What it is:Inflammatory bowel disease is really two different diseases wearing one name. Ulcerative colitis (UC)is mucosal inflammation confined to the colon and rectum, always continuous, always starting at the rectum and working proximally. Crohn's disease (CD)is transmural inflammation that can hit anywhere from mouth to anus, classically the terminal ileum, and it skips around leaving normal bowel between diseased segments.
The core problem:In a genetically susceptible person, the gut microbiome triggers an immune response that never turns off. TNF-α is the shared final pathway driving inflammation in both diseases, which is why anti-TNF therapy works across both. The details of which cytokines dominate (Th1/Th17 in CD, Th2 in UC) explain why some newer biologics work better in one disease than the other.
What you do about it:Match the drug to three variables: which disease, how severe, and how much bowel is involved. Then think in two phases: induction(get them into remission) and maintenance(keep them there). Most drugs that induce remission also maintain it. Corticosteroids are the huge exception: great for induction, useless and harmful for maintenance.
Think of therapy as a ladder keyed to location + severity, not a single algorithm. Distal/proctitis UC gets treated topically (rectal therapy) even when extensive UC at the same severity gets systemic therapy. Mild-to-moderate disease starts with 5-ASA or budesonide; moderate-to-severe skips straight to systemic steroids for induction plus a biologic or immunomodulator for durable control. If you remember nothing else: steroids induce, they never maintain.
This comparison is tested constantly because the two diseases really do behave, look, and get treated differently once you get past "chronic GI inflammation."
| Feature | Ulcerative Colitis | Crohn's Disease |
|---|---|---|
| Location | Rectum first, extends proximally through the colon only | Anywhere mouth to anus; terminal ileum and cecum classic |
| Distribution | Continuous | Discontinuous / skip lesions |
| Depth | Mucosa and submucosa only | Transmural (full thickness) |
| Classic lesion | Crypt abscess (very common) | Granuloma, linear clefts, cobblestone appearance (all common) |
| Malaise / fever | Uncommon | Common |
| Abdominal pain / mass | Unusual / absent | Common |
| Fistulas, strictures | Rare | Common |
| Rectal bleeding | Common (bloody diarrhea is classic) | Common but can be non-bloody |
| Major complications | Toxic megacolon, colonic perforation, colorectal cancer | Strictures with obstruction, fistulas, abscesses, nutritional deficiency |
| Smoking | Protective (unusual!) | Worsens frequency and severity |
| NSAIDs | May trigger flares | May trigger flares |
| Serology | p-ANCA positive | Anti-Saccharomyces cerevisiaeantibodies (ASCA) positive |
Everyone assumes "bloody diarrhea = UC only." Wrong: CD can absolutely present with hematochezia too, it's just more classic and more consistentin UC. What actually separates them cleanly is distribution(continuous vs skip lesions) and depth(mucosal vs transmural), not bleeding pattern alone.
UC severity is graded by stool frequency plus systemic signs, and this grading is what determines whether you reach for topical 5-ASA or an ICU bed.
| Severity | Stools/day | Other findings |
|---|---|---|
| Mild(~2/3 of patients) | <4, ± blood | No systemic disturbance, ESR <30 mm/h |
| Moderate | >4 | Minimal systemic disturbance |
| Severe | >6, with blood | Fever, tachycardia, anemia, or ESR >30 mm/h |
| Fulminant | >10, continuous bleeding | Toxicity, abdominal tenderness, transfusion requirement, colonic dilation |
CD disease activity is tracked with composite indices like the Crohn's Disease Activity Index (CDAI), built from 7-day stool count, abdominal pain ratings, general well-being, antidiarrheal use, body weight, hematocrit, and presence of an abdominal mass, plus the shorter Harvey-Bradshaw Index. UC has its own composite scores (Mayo score, Ulcerative Colitis Activity Index) combining stool frequency, rectal bleeding, endoscopic appearance, and physician global assessment. You won't need to memorize the point cutoffs, just recognize these are the tools used to track response and define remission objectively instead of by gut feeling.
Every drug class in this chapter targets a specific step in the same broken pathway: susceptible genetics, a triggering microbial/environmental exposure, and an immune response that can't stand down.
