Management of Inflamattory bowel disease
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Management of Inflamattory bowel disease
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Clinical Management Summary: Inflammatory Bowel Disease (IBD)
1. Overview
Inflammatory bowel disease (IBD) encompasses two main conditions - Ulcerative Colitis (UC) and Crohn's Disease (CD) - both characterized by chronic, relapsing-remitting intestinal inflammation of unclear etiology involving dysregulated immune responses in genetically susceptible individuals.
| Feature | Ulcerative Colitis | Crohn's Disease |
|---|---|---|
| Location | Colon and rectum (contiguous) | Any part of GI tract (skip lesions) |
| Depth | Mucosal/submucosal | Transmural |
| Rectal involvement | Almost always | Variable |
| Fistulas/abscesses | Rare | Common |
| Smoking effect | Protective | Worsens disease |
| Surgery curative? | Yes (colectomy) | No |
2. Classification of Disease Severity
Ulcerative Colitis (Mayo Score / Truelove-Witts)
- Mild: <4 stools/day, no systemic upset, normal CRP
- Moderate: 4-6 stools/day, minimal systemic upset
- Severe (Fulminant): >6 bloody stools/day, systemic features (fever, tachycardia, anemia, raised CRP/ESR)
Crohn's Disease (Harvey-Bradshaw / CDAI)
- Mild-Moderate: Ambulatory, tolerating oral intake, no dehydration
- Moderate-Severe: >10% weight loss, fever, anemia, abdominal mass
- Severe/Fulminant: Persistent symptoms despite outpatient therapy, cachexia, obstruction, abscess
3. Medical Management
Step 1: Aminosalicylates (5-ASA) - First Line for Mild-Moderate UC
Agents:
- Sulfasalazine 2-4 g/day (split doses) - first generation; sulfapyridine carrier
- Mesalamine (oral, topical) - preferred for tolerability
- Olsalazine, balsalazide - alternatives
Indications:
- Mild-moderate active UC: induction and maintenance of remission
- Topical (suppository/enema) for proctitis or proctosigmoiditis
- Efficacy in CD is unproven, though some clinicians use mesalamine for colonic CD
Notes:
- Sulfasalazine: up to 40% intolerance; supplement with folic acid 1 mg/day (impairs folate absorption)
- Mesalamine: rare interstitial nephritis with high doses; monitor renal function
- 5-ASA drugs are not useful for maintaining surgically induced remission in CD
- (Goldman-Cecil Medicine; Katzung Pharmacology 16e)
Step 2: Corticosteroids - Active Flares
| Agent | Route | Indication | Dose |
|---|---|---|---|
| Prednisone/Prednisolone | Oral | Moderate flares | 40-60 mg/day, taper over 8-12 wks |
| Methylprednisolone | IV | Severe/hospitalized | 40-60 mg/day IV |
| Hydrocortisone | IV | Fulminant colitis/toxic megacolon | 100 mg every 6 hrs |
| Budesonide (Entocort) | Oral CR | Mild-moderate ileal/right colon CD | 9 mg/day |
| Budesonide MMX (Uceris) | Oral | Mild-moderate UC colonic | pH >7 release |
| Hydrocortisone enema/foam | Rectal | Proctitis/sigmoid disease | Topical |
Key Principles:
- Corticosteroids are not maintenance therapy - do not use long-term
- Budesonide is slightly less effective than prednisolone but has significantly fewer systemic effects (first-pass hepatic metabolism ~90%)
- Taper systematically once remission achieved
- (Katzung Pharmacology 16e; Goldman-Cecil Medicine)
Step 3: Immunomodulators - Steroid-Sparing / Maintenance
Thiopurines (Azathioprine / 6-Mercaptopurine)
- Doses: AZA 2-2.5 mg/kg/day; 6-MP 1-1.5 mg/kg/day
- Onset: Median 17 weeks (due to 6-thioguanine nucleotide kinetics - do not expect rapid response)
- Check TPMT activity before initiation (deficiency = risk of severe myelosuppression)
- Monitor: CBC, LFTs every 3 months
- Uses: Maintenance in UC and CD; combination with anti-TNF to reduce immunogenicity
Adverse effects: Myelosuppression, hepatotoxicity, pancreatitis, increased lymphoma risk (especially with combination therapy), non-melanoma skin cancer
