Inflammatory Bowel Disease

Meet the patient

A 24-year-old postgraduate presents with four months of diarrhoea, cramping right-lower-quadrant pain worse after meals, a 6 kg weight loss, and — almost as an afterthought — a perianal skin tag his GP treated as haemorrhoids. His stools are sometimes blood-streaked. His CRP is raised, his faecal calprotectin is 480, and a stool culture is negative.^[1][2]

Two questions now sit live and they govern everything that follows: is this Crohn's or ulcerative colitis? (the ileocolonoscopy, the histology and the MRI enterography decide) and is he high-risk enough to start a biologic now rather than climb a ladder? (the phenotype — stricturing, penetrating, perianal, young — decides).^[4]

Two diseases, one umbrella — the face-off that earns the marks

IBD is not two diseases fought in parallel — it is one immune-driven process read through three instruments: the endoscope, the biopsy, and the cross-sectional scan. The split between Crohn's and UC is the single most reproduced fact in a gastroenterology viva, so learn it as a face-off with one discriminator line beneath.^[1][3]

^[1]

The discriminator line: rectal sparing plus perianal fistulae plus granulomas points to Crohn; continuous rectal-origin bloody diarrhoea with pseudopolyps points to UC. When the picture is mixed and the work-up incomplete, the honest label is IBD-unclassified (10 to 15 percent) — not a fudge, a working diagnosis that settles after imaging and histology mature.^[1]

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The three classification axes you reproduce at viva

Classify along three axes — disease type, anatomy (Montreal), and activity — and never blur them. Examiners ask for all three, in that order, because each changes the management sentence.^[1][2][3]

Axis 1 — disease type: Crohn versus UC versus IBD-unclassified (above).^[1]

Axis 2 — anatomy (the Montreal classification). This is the language of every IBD letter and trial, reproduced verbatim:^[1]

^[1]

Axis 3 — activity scores. These set the target in treat-to-target and the threshold for hospitalisation in acute severe disease:^[1]

• Truelove and Witts (acute severe UC): severe attacks are defined by the Truelove and Witts criteria — the Oxford series of 51 severe episodes was selected on exactly these criteria — and a severe attack means admission for intensive medical therapy with intravenous and rectal hydrocortisone.^[7]
• Day-3 (Travis, Oxford) criteria: more than 8 stools on day 3, or a stool frequency of 3 to 8 with CRP above 45 mg/L — 85 percent of such patients require colectomy on that admission.^[7]
• Mayo score (UC): the trial metric of UC activity (range 0 to 12, higher scores meaning more active disease); GEMINI I defined clinical remission as a Mayo score of 2 or less with no subscore above 1.^[19]
• CDAI (Crohn): remission is a score of 150 or less — the endpoint of the budesonide and methotrexate trials.^[9][16]

The smoking paradox — the single most examinable fact in IBD

Smoking protects ulcerative colitis and destroys Crohn disease. Memorise it once, in both directions, because it is the one risk factor an examiner will twist.^[1]

In Crohn's, smoking roughly doubles the risk of stricturing and penetrating complications, raises the surgical and re-operation rate, and accelerates post-operative recurrence — quitting is a genuine disease-modifying intervention. In UC, current smokers have about half the risk, and quitting raises it — so UC often declares itself in the year after a patient stops. The mechanism is imperfectly understood (mucosal mucus, immune modulation, microbiome) but the clinical fact is rock-solid.^[1]

The second paradox — appendectomy. Done for true appendicitis before age 20, it is protective against UC (about a 50 percent reduction). In Crohn's it is associated with more severe ileal disease. Both paradoxes are viva gold.^[1]

How common, and who gets it

IBD is no longer a Western disease. Prevalence is now above 0.3 percent in North America, Northern Europe and Australasia — and the "second wave" is sweeping newly industrialised regions (South Asia, East Asia, the Middle East, South America) as diets urbanise. The global burden is above 7 million people, onset is bimodal (peak 15 to 30 years; a smaller second peak over 60), and the aetiology is the classic gene-environment-microbe-immune quartet.^[1]