No single cause has been pinned down, but four ingredients keep showing up together: genetics(first-degree relatives have up to a 20-foldincreased risk, extending even to second- and third-degree relatives), infectious/microbial triggers(mycobacteria, certain E. coli, Listeria, and other organisms implicated), environmental factors, and an abnormal innate immune response. The prevailing model is that gut microflora acts as the environmental trigger that lights up inflammation in someone who was already genetically loaded for it.
| Disease | Dominant cytokine pattern | Key players |
|---|---|---|
| Crohn's disease | Th1 / Th17 | ↑ IFN-γ, IL-12, IL-17A, IL-22 |
| Ulcerative colitis | Th2 | Different cytokine skew, p-ANCA positivity common |
| Both | Shared final pathway | TNF-α elevated in mucosa and intestinal lumen of both diseases |
Read the drug classes straight off the immunology. Anti-TNF agents(infliximab, adalimumab, certolizumab, golimumab) neutralize the cytokine shared by both diseases, which is why they work in UC and CD. Anti-IL-12/23 and anti-IL-23 agents(ustekinumab, risankizumab, mirikizumab, guselkumab) target the Th1/Th17 axis that's especially active in CD. Anti-integrin agents(vedolizumab, natalizumab) don't touch cytokines at all, they physically block leukocytes from adhering to gut endothelium and migrating in, which is why they're "gut-selective" with a different safety profile. 5-ASA compoundsact topically within the bowel lumen with an unclear but locally anti-inflammatory mechanism (inhibiting leukocyte motility, interfering with cytokine production) and are barely absorbed systemically, so they work best where they can physically contact inflamed mucosa.
Antineutrophil cytoplasmic antibodies (p-ANCA) show up in a high percentage of UC patients and less often in CD; patients with CD typically carry antibodies to Saccharomyces cerevisiae(ASCA), reflecting an abnormal immune reaction to intestinal organisms. Smoking is protective in UC but worsens CD, one of the genuinely strange asymmetries in this disease pair, and nobody fully understands why. NSAIDs can trigger disease occurrence or flares in both.
Because UC is mucosal and confined to the colon, its local complications are things like hemorrhoids, anal fissures, perirectal abscesses, and (in a minority) toxic megacolon, occurring in up to 7.9%of hospitalized UC patients. Because CD is transmural and can occur anywhere, its complications are structural: small bowel strictureswith obstruction, and fistula formation, which happens far more often than in UC since a full-thickness inflamed tract can burrow through to adjacent structures. This is the anatomic reason CD needs surgeons involved earlier and more often for drainage/resection of fistulizing disease, while UC surgery is more often a colectomy for disease control.
Both diseases run a relapsing-remitting course: bouts of active illness separated by intervals of quiet, sometimes for years.
| Ulcerative Colitis | Crohn's Disease | |
|---|---|---|
| Symptoms | Abdominal cramping, frequent BMs often with blood, weight loss, fever/tachycardia if severe | Malaise, fever, abdominal pain, frequent BMs, hematochezia, fistula, weight loss/malnutrition |
| Exam | Hemorrhoids, anal fissures, perirectal abscesses may be present | Abdominal mass and tenderness, perianal fissure or fistula |
| Labs | ↓ Hgb/Hct, ↑ ESR/CRP/fecal calprotectin, leukocytosis + hypoalbuminemia if severe, (+) p-ANCA | ↑ WBC/ESR/CRP/fecal calprotectin, (+) ASCA |
High fever, tachycardia, distended abdomen, elevated WBC, and a dilated colon on imaging. This is a UC emergency (up to 7.9% of hospitalized UC patients) that needs aggressive supportive care, IV steroids, and early surgical consultation, not another round of outpatient mesalamine.
Diagnosis is clinical plus objective confirmation: history, exam, labs, imaging, and endoscopy with biopsy. No single test rules IBD in or out.
CT, ultrasound, MRI, and endoscopy (colonoscopy, sigmoidoscopy, capsule endoscopy) localize and characterize disease, and biopsy confirms histology (crypt abscesses favor UC; granulomas favor CD).
It's cheap, noninvasive, and correlates with mucosal inflammation, which makes it a great tool for triage ("does this patient need a scope") and for monitoring a known IBD patient's trend without repeat colonoscopy. A normal fecal calprotectin makes active IBD unlikely; a rising one in a quiet patient is an early flag before symptoms fully declare themselves.
Your course material flags fecal calprotectinand fecal lactoferrinspecifically as the two biomarkers that reflect intestinal (not just systemic) inflammation, as opposed to ESR/CRP which rise with inflammation anywhere in the body. Know that distinction, it's an easy short-answer trap.