Methotrexate
- 15-25 mg IM/SC weekly for induction; 15 mg/week for maintenance in CD
- Evidence strongest in CD (not established in UC)
- Folate supplementation required; contraindicated in pregnancy
- Monitor: CBC, LFTs; hepatic fibrosis with prolonged use
Step 4: Biologic Therapies - Moderate to Severe Disease
Anti-TNF Agents
| Agent | Route | Approved For | Induction | Maintenance |
|---|---|---|---|---|
| Infliximab | IV | CD + UC | 5 mg/kg at 0, 2, 6 wks | 5 mg/kg every 8 wks |
| Adalimumab | SC | CD + UC | 160 mg → 80 mg at 2 wks | 40 mg every 2 wks |
| Golimumab | SC | UC | 200 mg → 100 mg at 2 wks | 100 mg every 4 wks |
| Certolizumab pegol | SC | CD | 400 mg at 0, 2, 4 wks | 400 mg every 4 wks |
Efficacy: Symptomatic improvement ~60%, remission ~30% in moderate-severe CD at induction. ~50% maintain response at maintenance. About one-third lose response over time (due to antibody formation or pharmacokinetic failure).
Important considerations before initiation:
- Screen for latent TB (tuberculin skin test or IGRA) - mandatory
- Screen for hepatitis B (reactivation risk)
- Avoid in active serious infection, heart failure (NYHA Class III-IV), demyelinating disease
- Infliximab IV is more effective than SC adalimumab for UC - mechanism uncertain but likely pharmacokinetic
Anti-Integrin (Vedolizumab)
- Selective gut-lymphocyte trafficking inhibitor (α4β7 integrin)
- Approved for moderate-severe UC and CD
- Gut-selective - safer immunological profile, preferred in patients with risk factors for systemic immunosuppression
- IV: 300 mg at 0, 2, 6 weeks, then every 8 weeks maintenance
- BSG 2025 guideline recommends vedolizumab for UC induction/maintenance
Anti-IL-12/23 (Ustekinumab)
- Approved for moderate-severe UC and CD
- IV induction (weight-based ~6 mg/kg), SC maintenance 90 mg every 8-12 wks
- Favorable safety profile; alternative for patients failing anti-TNF
Selective Anti-IL-23 (Risankizumab, Mirikizumab)
- Newer agents targeting p19 subunit of IL-23
- Risankizumab: Approved for moderate-severe CD and UC
- Mirikizumab: Approved for moderate-severe UC
- BSG 2025 guideline: risankizumab suggested for UC; both suggested based on recent network meta-analysis evidence
- (BSG IBD Guidelines 2025, Gut 2025; 74:s1-s101)
JAK Inhibitors (Small Molecule Oral Agents)
| Agent | Target | Indication | Dose |
|---|---|---|---|
| Tofacitinib | Pan-JAK | Moderate-severe UC | 10 mg BID induction ≥8 wks; 5-10 mg BID maintenance |
| Upadacitinib | Selective JAK1 | Moderate-severe UC (+ CD) | 45 mg OD induction 8 wks; 15-30 mg OD maintenance |
| Filgotinib | Selective JAK1 | Moderate-severe UC | 200 mg OD |
Advantages: Oral, rapid onset, no immunogenicity
Safety concerns:
- Herpes zoster activation (consider varicella zoster vaccination prior)
- Dyslipidemia - monitor lipid profile
- Thromboembolism risk (especially tofacitinib) - screen cardiovascular risk
- Lymphoma risk (particularly with tofacitinib in patients >50 years or cardiovascular risk)
- Upadacitinib: large effect size in BSG 2025 NMA for UC; recommended for induction and maintenance
- (Goldman-Cecil Medicine; BSG 2025; AGA Evidence Synthesis 2024 - PMID 39425738)
4. Treatment Strategy by Disease Type
Ulcerative Colitis - Step-Up Approach
Mild-Moderate:
5-ASA (oral ± topical) → If insufficient → Budesonide MMX
→ Oral corticosteroids
Moderate-Severe (steroid-dependent/refractory):
Anti-TNF (infliximab preferred) OR vedolizumab OR ustekinumab
OR JAK inhibitor (tofacitinib/upadacitinib)
± AZA/6-MP combination with anti-TNF
Acute Severe UC (hospitalized):
IV hydrocortisone 100 mg q6h or methylprednisolone 40-60 mg/day
→ No response at 3 days → IV cyclosporine 2-4 mg/kg/day OR infliximab
→ Failure → Colectomy
Crohn's Disease - Stratified Approach
Mild-Moderate Ileocecal/Ileal:
