or IV cyclosporine, with continuous surgical consultation throughout — colectomy is the appropriate next step if rescue therapy also fails, or immediately if any red-flag complication develops at any point.
Crohn disease, mild-moderate
1st line, ileocecal/right-colon disease oral budesonide for induction.
Alternative — more extensive or colonic disease, or when budesonide is inadequate a conventional oral corticosteroid (prednisone) for induction.
Do not use mesalazine for Crohn's disease 5-ASA is not effective for induction or maintenance of Crohn's disease; sulfasalazine has only modest benefit, limited to mild colonic disease.
Crohn disease, moderate-severe
1st line for patients with poor-prognosis features early combined therapy — a biologic (anti-TNF preferred by the strongest evidence base) started together with a thiopurine or methotrexate, rather than a conventional step-up sequence; the trigger for this “top-down” approach is the presence of poor-prognosis features (young age at diagnosis, perianal disease, deep ulceration, extensive small bowel involvement, or a steroid-requiring presentation at diagnosis).[9]
Conventional step-up — reasonable when poor-prognosis features are absent corticosteroid induction followed by a thiopurine or methotrexate for maintenance, escalating to a biologic only if steroid-dependence or treatment failure develops.
Crohn disease, fistulizing or perianal
1st line anti-TNF therapy (infliximab has the strongest evidence for fistula closure), combined with antibiotics (metronidazole and/or ciprofloxacin) and surgical drainage (seton placement) for any associated abscess.[9]
Maintenance therapy, both diseases
Never use a corticosteroid for maintenance therapy — oral and rectal corticosteroids, including budesonide, induce remission but have no proven maintenance benefit, and continued or repeated use only accumulates harm (adrenal suppression, osteoporosis, avascular necrosis, cataracts, increased infection risk); a patient requiring multiple corticosteroid courses within a short period needs their maintenance regimen reassessed and optimized, not another course of steroids.[1][2]
Non-Pharmacologic Treatment
- 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.
Special Populations
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.
Monitoring & Follow-Up
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.
Common Errors to Avoid
- 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.
Clinical Decision Algorithm
Drug Tables
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 | Dosage | Adverse effects | Comments |
|---|---|---|---|
| Mesalazine (oral) | Induction: 2.4-4.8 g/day PO in divided doses or once daily Maintenance: 2-4 g/day PO Children: Weight-based dosing per current product labelling -- confirm with pediatric GI before use | Abdominal pain, headache, nausea, rare hypersensitivity pneumonitis/hepatitis, rare interstitial nephritis | Not effective for induction or maintenance of Crohn's disease. All oral formulations are comparably effective in UC. |
| Mesalazine (rectal) | Induction, enema: 4 g PR at bedtime Induction, suppository: 1 g PR at bedtime Maintenance, enema: 2 g PR at bedtime, or 4 g every 2nd-3rd night Maintenance, suppository: 1 g PR every 2nd-3rd night, per response | Local irritation, rectal urgency, worsening hemorrhoids | Suppositories treat proctitis only; enemas reach the splenic flexure. Combined oral plus rectal outperforms either route alone for left-sided/distal disease. |
| Sulfasalazine | Induction (adults): 1 g PO 3-4 times daily, up to 4-6 g/day as tolerated Maintenance (adults): 500 mg PO 2-4 times daily | GI upset, headache, rare hemolytic anemia (higher risk with G6PD deficiency), reversible oligospermia, sulfa hypersensitivity | Give with folic acid. Cross-reactivity risk with sulfonamide antibiotic allergy. Modest benefit in mild colonic Crohn's disease; ineffective in small bowel CD. |
| Olsalazine | Induction: 500 mg PO 4 times daily Maintenance: 500 mg PO twice daily | Secretory diarrhea, minimized by gradual dose titration | Alternative 5-ASA formulation for patients intolerant of other agents. |