Risk factors to run on autopilot: family history (first-degree relatives carry a 10- to 15-fold risk; monozygotic twin concordance is about 50 percent for CD, 15 percent for UC), the smoking split above, a Western low-fibre high-processed diet, early-life antibiotics, Caesarean birth, and urban living. The named susceptibility loci — NOD2/CARD15 (ileal, stricturing Crohn's), ATG16L1 and IRGM (autophagy, ileal Crohn's), IL23R (both diseases), HLA-DRB1 star 0103 (severe UC) — account for roughly a quarter of heritability.^[2]

Why it happens — four factors, one inflamed gut

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IBD is the prototype polygenic disease where genes, microbiome, barrier and immunity conspire. Each factor earns its place because it names a drug target or a bedside act.^[1][2]

1. Genes — over 240 risk loci; the functional clusters (bacterial sensing via NOD2, autophagy via ATG16L1/IRGM, the IL-23/Th17 axis) explain both the inflammation and the biologic targets.^[2]
2. Microbiome (dysbiosis) — reduced diversity, loss of the butyrate-producer Faecalibacterium prausnitzii, expansion of adherent-invasive E. coli in Crohn's and Ruminococcus gnavus in UC. Dysbiosis is both cause and consequence of inflammation.^[2]
3. Barrier dysfunction — the mucus layer (MUC2), tight junctions (claudins, occludin, ZO-1) and epithelial renewal are impaired, letting luminal antigen translocate to the lamina propria.^[1]
4. Immune dysregulation — in Crohn's, lamina propria CD4 T cells polarise to Th1/Th17 under IL-12 and IL-23 (the targets of ustekinumab and risankizumab); in UC the signature is atypical Th2 with NK-cell IL-13. TNF-alpha is the final common effector in both — the rationale for anti-TNF therapy.^[5]

Etymology for viva gold: the disease was named for Burrill Bernard Crohn, the New York physician whose 1932 paper with Ginzburg and Oppenheimer described "regional ileitis". Crohn was first author only because the paper was presented alphabetically — his colleagues contributed as much. The eponym survived because the disease kept looking the same wherever it was found.^[2]

Clinical presentation — the two fingerprints

Crohn's creeps; ulcerative colitis bleeds. Hold that contrast and the rest slots in.^[1]

Crohn disease — variable, segmental, often insidious. Crampy right-lower-quadrant pain after meals, chronic diarrhoea (non-bloody in pure small-bowel disease; bloody only when the colon is involved), weight loss and fatigue from malabsorption and cytokine-driven cachexia, low-grade fever, a palpable right-lower-quadrant mass of thickened ileum, aphthous mouth ulcers, and — in a third — perianal disease (skin tags, fissures, fistula-in-ano, abscess) that may precede the bowel symptoms by years.^[2]

Ulcerative colitis — bloody diarrhoea, urgency, tenesmus. The cardinal triad, with left-lower-quadrant cramping and rectal pain in proctitis. Systemic features — fever, tachycardia, weight loss — escalate with severity. The emergency end of the spectrum is acute severe UC and toxic megacolon (below).^[1][3]

The extraintestinal manifestations — sort them as parallel or independent

Every IBD patient gets a full-body look, because the disease spills outside the gut in ways that track — or do not track — the bowel activity. Sort them into two buckets and the management follows.^[1]

^[1]

The discriminator: uveitis, pyoderma gangrenosum, axial arthritis and PSC run their own course — controlling the gut does not control them. Treating the bowel alone and assuming the skin or the eye will follow is the recurring trainee error.^[1]

The diagnosis — three instruments, one answer

Diagnosis is a correlation, never a single test. You assemble the clinical picture, the ileocolonoscopy with biopsies, the cross-sectional imaging (MRE for Crohn's small bowel), the biomarkers, and — critically — the exclusion of infection.^[1][2][3]

Ileocolonoscopy with segmental biopsies is the cornerstone. Take multiple biopsies from the terminal ileum and every colonic segment (5 or more to maximise granuloma yield in Crohn's); record the macroscopic pattern (continuous vs skip, cobblestone vs friability, pseudopolyps) and send for histology and CMV PCR in severe disease. A normal colonoscopy does not exclude Crohn's — the disease may live in the small bowel, which is why magnetic resonance enterography is mandatory when the suspicion is high.^[1]

Cross-sectional imaging. MRE is preferred for small-bowel Crohn's (mural inflammation, strictures, fistula, abscess, the "comb sign" of mesenteric hypervascularity) and is radiation-free — vital in young patients. Pelvic MRI is the gold standard for mapping perianal fistula anatomy. CT is reserved for the acute abdomen (abscess, perforation, obstruction).^[1]