Budesonide 9 mg/day
(5-ASA: no proven benefit in CD)
Moderate-Severe:
Anti-TNF (infliximab/adalimumab) - early biologic preferred
+ AZA/6-MP or MTX combination
OR vedolizumab, ustekinumab, risankizumab
OR upadacitinib (JAK1i)
Perianal CD:
Antibiotics (ciprofloxacin/metronidazole) + seton placement
Anti-TNF (infliximab) - gold standard
Combined surgical + biologic approach
MRI pelvis mandatory for assessment
Luminal/structuring CD:
Endoscopic balloon dilation (short strictures <4-5 cm, accessible)
Strictureplasty or resection (surgical)
Early Biologic Therapy in CD: A 2024 meta-analysis confirmed that early biologic treatment decreases risk of surgery in CD (but not in UC) - (PMID 37506265)
5. Acute Severe/Fulminant Colitis and Toxic Megacolon
Initial Management (Hospitalize All Patients)
- IV fluids, electrolyte replacement, DVT prophylaxis
- IV corticosteroids: hydrocortisone 100 mg IV q6h or methylprednisolone 40-60 mg/day
- NPO or restricted diet; NG suction if ileus
- Abdominal X-ray daily to monitor colonic dilation (toxic megacolon: transverse colon >6 cm)
- Surgical consultation on admission; stoma site marking by enterostomal therapist
- Blood transfusion if Hb <80 g/L
No Response at 3 Days - Rescue Therapy
- Cyclosporine 2-4 mg/kg/day IV (80% initial response in severe fulminant colitis; bridges to AZA)
- Infliximab 5 mg/kg IV (alternative rescue)
- Monitor closely - delay in surgery increases mortality from 2% to 50%
Absolute Surgical Indications
- Free colonic perforation
- Progressive colonic dilation unresponsive to medical therapy
- Uncontrolled hemorrhage
- Progressive sepsis with hemodynamic instability
- Failure to improve within 48 hours (relative indication)
- (Current Surgical Therapy 14e; Sleisenger & Fordtran)
Surgery of choice: Subtotal colectomy with end ileostomy (definitive restorative proctocolectomy with IPAA later)
6. Surgical Management
Ulcerative Colitis
| Procedure | Indication | Notes |
|---|---|---|
| Subtotal colectomy + ileostomy | Acute severe/emergency | Safest in unstable patient |
| Total proctocolectomy + IPAA (J-pouch) | Elective, sphincter preservation | Gold standard for UC |
| Total proctocolectomy + Brooke ileostomy | Unable/unsuitable for IPAA | Permanent ileostomy |
Surgery is curative in UC - indicated also for dysplasia, cancer risk, refractory disease
Crohn's Disease
- Surgery is not curative - disease recurs at anastomosis in up to 70-80%
- Goal: bowel preservation (strictureplasty preferred over resection when possible)
- Indications: obstruction, fistula, abscess, cancer, medical refractory disease
Post-surgical CD:
- Anti-TNF (infliximab/adalimumab) or vedolizumab after ileocolonic resection reduces recurrence in high-risk patients (BSG 2025)
- 5-ASA and purine analogues are not recommended for post-surgical maintenance in CD (BSG 2025)
- Colonoscopy at 6-12 months post-surgery to assess recurrence (Rutgeerts score)
7. Special Situations
IBD in Pregnancy
- Mesalamine: safe throughout pregnancy; continue maintenance
- Corticosteroids: safe for flare control
- AZA/6-MP: continue if needed (risks of uncontrolled disease > teratogenicity risk)
- Anti-TNF: generally safe through second trimester; certolizumab preferred (no Fc, minimal placental transfer)
- Methotrexate: contraindicated in pregnancy
- Stop anti-TNF late third trimester (especially infliximab) to reduce neonatal immunosuppression; delay live vaccines in infant until 6 months
IBD and Infection Risk
- Screen all patients before biologic/immunosuppressant therapy:
- TB (IGRA or TST)
- Hepatitis B surface antigen + core antibody
- HIV, VZV serology
- Vaccinate: influenza, pneumococcus, hepatitis B, VZV (live vaccines before immunosuppression only)