Drug Class: Corticosteroids, systemic (induction only -- never for maintenance)
| Drug | Dosage | Adverse effects | Comments |
|---|---|---|---|
| Prednisone | Induction (adults): 40-60 mg PO once daily for 2-4 weeks, then taper by 5 mg/week to 20 mg/day, then by 2.5 mg/week to discontinuation | Hyperglycemia, insomnia, mood change, hypertension, osteoporosis and avascular necrosis with repeated courses, adrenal suppression | Taper after clinical improvement; never continue as maintenance. Repeated courses within a short period signal a need to reassess the maintenance regimen. |
| Hydrocortisone (IV) | Acute severe colitis: 300-400 mg/day IV in divided doses | Hyperglycemia, infection risk, mood change, fluid retention | 1st-line induction for acute severe UC/CD; assess response at 72 hours; transition to oral prednisone taper once stable. |
| Methylprednisolone (IV) | Acute severe colitis: 40-60 mg/day IV until stable, then switch to oral prednisone taper | Hyperglycemia, infection risk, mood change, fluid retention | Alternative IV corticosteroid for acute severe colitis; equivalent role to IV hydrocortisone. |
Drug Class: Corticosteroids, locally-acting (induction only)
| Drug | Dosage | Adverse effects | Comments |
|---|---|---|---|
| Budesonide (oral) | CD induction: 9 mg PO once daily for up to 8 weeks, then taper to 6 mg once daily for about 2 weeks before stopping UC induction: 9 mg PO once daily for up to 8 weeks | Fewer systemic effects than conventional corticosteroids, but still risks adrenal suppression with prolonged use | Entocort targets ileal/right-colon CD; Cortiment MMX targets colonic UC. Not for maintenance beyond the induction course. |
| Budesonide (rectal foam) | Induction: 1 metered dose PR twice daily for 2 weeks, then once daily at bedtime for 4 more weeks | Local irritation, low but real systemic absorption with adrenal suppression risk | For mild-moderate distal UC (proctitis/proctosigmoiditis) up to about 40 cm from the anal verge. |
Drug Class: Immunomodulators
| Drug | Dosage | Adverse effects | Comments |
|---|---|---|---|
| Azathioprine | Maintenance (adults): 2-2.5 mg/kg PO once daily | Myelosuppression, hepatotoxicity, pancreatitis (usually within the first month), increased risk of lymphoproliferative disease and nonmelanoma skin cancer with prolonged use | Check TPMT/NUDT15 status before starting. Ineffective as induction monotherapy -- start together with a corticosteroid or biologic. |
| Mercaptopurine (6-MP) | Maintenance (adults): 1-1.5 mg/kg PO once daily | Myelosuppression, hepatotoxicity, pancreatitis, increased lymphoproliferative disease and skin cancer risk with prolonged use | Reasonable alternative if a patient develops nausea on azathioprine -- shares the same monitoring requirements. |
| Methotrexate | CD induction: 25 mg IM/SC once weekly CD maintenance: 15 mg IM/SC once weekly | Nausea, oral ulcers, hepatotoxicity, hypersensitivity pneumonitis, bone marrow suppression | CD only -- not effective in UC. Give with folic acid to reduce toxicity. Contraindicated in pregnancy. |
| Cyclosporine | Rescue therapy, IV: 2-4 mg/kg/day IV continuous infusion, target trough 250-450 ng/mL Step-down, oral: 8 mg/kg/day PO in divided doses, target trough 100-250 ng/mL | Nephrotoxicity, hypertension, seizure, gum hyperplasia, opportunistic infection, electrolyte imbalance | Steroid-refractory acute severe UC rescue only, as a bridge to thiopurine/biologic maintenance or colectomy -- inpatient specialist monitoring required. |
Drug Class: Anti-TNF-alpha biologics
| Drug | Dosage | Adverse effects | Comments |
|---|---|---|---|
| Infliximab | Induction: 5 mg/kg IV at weeks 0, 2, and 6 Maintenance: 5 mg/kg IV every 8 weeks (up to 10 mg/kg or every 4 weeks if response is lost) Fistulizing CD: Same induction/maintenance regimen -- strongest evidence base for fistula closure | Infusion reaction, infection, reactivation of latent TB/hepatitis B, rare lupus-like syndrome, worsening heart failure | Complete TB and hepatitis B/C screening before starting. Combining with a thiopurine improves durability in CD. |