Biomarkers. CRP tracks Crohn's better than ESR. Faecal calprotectin above 150 to 250 micrograms per gram strongly suggests active intestinal inflammation in the right setting, and a normal calprotectin has a high negative predictive value for IBD in primary care — the single best non-invasive triage test. Serology (p-ANCA positive in 60 to 70 percent of UC, ASCA in 50 to 70 percent of Crohn's) helps separate indeterminate colitis but is not diagnostic.^[1]

^{[7] [10] [13] [15] [12] [14]}

The differential — exclude infection before you immunosuppress

The single non-negotiable rule: prove the diarrhoea is not infection before you reach for steroids or a biologic. Infection mimics IBD, triggers IBD flares, and turns immunosuppression into a catastrophe if missed.^[1][2][3]

^[1]

The classic trap — ileocaecal tuberculosis versus ileocaecal Crohn's. This is the highest-stakes differential in endemic regions. TB gives caseating granulomas, transverse (not longitudinal) ulcers, a patulous ileocaecal valve, and ascites or nodes; Crohn's gives non-caseating granulomas, aphthous and longitudinal ulcers, and skip lesions. Send IGRA, a chest radiograph, and an ascitic ADA where relevant — because starting anti-TNF in undiagnosed TB is a preventable death.^[1]

Acute severe ulcerative colitis — the gastrointestinal emergency

Acute severe UC (ASUC) is an emergency. The mortality is 1 to 3 percent even in expert centres, and every hour of delay costs colon and sometimes life. Humour is off here; this is a resuscitation problem with a strict protocol.^[1][3]

The threshold is the Truelove and Witts criteria — a severe attack of colitis with systemic upset. The moment a severe attack is confirmed, the patient is admitted and intensive medical therapy begins: intravenous and rectal hydrocortisone, with daily stool counts and CRP — the two variables that discriminated outcome in the Oxford cohort.^[7]

^{[7] [8] [12]}

The mantra for ASUC: IV steroids on day 1, Travis on day 3, rescue on day 3 to 5, surgery by day 7 if rescue fails — and the surgeon is in the conversation from the start.^[1]

Toxic megacolon — a dreaded complication of inflammatory or infectious colitis, most commonly associated with ulcerative colitis or ileocolonic Crohn's disease, and diagnosed by clinical systemic toxicity plus imaging showing colonic dilatation — is a surgical emergency on top of the medical one: nil by mouth, IV fluids and electrolytes, IV steroids, broad-spectrum antibiotics, and urgent surgical review for colectomy. Perforation, uncontrolled haemorrhage, and refractory obstruction are immediate indications for laparotomy.^[25]

Treat-to-target — STRIDE-II, the framework examiners now quote

The days of "control the symptoms and see" are over. STRIDE-II sets objective targets — clinical remission plus biochemical remission (CRP and faecal calprotectin) plus endoscopic remission — reassessed at named time-points, with therapy escalated whenever the target is missed.^[4][6]

• Week 0 — baseline clinical activity, CRP, faecal calprotectin, endoscopy (Mayo for UC, SES-CD for Crohn's); set the target.^[4]
• Week 10 to 14 — reassess clinical and biochemical response (CRP, calprotectin).^[4]
• Months 6 to 12 — endoscopic reassessment, the new standard. Target: Mayo endoscopic subscore 0 to 1 (ideally 0) in UC; SES-CD under 3 in Crohn's.^[4]
• Long-term — dysplasia surveillance in UC; MRE every 6 to 12 months in Crohn's small-bowel disease; ileocolonoscopy at 6 to 12 months after Crohn's resection (Rutgeerts), escalating prophylaxis if i2 to i4.^[4]

The classic trap: treating to a falling symptom score while the mucosa stays inflamed. Symptoms lie; the endoscope tells the truth. A patient who feels well but has persistent ulceration is heading for stricture, surgery and cancer — escalate on the endoscopy, not the symptom diary.^[4]

The drug ladder — name the drug, name the dose

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The ladder is real, but it bends. In low-risk disease you climb it (5-ASA, then steroids, then immunomodulator, then biologic). In high-risk Crohn's — young, stricturing, penetrating, perianal, extensive small-bowel — you go top-down: an early biologic with an immunomodulator prevents the irreversible structural damage that step-up allows. The prognostic argument now overrides the historical sequence.^[4][6]