- 2025 ECCO Guidelines update: JAK inhibitors and selective IL-23 agents have distinct infection profiles - risk stratification now drug- and host-specific, not class-wide
- (ECCO Opportunistic Infections Guidelines 2025)
IBD and Cancer Surveillance
- UC with pancolitis or left-sided colitis >8-10 years: colonoscopy every 1-2 years
- Primary sclerosing cholangitis (PSC) + IBD: annual surveillance from diagnosis
- Chromoendoscopy preferred technique for dysplasia detection
- Avoid long-term combination immunosuppression (anti-TNF + thiopurine) in young males (hepatosplenic T-cell lymphoma risk)
8. Extraintestinal Manifestations (EIMs)
| System | Manifestation | Relationship to Bowel Activity |
|---|---|---|
| Skin | Erythema nodosum | Parallels bowel disease |
| Skin | Pyoderma gangrenosum (1-2% of IBD) | May persist despite remission |
| Eyes | Episcleritis, uveitis (5-8% each) | Variable |
| Joints | Peripheral arthropathy, ankylosing spondylitis | Peripheral parallels bowel; axial independent |
| Liver | Primary sclerosing cholangitis (PSC) | Independent of bowel activity |
| Hepatobiliary | Cholelithiasis, fatty liver | Common in CD |
Management: Treat underlying IBD first. Anti-TNF agents effective for most EIMs. PSC: no proven medical therapy - ursodeoxycholic acid not recommended; liver transplant for end-stage.
9. Monitoring and Follow-Up
| Parameter | Frequency |
|---|---|
| Clinical assessment (HBI/CDAI or partial Mayo) | Every visit |
| CRP, fecal calprotectin | Every 3-6 months |
| CBC, LFTs, renal function | Every 3-6 months (more frequent on immunosuppressants) |
| Thiopurine metabolite levels (6-TGN) | If subtherapeutic response or toxicity |
| Drug levels (infliximab trough) | If loss of response; target >3 mcg/mL trough |
| Colonoscopy | Per surveillance protocol |
| DEXA scan | Patients on prolonged steroids |
| Skin check | Annual; esp. patients on thiopurines/anti-TNF |
Treat-to-target strategy:
- Target: clinical remission and mucosal healing (endoscopic remission)
- Biomarker target: CRP normal, fecal calprotectin <150-250 mg/kg
- Adjust therapy based on objective markers, not symptoms alone
10. Recent Evidence Updates (2024-2026)
| Study | Finding | PMID |
|---|---|---|
| AGA Evidence Synthesis 2024 (UC) | Network meta-analysis comparing advanced therapies for moderate-severe UC; upadacitinib ranked highest for induction/maintenance | 39425738 |
| AGA Evidence Synthesis 2025 (CD) | Comparative efficacy of advanced therapies for moderate-severe CD | 41114682 |
| Meta-analysis 2024 | Early biologic therapy reduces surgery risk in CD but not UC | 37506265 |
| BSG IBD Guidelines 2025 | Comprehensive update covering all drug classes, surgical decisions, special populations; strong recommendation for upadacitinib in UC | BSG Gut 2025;74:s1 |
| ECCO Infections 2025 | Updated drug-specific infection risk stratification for all IBD biologics and small molecules | ECCO 2025 |
| FMT meta-analysis 2025 | Fecal microbiota transplantation shows benefit in UC induction/remission in select patients | 40246750 |
References
- Sleisenger and Fordtran's Gastrointestinal and Liver Disease (Sleisenger)
- Goldman-Cecil Medicine, International Edition, 2-Volume Set
- Katzung's Basic and Clinical Pharmacology, 16th Edition
- Goodman & Gilman's Pharmacological Basis of Therapeutics
- Current Surgical Therapy, 14th Edition
- Sabiston Textbook of Surgery, Biological Basis of Modern Surgical Practice
- BSG IBD Guidelines 2025 - Moran G, Gordon M et al. Gut 2025; 74:s1-s101
- AGA Evidence Synthesis 2024 (UC) - Ananthakrishnan AN et al. Gastroenterology 2024 Dec [PMID: 39425738]
- AGA Evidence Synthesis 2025 (CD) - Singh S et al. Gastroenterology 2025 [PMID: 41114682]
- Early biologics meta-analysis 2024 - Law CCY et al. Inflamm Bowel Dis 2024 [PMID: 37506265]
- ECCO Opportunistic Infections 2025 - Gisbert J, Yanai H et al.