| Adalimumab | Induction: 160 mg SC at week 0, 80 mg SC at week 2 Maintenance: 40 mg SC every 2 weeks (may increase to weekly if response is lost) | Injection-site reaction, infection, reactivation of latent TB/hepatitis B | Self-injectable -- an option for patients who prefer to avoid infusion visits. Complete the same pre-biologic screening as infliximab. |
| Golimumab | Induction: 200 mg SC at week 0, 100 mg SC at week 2 Maintenance: 50 mg SC every 4 weeks (may increase to 100 mg every 4 weeks if needed) | Infection, injection-site reaction, liver test abnormalities | UC only -- not approved in Canada for Crohn's disease. |
Drug Class: Anti-integrin and anti-IL-12/23 / anti-IL-23 biologics
| Drug | Dosage | Adverse effects | Comments |
|---|---|---|---|
| Vedolizumab | Induction: 300 mg IV at weeks 0, 2, and 6 Maintenance, IV: 300 mg IV every 8 weeks Maintenance, SC: 108 mg SC every 2 weeks, starting after at least 2 IV induction doses | Nasopharyngitis, arthralgia, headache, upper respiratory tract infection | Gut-selective mechanism gives a favourable infection profile. In a head-to-head trial, vedolizumab outperformed adalimumab for clinical remission and endoscopic improvement in moderate-severe UC.[14] |
| Ustekinumab | Induction: Single weight-based IV infusion (260 mg if 55 kg or less, 390 mg if over 55 to 85 kg, 520 mg if over 85 kg) Maintenance: 90 mg SC every 8 weeks, starting at week 8 (may increase to every 4 weeks) | Headache, nasopharyngitis, injection-site reaction, arthralgia | Anti-IL-12/23 agent (targets the shared p40 subunit). Maintenance frequency can be increased for an inadequate response. |
| Risankizumab | CD induction: 600 mg IV at weeks 0, 4, and 8 CD maintenance: 360 mg SC every 8 weeks, starting at week 12 UC induction: 1200 mg IV at weeks 0, 4, and 8 UC maintenance: 180 mg or 360 mg SC every 8 weeks, starting at week 12, using the lowest effective dose | Headache, infection, injection-site reaction | Anti-IL-23 agent. A further option after anti-TNF or anti-integrin failure in either disease. |
| Guselkumab | Induction: 200 mg IV at weeks 0, 4, and 8, or 400 mg SC (as two 200 mg injections) at weeks 0, 4, and 8 Maintenance: 100 mg SC at week 16 then every 8 weeks (200 mg SC every 4 weeks, starting week 12, for an inadequate response) | Headache, infection, injection-site reaction | Anti-IL-23 agent approved for both CD and UC. |
| Mirikizumab | UC induction: 300 mg IV at weeks 0, 4, and 8 UC maintenance: 200 mg SC every 4 weeks, starting at week 12 CD induction: 900 mg IV at weeks 0, 4, and 8 CD maintenance: 300 mg SC every 4 weeks, starting at week 12 | Headache, infection, injection-site reaction, arthralgia | Anti-IL-23 agent approved for both UC and CD. |
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 | Dosage | Adverse effects | Comments |
|---|---|---|---|
| Tofacitinib | Induction: 10 mg PO twice daily for at least 8 weeks Maintenance: 5 mg PO twice daily (10 mg twice daily may be continued in some patients, using the lowest effective dose) | Infection, herpes zoster, elevated LDL, rare VTE/MACE (class boxed warning) | UC only -- not approved in Canada for Crohn's disease. Confirm effective contraception before starting. |
| Upadacitinib | UC induction: 45 mg PO once daily for 8 weeks CD induction: 45 mg PO once daily for 12 weeks Maintenance, both diseases: 15 mg or 30 mg PO once daily, based on severity and response | Infection, elevated lipids, rare VTE/MACE (class boxed warning) | Approved for both UC and CD. Confirm effective contraception before starting. |
| Ozanimod | Dose escalation: 0.23 mg once daily days 1-4, then 0.46 mg once daily days 5-7 Maintenance: 0.92 mg PO once daily from day 8 | Transient bradycardia at initiation, infection, elevated liver enzymes | UC only. Requires baseline ECG/labs and the dose-escalation schedule to limit first-dose bradycardia. |
| Etrasimod | Maintenance: 2 mg PO once daily, no escalation required | Infection, elevated liver enzymes, bradycardia (less pronounced than ozanimod) | UC only. No dose-escalation schedule required, though first-dose cardiac monitoring applies to patients with certain baseline cardiac conditions. |
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.