5-aminosalicylates (mesalazine). First-line for mild-to-moderate active UC: mesalazine 2.4 g or 4.8 g once daily (MMX formulation) — clinical and endoscopic remission at 8 weeks in 40.5 and 41.2 percent versus 22.1 percent on placebo.^[10] Combination oral plus rectal 5-ASA beats oral alone for induction of remission (relative risk of no remission 0.65, NNT 5 — Ford meta-analysis).^[11] The awkward truth examiners test: mesalamine underperforms in Crohn's — controlled-ileal-release budesonide 9 mg once daily beat slow-release mesalamine 2 g twice daily for remission of active ileal or ileocaecal Crohn's (69 vs 45 percent at 8 weeks), which makes budesonide the first-line choice there.^[9]

Corticosteroids — induce remission, never maintain it. The Crohn's methotrexate trial enrolled patients chronically active despite at least three months of prednisone — the definition of steroid-dependent disease — and it was weekly methotrexate, not more steroid, that achieved steroid-free remission.^[16] Budesonide 9 mg once daily (controlled ileal release) induces remission in active ileal or ileocaecal Crohn's with less adrenal suppression — morning plasma cortisol was normal in 67 percent of budesonide-treated patients.^[9] In the severe UC attack, every episode in the Oxford series received intravenous and rectal hydrocortisone.^[7]

Thiopurines (azathioprine). The benchmark immunomodulator dose is azathioprine 2.5 mg/kg daily (SONIC): corticosteroid-free clinical remission at week 26 in 30.0 percent of patients with moderate-to-severe Crohn's on azathioprine monotherapy — significantly less than infliximab monotherapy (44.4 percent) and combination therapy (56.8 percent), with mucosal healing following the same order (16.5, 30.1 and 43.9 percent).^[18] Combination anti-TNF plus azathioprine is the evidence-based backbone for steroid-sparing maintenance in moderate-to-severe disease.

Methotrexate. Intramuscular methotrexate 25 mg once weekly for 16 weeks induced clinical remission in 39.4 percent of patients with chronically active Crohn's despite long-term steroids, versus 19.1 percent on placebo, with lower total prednisone use; remission was a CDAI of 150 or less off steroids.^[16] Maintenance: 15 mg intramuscularly once weekly kept 65 percent in remission at week 40 versus 39 percent on placebo.^[17]

Anti-TNF biologics. The class that transformed the field after Targan's 1997 infliximab trial proved anti-TNF worked in refractory Crohn's.^[5]

• Infliximab 5 mg/kg IV at weeks 0, 2 and 6, then every 8 weeks for moderate-to-severe Crohn's, and rescue in severe UC refractory to high-dose intravenous steroids (5 mg/kg on days 0, 14 and 42). Combination with azathioprine 2.5 mg/kg daily beat either alone for corticosteroid-free remission at week 26 — 56.8, 44.4 and 30.0 percent respectively (SONIC) — and ciclosporin was not superior to infliximab as ASUC rescue (treatment failure 60 vs 54 percent).^[18][8]
• Adalimumab 160 mg subcutaneously at week 0 then 80 mg at week 2 is the optimal induction regimen (remission 36 vs 12 percent on placebo — CLASSIC-I), then 40 mg every other week maintains response and remission (CHARM).^[22][23]

The newer biologics and small molecules. Vedolizumab 300 mg IV at weeks 0 and 2, then every 8 weeks (or every 4 weeks) for maintenance — gut-selective blockade of lymphocyte trafficking: response at week 6 in 47.1 vs 25.5 percent on placebo, remission at week 52 in 41.8 vs 15.9 percent (GEMINI I).^[19] Ustekinumab — a monoclonal antibody to the p40 subunit of interleukin-12 and interleukin-23: intravenous induction (130 mg or about 6 mg/kg), then subcutaneous 90 mg every 8 or 12 weeks (UNITI).^[21] Tofacitinib 10 mg twice daily for 8 weeks, then 5 mg or 10 mg twice daily for maintenance — an oral JAK inhibitor for moderate-severe UC: induction remission 18.5 and 16.6 percent vs 8.2 and 3.6 percent on placebo (OCTAVE 1 and 2), maintenance remission 34.3 and 40.6 vs 11.1 percent (OCTAVE Sustain), with higher rates of overall and serious infection during induction.^[20]