Clinical Note: The IBD treatment landscape changed significantly in 2024-2025. Upadacitinib (selective JAK1 inhibitor) now has the strongest evidence base for UC induction and maintenance per AGA and BSG 2025 analyses. Selective IL-23 agents (risankizumab, mirikizumab) are now first-line advanced therapy options alongside anti-TNF. The traditional step-up approach is being replaced by early top-down biologic therapy in moderate-severe CD, given the 2024 meta-analysis confirming surgery risk reduction with early biologics.
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Management of Inflammatory Bowel Disease
30-Mark Exam Essay Answer
Introduction
Inflammatory bowel disease (IBD) is a chronic, relapsing-remitting condition encompassing two principal entities: Ulcerative Colitis (UC) and Crohn's Disease (CD). UC is characterised by continuous mucosal inflammation limited to the colon and rectum, while CD is a transmural, granulomatous inflammation that can affect any part of the gastrointestinal tract from mouth to anus, classically involving the terminal ileum and proximal colon with skip lesions. The management of IBD is complex and requires a multidisciplinary approach integrating medical therapy, nutritional support, endoscopic surveillance, and surgical intervention where appropriate. The overarching goal is to induce and maintain remission, achieve mucosal healing, prevent complications, and preserve quality of life.
Assessment and Disease Classification
Before initiating treatment, disease severity must be stratified. In UC, the Truelove-Witts criteria and Mayo Score are used: mild disease involves fewer than four stools per day with no systemic features; moderate disease involves four to six bloody stools with minimal systemic disturbance; and severe/fulminant disease involves more than six bloody stools daily with systemic features such as fever (>37.8°C), tachycardia (>90 bpm), anaemia (Hb <10.5 g/dL), and elevated ESR (>30 mm/hr). In CD, the Harvey-Bradshaw Index (HBI) or Crohn's Disease Activity Index (CDAI) guides severity assessment. Disease extent (proctitis, left-sided, extensive colitis in UC; ileal, colonic, ileocolonic, or perianal in CD) further guides the route and choice of therapy.
Medical Management
5-Aminosalicylates (5-ASA)
5-ASA drugs are the cornerstone of treatment for mild to moderate UC. Sulfasalazine (2-4 g/day), the original compound, combines 5-ASA with sulfapyridine; however, up to 40% of patients are intolerant due to sulfapyridine-related side effects including nausea, headache, oligospermia, and haematological toxicity. Folic acid 1 mg/day must be supplemented as sulfasalazine impairs folate absorption. Newer formulations - mesalamine, olsalazine, balsalazide - deliver 5-ASA to the colon via pH-dependent or bacterial cleavage mechanisms, with better tolerability. Topical preparations (suppositories, enemas) are particularly effective for proctitis and proctosigmoiditis. 5-ASA drugs are used for both induction and long-term maintenance of remission in UC. Importantly, their efficacy in CD is unproven and they are not recommended for post-surgical maintenance of remission in CD.
Corticosteroids
Corticosteroids are the primary agents for treating acute flares of both UC and CD. For moderate disease, oral prednisone or prednisolone 40-60 mg/day is initiated and tapered over 8-12 weeks once remission is achieved. For severe hospitalised disease, intravenous methylprednisolone 40-60 mg/day or hydrocortisone 100 mg every 6 hours is used. A critical principle is that corticosteroids are effective for induction but are not maintenance agents - they do not prevent relapse, and long-term use results in well-known complications including osteoporosis, adrenal suppression, hyperglycaemia, cataracts, and Cushing's syndrome.