Goals:resolve the acute inflammatory process, resolve complications like fistulas or abscesses, control extraintestinal manifestations like arthritis, achieve and maintain remission, and reserve surgery for palliation or cure when medical therapy fails. Modern practice targets objective endpoints, mucosal healing and endoscopic remission, not just "the patient feels better" (the treat-to-targetapproach).
Ask two questions for every drug: (1) can it induce remission, (2) can it maintain it?Corticosteroids (oral or IV) are excellent inducers and terrible maintainers, they have no role in long-term control and should always be tapered off over 2-4 weeks once remission is reached. Biologics, thiopurines, methotrexate, and 5-ASA (in UC) generally do both. Cyclosporine and IV corticosteroids are induction/rescue-only tools.
Two variables drive the choice: extent(proctitis/distal vs extensive) and severity(mild, moderate, severe, fulminant).
| Severity / extent | Induction | Maintenance |
|---|---|---|
| Proctitis (mild-mod) | Rectal 5-ASA ± rectal corticosteroid | Rectal 5-ASA |
| Left-sided (mild-mod) | Rectal + oral 5-ASA ± oral budesonide MMX | Oral 5-ASA |
| Extensive (mild-mod) | Oral 5-ASA 2-3 g/day ± oral budesonide MMX 9 mg/day | Oral 5-ASA ≥2 g/day |
| Moderate-to-severe | Oral systemic corticosteroid ± anti-TNF (adalimumab, golimumab, infliximab+thiopurine preferred if treatment-naive), vedolizumab, tofacitinib/upadacitinib, or ustekinumab/guselkumab/mirikizumab/risankizumab | Continue the successful induction agent (except corticosteroid, methotrexate, cyclosporine, which never maintain) |
| Severe/fulminant, hospitalized | IV methylprednisolone 40-60 mg/day or hydrocortisone; if no response in 3-5 days, IV cyclosporine 2-4 mg/kg/day or infliximab | Transition survivors to thiopurine or vedolizumab (if induced with cyclosporine) or continue TNF-inhibitor/immunomodulator (if induced with infliximab) |
Topical mesalamine (enema/suppository) beats oralmesalamine or topical steroids for distal disease. Budesonide MMX is preferred over systemic corticosteroids when it's an option for moderate disease. When induction with corticosteroids works, hand off to a thiopurinefor maintenance since steroids can't do that job. Fulminant UC failing IV steroids gets 3-5 days, not weeks, before escalating to cyclosporine or infliximab. And critically: avoid switching a failed originator anti-TNF to its own biosimilar, switch to a different agent instead.
| Severity / location | Induction | Maintenance |
|---|---|---|
| Mild | Sulfasalazine 3-6 g/day (marginal efficacy; newer mesalamine derivatives even less effective in CD) | Consider treating as moderate-to-severe; 5-ASA agents are not preferred long-term |
| Small bowel (ileal/ascending colonic) | Budesonide CIR 9 mg/day, preferred first-line for this distribution | Can continue budesonide up to ~4 months; not indefinite |
| Perianal disease | Metronidazole up to 10-20 mg/kg/day ± infliximab | Anti-TNF-based maintenance |
| Moderate | Prednisone + infliximab, adalimumab, certolizumab, or vedolizumab ± methotrexate/azathioprine/mercaptopurine. Consider infliximab pre-surgery as a last option | Taper prednisone after 2-4 weeks; continue the biologic ± immunomodulator |
| Severe | Hydrocortisone 100 mg IV every 6-8 h; add azathioprine/mercaptopurine/methotrexate if not already on board; switch to natalizumab or vedolizumab if no response to anti-TNF + immunomodulator | Consider anti-TNF trough monitoring; ustekinumab as a last-line option |
Combining an anti-TNF agent with a thiopurine has become the preferred approach for moderate-to-severe CD, not because either alone is weak, but because the thiopurine reduces immunogenicity (antibody formation against the biologic), extending how long the biologic keeps working. This combination principle shows up again under therapy failure below.