Before any biologic or immunosuppressant: exclude latent TB (IGRA and chest radiograph), hepatitis B and HIV; verify and update vaccinations (varicella, hepatitis B, MMR, HPV, influenza, pneumococcal); counsel on the methotrexate and JAK-inhibitor contraception rules.^[1]

Surgery — when the drugs stop working

Surgery in UC is curative of the colonic disease; surgery in Crohn's is palliative of the segment. That one-sentence contrast is viva gold and it reframes the whole conversation with the patient.^[1]

UC — restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA). Usually staged (subtotal colectomy with end ileostomy, then pouch construction, then ileostomy closure). It cures the colitis and removes most of the cancer risk, at the price of chronic pouchitis in 30 to 50 percent and pouch failure in 5 to 10 percent, and a real fertility cost in young women (consider a staged procedure). An end ileostomy alone is the safer choice for frail or steroid-dependent patients.^[1]

Crohn's — segmental resection of the diseased bowel (ileocolonic, segmental colonic, or strictureplasty to spare bowel length); perianal disease needs seton drainage, fistulotomy, LIFT or advancement flap. The line every candidate must reproduce: recurrence at the anastomosis is the rule (Rutgeerts i0 to i4) — 70 to 90 percent endoscopic recurrence within a year — which is why post-operative prophylaxis (thiopurine, anti-TNF, or anti-IL23 in high-risk patients) is now standard, not optional.^[2]

Complications — and the preventable-harm list

The complications separate into the acute structural, the chronic systemic, and the long-term malignant — and most are preventable.^[1][3]

^{[1] [13] [12]}

Colorectal cancer is the long shadow of colonic IBD. Risk rises with duration, extent, concomitant PSC, prior dysplasia, and a family history of colorectal cancer. Surveillance colonoscopy with chromoendoscopy begins at 8 to 10 years of extensive colitis (sooner and yearly if PSC), because early dysplasia is flat and easy to miss with white light alone.^[1]

How IBD patients come to harm — the preventable list:^[1]

• Death from unrecognised ileocaecal TB treated as Crohn's with anti-TNF — the preventable death.
• Delayed colectomy in fulminant ASUC because "the steroids might still work" on day 7.^[1]
• A pelvic abscess given anti-TNF without drainage — sepsis on immunosuppression.^[1]
• A patient with 10 years of extensive UC who never had a surveillance colonoscopy, presenting with cancer.
• A young woman left on long steroids for "steroid-dependent disease" because no one added a thiopurine — osteoporosis, diabetes, adrenal suppression.
• A flare loaded with immunosuppression without a stool test for C. difficile or CMV.
• VTE in a bed-bound flare because LMWH was forgotten.

Special populations

Pregnancy. Outcome is best when the disease is in remission at conception — active disease raises preterm birth and low birth weight. Continue maintenance therapy through pregnancy (5-ASA, azathioprine and infliximab are acceptable; give the last infliximab at 16 to 20 weeks to minimise neonatal exposure). Methotrexate is teratogenic — stop before conception in women and men. Vaginal delivery is acceptable except with active perianal disease or an IPAA (pouch-vaginal fistula risk). Plan mode of delivery in a joint obstetric-gastroenterology clinic.^[1]

The elderly. More left-sided or distal disease, more comorbidity, higher infection risk on immunosuppression — vedolizumab is favoured for its gut-selective safety profile. Watch polypharmacy, falls, and colorectal cancer screening.^[1]

Post-operative Crohn's. Recurrence is the rule. High-risk patients (smoking, penetrating disease, prior resection, two or more predictors) get biologic prophylaxis within 4 weeks of surgery; lower-risk patients get ileocolonoscopy at 6 to 12 months, with prophylaxis started if Rutgeerts i2 or higher.^[2]

Children. Phenotype is more severe — extensive UC, ileocolonic Crohn's with upper GI involvement, rapid progression. Growth failure and delayed puberty may be the first presentation. Exclusive enteral nutrition for 6 to 8 weeks is as effective as steroids for inducing remission in mild-moderate paediatric Crohn's — and it preserves growth. Consider monogenic IBD in infantile-onset disease.^[1]