Budesonide is a synthetic glucocorticoid with ~90% first-pass hepatic metabolism, offering high topical activity with minimal systemic bioavailability (~10%). Oral controlled-release budesonide 9 mg/day (Entocort - ileal/right colon release) is used for mild-moderate ileocecal Crohn's disease, while budesonide MMX (Uceris - colonic release) is used for mild-moderate UC. Although slightly less effective than prednisolone, budesonide carries significantly fewer systemic adverse effects.
Immunomodulators
In patients who are steroid-dependent, steroid-refractory, or have moderate-severe disease requiring maintenance therapy, immunomodulators are used. Azathioprine (AZA) 2-2.5 mg/kg/day or 6-mercaptopurine (6-MP) 1-1.5 mg/kg/day are the most widely used. These purine antimetabolites inhibit lymphocyte proliferation; however, their onset of action is delayed by a median of 17 weeks due to the slow accumulation of active 6-thioguanine nucleotides in cells - a fact patients must be counselled on. TPMT (thiopurine S-methyltransferase) activity must be checked before starting; TPMT deficiency results in excessive 6-thioguanine accumulation and severe, potentially fatal myelosuppression. Regular monitoring of FBC and LFTs is mandatory every 3 months. AZA and 6-MP are combined with anti-TNF biologics to reduce immunogenicity and improve clinical outcomes, though this combination carries a heightened risk of hepatosplenic T-cell lymphoma in young males under 35 years.
Methotrexate (15-25 mg IM/SC weekly for induction, 15 mg/week for maintenance) has established evidence in CD but not UC. Folate supplementation is required. It is absolutely contraindicated in pregnancy.
Biologic Therapy
For patients with moderate to severe IBD refractory to conventional therapies, biologic agents have transformed outcomes.
Anti-TNF Agents
Anti-tumour necrosis factor (anti-TNF) agents bind soluble and membrane-bound TNF-α, thereby suppressing the inflammatory cascade. Infliximab (chimeric IgG1), adalimumab (fully human IgG1), golimumab (fully human, UC only), and certolizumab pegol (PEGylated Fab fragment, CD only) are the available agents. Infliximab is given as an intravenous infusion at 5 mg/kg at weeks 0, 2, and 6 (induction), followed by 5 mg/kg every 8 weeks (maintenance); adalimumab is given subcutaneously at 160 mg then 80 mg at week 2, then 40 mg every 2 weeks. With induction therapy, approximately 60% of patients achieve symptomatic improvement and 30% achieve remission; with continued maintenance, 40-50% maintain remission. Approximately one-third of patients lose response over time, often due to anti-drug antibody formation or pharmacokinetic failure - therapeutic drug monitoring (target infliximab trough >3 mcg/mL) guides management.
Pre-treatment screening is mandatory before initiating any biologic: latent tuberculosis (IGRA or tuberculin skin test), hepatitis B serology, HIV status, and varicella zoster immune status. Prophylactic antituberculous therapy is given to IGRA-positive patients before commencing anti-TNF therapy. Anti-TNFs are contraindicated in active serious infection, NYHA Class III-IV cardiac failure, and demyelinating disease.
Certolizumab pegol, lacking an Fc region, has minimal placental transfer and is the preferred anti-TNF in pregnancy.
Vedolizumab (Anti-Integrin)
Vedolizumab is a gut-selective monoclonal antibody targeting the α4β7 integrin on gut-homing lymphocytes, preventing their extravasation into the intestinal mucosa. Its gut-selectivity confers a more favourable safety profile compared to anti-TNFs, with no increased systemic infection risk. It is approved for moderate-severe UC and CD and is particularly preferred in elderly patients, those with prior malignancy, or those at high risk for systemic immunosuppression. Dosing: 300 mg IV at weeks 0, 2, and 6, then every 8 weeks maintenance.