| Drug | Dosage | Adverse effects | Comments |
|---|---|---|---|
| Metronidazole | Adults: 500 mg PO twice to 3 times daily for 2-4 weeks | Metallic taste, peripheral neuropathy with prolonged use, disulfiram-like reaction with alcohol | Short course for CD perianal/fistulizing disease or pouchitis, often combined with ciprofloxacin. |
| Ciprofloxacin | Adults: 500 mg PO twice daily for 2-4 weeks | GI upset, tendinopathy, QT prolongation | Short course for CD perianal/fistulizing disease or pouchitis, often combined with metronidazole. |
| Loperamide | Adults: 2 mg PO after each loose stool, maximum 16 mg/day | Constipation; avoid in active severe colitis given toxic megacolon risk | For symptomatic control of diarrhea in mild or quiescent disease only. |
| Diphenoxylate/atropine | Adults: 5 mg (2 tablets) PO 3-4 times daily, maximum 20 mg/day | Anticholinergic effects (dry mouth, blurred vision), CNS effects, sedation; avoid in active severe colitis given toxic megacolon risk | More CNS adverse effects than loperamide because of the atropine component. Taper to the lowest effective dose once diarrhea is controlled. |
| Codeine | Adults: 15-60 mg PO every 4-6 hours as needed | Constipation, sedation, dependence with prolonged use | A CYP2D6 polymorphism can substantially reduce conversion to active drug in some patients. Avoid morphine/meperidine, or restrict to short-term use only. |
| Folic acid | With methotrexate: 1 mg PO once daily | Well tolerated at this dose | Co-administer with methotrexate to reduce methotrexate-related adverse effects. |
| Cholestyramine | Adults: 4 g PO 1-3 times daily, mixed with liquid | GI upset, can bind and reduce absorption of other oral drugs | For bile-salt-induced diarrhea after terminal ileal resection. Separate other oral medications by at least 1 hour before or 4-6 hours after. |
References
- ACG Clinical Guideline: Management of Crohn's Disease in Adults — American Journal of Gastroenterology, American College of Gastroenterology (Lichtenstein GR, Loftus EV, Afzali A, Long MD, Barnes EL, Isaacs KL, Ha CY). Am J Gastroenterol 2025;120(6):1225-1264
- ACG Clinical Guideline Update: Ulcerative Colitis in Adults — American Journal of Gastroenterology, American College of Gastroenterology (Rubin DT, Ananthakrishnan AN, Siegel CA, Barnes EL, Long MD). Am J Gastroenterol 2025;120(6):1187-1224
- Consensus statements on the risk, prevention, and treatment of venous thromboembolism in inflammatory bowel disease: Canadian Association of Gastroenterology — Gastroenterology (Nguyen GC, Bernstein CN, Bitton A, et al.). Gastroenterology 2014;146(3):835-848
- A simple index of Crohn's-disease activity — The Lancet (Harvey RF, Bradshaw JM). Lancet 1980;1(8167):514
- Cortisone in ulcerative colitis: final report on a therapeutic trial — British Medical Journal (Truelove SC, Witts LJ). Br Med J 1955;2(4947):1041-1048
- STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target Strategies in IBD — Gastroenterology (Turner D, Ricciuto A, Lewis A, et al.). Gastroenterology 2021;160(5):1570-1583
- Clinical Practice Guidelines for the Medical Management of Nonhospitalized Ulcerative Colitis: The Toronto Consensus — Gastroenterology, Canadian Association of Gastroenterology (Bressler B, Marshall JK, Bernstein CN, et al.). Gastroenterology 2015;148(5):1035-1058
- Treatment of Hospitalized Adult Patients With Severe Ulcerative Colitis: Toronto Consensus Statements — American Journal of Gastroenterology, Canadian Association of Gastroenterology (Bitton A, Buie D, Enns R, et al.). Am J Gastroenterol 2012;107(2):179-194
- Canadian Association of Gastroenterology Clinical Practice Guideline for the Management of Luminal Crohn's Disease — Journal of the Canadian Association of Gastroenterology (Panaccione R, Steinhart AH, Bressler B, et al.). J Can Assoc Gastroenterol 2019;2(3):e1-e34
- The Toronto Consensus Statements for the Management of Inflammatory Bowel Disease in Pregnancy — Gastroenterology (Nguyen GC, Seow CH, Maxwell C, et al.). Gastroenterology 2016;150(3):734-757
- Cardiovascular and Cancer Risk with Tofacitinib in Rheumatoid Arthritis — New England Journal of Medicine (Ytterberg SR, Bhatt DL, Mikuls TR, et al.). N Engl J Med 2022;386(4):316-326
- Canadian labelling for all JAK inhibitors to include risks of serious heart-related problems, fatal blood clots and cancer — Health Canada, Recalls and Safety Alerts. Health Canada Safety Review, updated 2022
- ACG Clinical Guideline Update: Preventive Care in Inflammatory Bowel Disease — American Journal of Gastroenterology, American College of Gastroenterology (Farraye FA, Melmed GY, Lichtenstein GR, Barnes EL, Limketkai BN, Caldera F, Kane S). Am J Gastroenterol 2025;120(7):1447-1473
- Vedolizumab versus Adalimumab for Moderate-to-Severe Ulcerative Colitis — New England Journal of Medicine (Sands BE, Peyrin-Biroulet L, Loftus EV, et al.). N Engl J Med 2019;381(13):1215-1226
Professional reference only. Apply clinical judgment and verify patient-specific decisions against current authoritative guidance and product information.