The evidence — guidelines and the one trial to name

The framework is built on the ACG UC guideline (Rubin 2019), the ECCO Crohn's and UC therapeutics guidelines (Torres 2020; Raine 2022), and the STRIDE and STRIDE-II treat-to-target initiatives (Peyrin-Biroulet 2015; Turner 2021).^{[1][2][3][4][6]}

The single trial examiners expect you to cite is Targan et al., NEJM 1997 — the original infliximab induction trial in moderate-severe Crohn's, the study that proved anti-TNF worked and opened the entire biologic era.^[5]

^[1]

The mantra: Crohn is transmural, skip and not cured by the knife; UC is mucosal, continuous and cured by it — and the smoking goes the opposite way in each.^[1][2]

Ward-round test — three stems

Stem 1 — the young man from the top of the topic (answer)ShowHide

A 24-year-old with four months of diarrhoea, right-lower-quadrant pain, weight loss, a perianal skin tag, raised CRP and calprotectin 480, negative stool culture. What is the next step, and how do you decide between a ladder and a biologic? Model: This is suspected Crohn's until proven otherwise — a relapsing systemic inflammatory disease of the gastrointestinal tract with extraintestinal and perianal features.^[24] The work-up combines ileocolonoscopy with cross-sectional imaging — MRI or CT — and biomarkers, plus exclusion of infection before any immunosuppression.^[24] The strategy question is answered by trial evidence: in moderate-to-severe disease, infliximab 5 mg/kg at weeks 0, 2 and 6 then every 8 weeks, combined with azathioprine 2.5 mg/kg daily, gave the highest corticosteroid-free remission (56.8 percent) and mucosal healing (43.9 percent) rates in SONIC — the top-down combination.^[18] If it is mild inflammatory ileocaecal disease, budesonide 9 mg once daily (69 percent remission at 8 weeks) is the first-line induction choice, having beaten mesalamine head-to-head.^[9] Treat to a target: clinical remission, endoscopic healing, and normalisation of CRP and calprotectin (STRIDE-II).^[4]

Stem 2 — the UC flare that turns severe (answer)ShowHide

A 32-year-old with known extensive UC presents with 9 bloody stools in 24 hours, pulse 108, temperature 38.1, Hb 98 g/L. What do you do in the first 12 hours? Model: She has an acute severe attack of ulcerative colitis — the Truelove and Witts definition of severe colitis. Admit for intensive medical therapy: intravenous and rectal hydrocortisone, with daily stool counts and CRP — the two variables that predict outcome.^[7] On day 3 apply the Oxford criteria: more than 8 stools, or 3 to 8 stools with CRP above 45 mg/L — 85 percent of such patients require colectomy on that admission.^[7] If high-dose intravenous steroids fail, rescue with infliximab 5 mg/kg on days 0, 14 and 42, or ciclosporin 2 mg/kg per day IV for one week then oral to day 98 — the randomised trial found them equivalent (treatment failure 54 vs 60 percent), with azathioprine started at day 7 in responders.^[8] Remember the approximately two-fold VTE risk of IBD (summary RR 2.20).^[12]

Stem 3 — the smoking paradox as a viva trap (answer)ShowHide

An examiner asks: "A 30-year-old smoker is diagnosed with Crohn's ileitis. What single non-pharmacological intervention has the biggest effect on his disease course, and why is the answer the opposite in ulcerative colitis?" Model: Smoking cessation. In Crohn's, smoking roughly doubles the risk of stricturing and penetrating complications, raises the surgical and re-operation rate, and accelerates post-operative recurrence — quitting is a genuine disease-modifying intervention. In ulcerative colitis the relationship inverts: current smokers have about half the risk, and quitting raises it, so UC often declares itself in the year after a patient stops. Treat smoking cessation as a therapy in Crohn's, not a lifestyle footnote.^[1]