Anti-IL-12/23 (Ustekinumab)
Ustekinumab targets the p40 subunit shared by IL-12 and IL-23, blocking the TH1 and TH17 pathways implicated in IBD. It is approved for moderate-severe UC and CD. Induction is given as a single weight-based IV dose (~6 mg/kg), with SC maintenance of 90 mg every 8-12 weeks. It has an excellent safety profile and is an effective option after anti-TNF failure.
Selective Anti-IL-23 Agents (Risankizumab, Mirikizumab)
Newer agents targeting the p19 subunit of IL-23 selectively include risankizumab (approved for CD and UC) and mirikizumab (approved for UC). The 2025 BSG IBD Guidelines, based on an extensive network meta-analysis, position these agents alongside anti-TNF and vedolizumab as first-line advanced therapies for moderate-severe disease.
JAK Inhibitors (Small Molecules)
JAK inhibitors are orally administered small molecules offering rapid onset of action and no immunogenicity. Tofacitinib (pan-JAK inhibitor) is used in UC at 10 mg twice daily for induction (at least 8 weeks), then 5-10 mg twice daily for maintenance. Upadacitinib (selective JAK1 inhibitor) is given as 45 mg once daily for induction (8 weeks), then 15 or 30 mg once daily for maintenance; the 2024 AGA Evidence Synthesis and BSG 2025 Guidelines rank upadacitinib as having the largest effect size for UC induction and maintenance among advanced therapies. Filgotinib (selective JAK1) is an additional option. Safety concerns with JAK inhibitors include herpes zoster reactivation (VZV vaccination recommended prior), dyslipidaemia, thromboembolism (especially tofacitinib), and potential lymphoma risk in patients over 50 years or with cardiovascular risk factors.
Management of Acute Severe Colitis and Toxic Megacolon
Acute severe UC is a medical emergency requiring immediate hospitalisation. Management follows the Oxford Protocol:
- IV hydrocortisone 100 mg every 6 hours (or methylprednisolone 40-60 mg/day IV)
- IV fluid resuscitation, electrolyte correction
- DVT prophylaxis (LMWH)
- Daily abdominal X-ray to monitor colonic dilatation (toxic megacolon: transverse colon ≥6 cm)
- Surgical review on admission; stoma site marking by enterostomal therapist
- Avoid antidiarrhoeals and opioids (risk of precipitating toxic megacolon)
- Treat any concurrent C. difficile infection (vancomycin 125-500 mg QDS oral)
If there is no response to IV steroids at 72 hours, rescue therapy is indicated:
- Intravenous cyclosporine 2-4 mg/kg/day (achieves initial response in ~80%; bridges to AZA/6-MP)
- Infliximab 5 mg/kg IV as a single infusion (alternative to cyclosporine)
Crucially, delay in surgical intervention significantly worsens prognosis: mortality rises from 2% to 50% if perforation occurs. Surgical intervention is absolutely indicated in cases of free colonic perforation, progressive colonic dilatation unresponsive to medical therapy, uncontrolled haemorrhage, haemodynamic instability, or failure to improve within 48 hours of maximal medical therapy.
Surgical Management
Ulcerative Colitis
Surgery is potentially curative in UC. The standard emergency operation is a subtotal colectomy with end ileostomy, which is safe in the acutely ill, haemodynamically unstable patient; the rectum is preserved for later restorative surgery. The definitive elective operation is total proctocolectomy with ileal pouch-anal anastomosis (IPAA / J-pouch), which preserves continence and is the procedure of choice for elective colectomy in suitable patients. Total proctocolectomy with permanent Brooke ileostomy is reserved for those unsuitable for IPAA (sphincter dysfunction, mesorectal involvement, patient preference).
Surgical indications in UC include: acute severe colitis refractory to medical therapy, toxic megacolon, perforation, uncontrolled haemorrhage, and elective indications including steroid dependence, failure of biologic therapy, low-grade or high-grade dysplasia, and colorectal carcinoma.
Crohn's Disease
Surgery in CD is not curative - postoperative recurrence at the neo-terminal ileum occurs endoscopically in up to 70-80% of patients within one year without prophylaxis. The principle is intestinal conservation - strictureplasty is preferred over resection to preserve bowel length and prevent short bowel syndrome. Resection with primary anastomosis is appropriate for localised disease. Defunctioning ileostomy may be required for complex perianal or rectal disease.