Newer agents your course material adds beyond the classic handbook algorithm, now used across both diseases in moderate-to-severe disease unresponsive to first-line biologics: risankizumab, mirikizumab, and guselkumab(anti-IL-23), and upadacitinib(JAK inhibitor, CD-approved) alongside tofacitinib (UC-approved) and the S1P modulators ozanimod/estrasimod (UC-approved).
| Drug | Initial / Induction | Usual / Maintenance |
|---|---|---|
| 5-Aminosalicylates (mainly UC) | ||
| Sulfasalazine (Azulfidine) | 500 mg-1 g | 4-6 g/day (CD: 3-6 g/day) |
| Mesalamine (Asacol HD, Delzicol, Lialda, Pentasa, Apriso) | 1.2-2 g/day | 1.5-4.8 g/day (varies by formulation) |
| Mesalamine suppository (Canasa) | 1 g | 1 g daily to 3x weekly |
| Mesalamine enema (Rowasa) | 4 g | 4 g daily to 3x weekly |
| Olsalazine (Dipentum) | 1.5 g/day | 1.5-3 g/day |
| Balsalazide (Colazal) | 2.25 g/day | 2.25-6.75 g/day |
| Corticosteroids | ||
| Budesonide MMX (Uceris) - UC | 9 mg PO once daily | Up to 8 weeks, then taper |
| Budesonide CIR (Entocort EC) - CD | 9 mg PO once daily | Up to 8 weeks, then 6 mg/day up to 3 months |
| Budesonide rectal foam (Uceris) | 2 mg BID | 2 mg daily |
| Prednisone | 40-60 mg/day | Taper over 2-4 weeks; no maintenance role |
| Methylprednisolone / hydrocortisone (severe/toxic megacolon) | 40-60 mg/day IV or hydrocortisone 100 mg IV q6-8h | Induction only |
| Immunomodulators / immunosuppressants | ||
| Azathioprine (Imuran, Azasan) | 50-100 mg initial | 1-2.5 mg/kg/day |
| Mercaptopurine (Purinethol, Purixan) | 50-100 mg initial | 0.75-2.5 mg/kg/day |
| Methotrexate | 15-25 mg IM/SC weekly | Same, weekly (CD only) |
| Cyclosporine (rescue, severe UC) | 2-4 mg/kg/day IV | 2-8 mg/kg/day oral if transitioned |
| Anti-TNF-α (UC and CD except golimumab = UC only) | ||
| Infliximab (Remicade + biosimilars) | 5 mg/kg IV weeks 0, 2, 6 | 5-10 mg/kg IV every 8 weeks |
| Adalimumab (Humira + biosimilars) | 160 mg SC day 1, 80 mg day 15 | 40 mg SC every 2 weeks from day 29 |
| Certolizumab pegol (Cimzia) - CD only | 400 mg SC weeks 0, 2, 4 | 400 mg SC every 4 weeks |
| Golimumab (Simponi) - UC only | 200 mg SC wk 0, 100 mg wk 2 | 100 mg SC every 4 weeks |
| Anti-integrin | ||
| Vedolizumab (Entyvio) - UC and CD | 300 mg IV weeks 0, 2, 6 | 300 mg IV every 8 weeks |
| Natalizumab (Tysabri) - CD, refractory only | 300 mg IV | 300 mg IV every 4 weeks |
| Anti-IL-12/23 and anti-IL-23 | ||
| Ustekinumab (Stelara) - UC and CD | Weight-based IV: <55 kg 260 mg, 55-85 kg 390 mg, >85 kg 520 mg | 90 mg SC every 8 weeks |
| Risankizumab (Skyrizi) - UC | 1200 mg IV weeks 0, 4, 8 | 180-360 mg SC wk 12, then every 8 weeks |
| Risankizumab (Skyrizi) - CD | 600 mg IV weeks 0, 4, 8 | 180-360 mg SC wk 12, then every 8 weeks |
| Mirikizumab (Omvoh) - UC | 300 mg IV weeks 0, 4, 8 | 200 mg SC wk 12, then every 4 weeks |
| Mirikizumab (Omvoh) - CD | 900 mg IV weeks 0, 4, 8 | 300 mg SC wk 12, then every 4 weeks |
| Guselkumab (Tremfya) - UC and CD | 400 mg SC/IV weeks 0, 4, 8 | 100 mg SC every 8 weeks from wk 16 |
| JAK inhibitors | ||
| Tofacitinib (Xeljanz) - UC | 10 mg PO BID for 8 weeks (max 16 weeks) | 5 mg PO BID |
| Upadacitinib (Rinvoq) - UC and CD | Per product labeling | Per product labeling |
| S1P receptor modulators - UC only | ||
| Ozanimod (Zeposia) | 0.23 mg daily days 1-4, 0.46 mg daily days 5-7 | 0.92 mg daily from day 8 |
| Estrasimod (Velsipity) | Per product labeling | Per product labeling |
Upadacitinib and estrasimod doses are intentionally left as "per product labeling" here; neither source material gave exact mg values, and this deck won't guess at biologic/small-molecule dosing.