References25ShowHide

1. [1]Rubin DT, Ananthakrishnan AN, Siegel CA, et al. ACG Clinical Guideline: Ulcerative Colitis in Adults Am J Gastroenterol, 2019.PMID 30840605
2. [2]Torres J, Bonovas S, Doherty G, et al. ECCO Guidelines on Therapeutics in Crohn's Disease: Medical Treatment J Crohns Colitis, 2020.PMID 31711158
3. [3]Raine T, Bonovas S, Burisch J, et al. ECCO Guidelines on Therapeutics in Ulcerative Colitis: Medical Treatment J Crohns Colitis, 2022.PMID 34635919
4. [4]Turner D, Ricciuto A, Lewis A, et al. 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, 2021.PMID 33359090
5. [5]Targan SR, Hanauer SB, van Deventer SJ, et al. A short-term study of chimeric monoclonal antibody cA2 to tumor necrosis factor alpha for Crohn's disease. Crohn's Disease cA2 Study Group N Engl J Med, 1997.PMID 9321530
6. [6]Peyrin-Biroulet L, Sandborn W, Sands BE, et al. Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE): Determining Therapeutic Goals for Treat-to-Target Am J Gastroenterol, 2015.PMID 26303131
7. [7]Travis SP, Farrant JM, Ricketts C, et al. Predicting outcome in severe ulcerative colitis Gut, 1996.PMID 8984031
8. [8]Laharie D, Bourreille A, Branche J, et al. Ciclosporin versus infliximab in patients with severe ulcerative colitis refractory to intravenous steroids: a parallel, open-label randomised controlled trial Lancet, 2012.PMID 23063316
9. [9]Thomsen OO, Cortot A, Jewell D, et al. A comparison of budesonide and mesalamine for active Crohn's disease N Engl J Med, 1998.PMID 9691103
10. [10]Kamm MA, Sandborn WJ, Gassull M, et al. Once-daily, high-concentration MMX mesalamine in active ulcerative colitis Gastroenterology, 2007.PMID 17241860
11. [11]Ford AC, Khan KJ, Achkar JP, et al. Efficacy of oral vs. topical, or combined oral and topical 5-aminosalicylates, in Ulcerative Colitis: systematic review and meta-analysis Am J Gastroenterol, 2012.PMID 22108446
12. [12]Yuhara H, Steinmaus C, Corley DA, et al. Meta-analysis: the risk of venous thromboembolism in patients with inflammatory bowel disease Aliment Pharmacol Ther, 2013.PMID 23550660
13. [13]Eaden JA, Abrams KR, Mayberry JF The risk of colorectal cancer in ulcerative colitis: a meta-analysis Gut, 2001.PMID 11247898
14. [14]Tysk C, Lindberg E, Järnerot G, et al. Ulcerative colitis and Crohn's disease in an unselected population of monozygotic and dizygotic twins. A study of heritability and the influence of smoking Gut, 1988.PMID 3396969
15. [15]Orholm M, Munkholm P, Langholz E, et al. Familial occurrence of inflammatory bowel disease N Engl J Med, 1991.PMID 1984188
16. [16]Feagan BG, Rochon J, Fedorak RN, et al. Methotrexate for the treatment of Crohn's disease N Engl J Med, 1995.PMID 7816064
17. [17]Feagan BG, Fedorak RN, Irvine EJ, et al. A comparison of methotrexate with placebo for the maintenance of remission in Crohn's disease N Engl J Med, 2000.PMID 10833208
18. [18]Colombel JF, Sandborn WJ, Reinisch W, et al. Infliximab, azathioprine, or combination therapy for Crohn's disease N Engl J Med, 2010.PMID 20393175
19. [19]Feagan BG, Rutgeerts P, Sands BE, et al. Vedolizumab as induction and maintenance therapy for ulcerative colitis N Engl J Med, 2013.PMID 23964932
20. [20]Sandborn WJ, Su C, Sands BE, et al. Tofacitinib as Induction and Maintenance Therapy for Ulcerative Colitis N Engl J Med, 2017.PMID 28467869
21. [21]Feagan BG, Sandborn WJ, Gasink C, et al. Ustekinumab as Induction and Maintenance Therapy for Crohn's Disease N Engl J Med, 2016.PMID 27959607
22. [22]Hanauer SB, Sandborn WJ, Rutgeerts P, et al. Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn's disease: the CLASSIC-I trial Gastroenterology, 2006.PMID 16472588
23. [23]Colombel JF, Sandborn WJ, Rutgeerts P, et al. Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: the CHARM trial Gastroenterology, 2007.PMID 17241859
24. [24]Baumgart DC, Sandborn WJ Crohn's disease Lancet, 2012.PMID 22914295
25. [25]Autenrieth DM, Baumgart DC Toxic megacolon Inflamm Bowel Dis, 2012.PMID 22009735