Surgical indications in CD include: intestinal obstruction from stricture (not amenable to endoscopic dilation), enterocutaneous or internal fistulae causing morbidity, intra-abdominal abscess (after percutaneous drainage failure), failure of medical therapy, and malignancy.
Post-surgical CD prophylaxis: Anti-TNF therapy (infliximab/adalimumab) or vedolizumab is recommended after ileocolonic resection in patients at high risk of recurrence (smoking, perforating disease, prior resection). Colonoscopy at 6-12 months (Rutgeerts score) guides intensification of therapy. 5-ASA and purine analogues are not recommended for post-surgical maintenance in CD (BSG 2025).
Management of Complications
Perianal Crohn's Disease
Perianal involvement occurs in ~20% of CD patients. Management is multidisciplinary. MRI pelvis is the gold standard for fistula characterisation. Acute abscesses require surgical drainage; seton placement in the fistula tract reduces sepsis and allows anti-TNF therapy. Infliximab is the most effective medical therapy for perianal fistulising CD. Combined surgical (seton) and infliximab therapy achieves fistula closure in approximately 50% of patients. Antibiotics (metronidazole, ciprofloxacin) provide adjunctive benefit.
Intra-abdominal Abscesses
Percutaneous CT-guided drainage combined with systemic antibiotics is first-line, with outcomes equivalent to surgery in most cases. Anti-TNF therapy after drainage reduces recurrence. Surgical resection is reserved for cases where drainage is technically impossible, associated with a fibrostenotic stricture, or associated with clinical deterioration.
Extraintestinal Manifestations
Extraintestinal manifestations (EIMs) affect up to 40% of IBD patients. Erythema nodosum (2-4%) parallels bowel disease activity. Pyoderma gangrenosum (1-2%) may persist despite bowel remission and requires systemic therapy (steroids, CSA, anti-TNF). Episcleritis and uveitis (5-8% each) require ophthalmological assessment. Peripheral arthropathy parallels bowel disease; axial arthropathy/ankylosing spondylitis runs independently. Primary sclerosing cholangitis (PSC) - strongly associated with UC - runs independently of colonic disease, confers elevated cholangiocarcinoma risk, and may ultimately require liver transplantation.
Surveillance and Cancer Risk
Patients with IBD have an elevated risk of colorectal carcinoma related to duration and extent of colonic disease, concurrent PSC, and degree of mucosal inflammation. Surveillance colonoscopy with chromoendoscopy (targeted biopsies of dysplastic lesions) is recommended:
- From 8-10 years after disease onset in pancolitis or left-sided colitis
- Annually from diagnosis in PSC-IBD
- Frequency every 1-3 years based on risk stratification (low, intermediate, high risk)
Monitoring on Therapy
Patients on immunosuppressive and biologic therapy require systematic monitoring including: FBC, LFTs, and renal function every 3 months; therapeutic drug monitoring (infliximab trough levels) on loss of response; annual skin cancer check (particularly with thiopurines); lipid profile for JAK inhibitor users; and DEXA scan for those on prolonged corticosteroids.
Conclusion
The management of IBD has evolved substantially, shifting from a traditional step-up approach to a treat-to-target strategy aiming for both clinical remission and mucosal healing. The therapeutic armamentarium now spans 5-ASA, corticosteroids, immunomodulators, anti-TNF biologics, anti-integrins, anti-IL-23 agents, and oral JAK inhibitors. Surgical management remains essential for disease complications and refractory cases, with curative potential in UC and a bowel-preserving philosophy in CD. Optimal outcomes require a multidisciplinary team including gastroenterologists, colorectal surgeons, stoma therapists, dietitians, and IBD nurse specialists, guided by the most current evidence from the BSG 2025 and AGA 2024/2025 guidelines.
Examiner tip: A 30-mark answer on IBD management should cover: (1) classification/severity assessment, (2) medical therapy by step with specific drugs/doses, (3) biologics with mechanisms, (4) acute severe colitis protocol, (5) surgical indications and options for both UC and CD, (6) complications (perianal, abscess, EIMs), (7) surveillance, and (8) monitoring. This structure ensures all marking domains are addressed.
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