Sulfasalazineis a prodrug: a sulfonamide antibiotic (sulfapyridine) chemically bonded to mesalamine (5-ASA). Gut bacteria cleave the azo bond in the colon, releasing active mesalamine locally while the sulfapyridine moiety gets absorbed and causes most of the adverse effects (dose-related nausea, dyspepsia, headache, fatigue, plus rare but serious toxic epidermal necrolysis/SJS, pancreatitis, hepatitis, bone marrow suppression, interstitial nephritis, hemolytic anemia). Because it contains a sulfa moiety, it's contraindicated with true sulfa allergy.
Olsalazine and balsalazideuse the same diazo-bond strategy (two mesalamine molecules, or mesalamine plus an inert carrier) to deliver drug to the colon without the sulfa component, so they dodge the sulfa-allergy issue. Olsalazine's signature side effect is secretory diarrhea from the unabsorbed diazo compound in the small bowel.
Mesalamineformulations (Asacol HD, Delzicol, Lialda, Pentasa, Apriso) use pH-dependent or delayed/controlled-release coatings instead of a diazo bond, releasing the same active moiety at different points along the GI tract depending on formulation, which is why formulation choice matters for ileal vs colonic disease. Generally the best-tolerated of the group; rare but real risks include interstitial nephritis, pancreatitis, pericarditis, myocarditis, pneumonitis, and hypersensitivity.
Sulfasalazine inhibits folic acid absorption. Every patient on it needs oral folic acid supplementation, and it's an easy add-on to miss when you're focused on the GI symptoms.
Efficacy note:5-ASA agents work reasonably well in UC but have marginal-to-minimal efficacy in CD, and are not preferred for CD maintenance. This asymmetry trips people up because it's the same drug class treated very differently by disease.
Two targeted budesonide formulations exploit different release chemistry to hit different bowel segments: budesonide MMX (Multi-Matrix System, Uceris)is a pH-dependent tablet that delays release until the colon, used for mild-to-moderate UC. Budesonide CIR (Controlled Ileal Release, Entocort EC)is a controlled-release capsule that delivers drug to the terminal ileum, used for mild-to-moderate ileal/right-sided CD. Both undergo extensive first-pass hepatic metabolism via CYP3A4, giving low systemic bioavailability and fewer steroid-type side effects than systemic corticosteroids, but still real drug interaction potential with CYP3A4 inhibitors.
Systemic corticosteroids (prednisone 40-60 mg/day, or IV methylprednisolone/hydrocortisone for severe/fulminant disease) are used for moderate-to-severe active disease unresponsive to aminosalicylates, or when faster symptom control is needed. Adverse effects with any systemic use: hyperglycemia, hypertension, osteoporosis, acne, fluid retention, electrolyte disturbances, myopathy, muscle wasting, increased appetite, psychosis, infection risk, and adrenocortical suppression.
Corticosteroids have zero role in maintenancefor either UC or CD, they don't alter the long-term disease course and chronic use just accumulates toxicity. Always taper gradually over 2-4 weeks after remission, never stop abruptly (adrenal insufficiency/crisis risk), and always have a maintenance plan (5-ASA, thiopurine, biologic) ready before you start the taper.
Azathioprineand its active metabolite mercaptopurineimpair purine biosynthesis, halting DNA synthesis and inhibiting proliferation of activated immune cells. They're used for long-term maintenance in both diseases, generally reserved for patients who fail 5-ASA or are steroid-refractory/steroid-dependent, and they are not used to induce remissionin moderate-to-severe CD, only to maintain steroid-induced remission.
Efficacy and toxicity of thiopurines hinge on thiopurine methyltransferase (TPMT)activity (or NUDT15 phenotype). Rapid TPMT activityshunts metabolism toward 6-methylmercaptopurine (hepatotoxic, less effective) with lower 6-thioguanine (6-TGN). Normal activitygives a normal 6-TGN level. Intermediate activityraises 6-TGN, consider a 50% dose reduction. Minimal/poor activityproduces the highest 6-TGN and real bone marrow suppression risk, thiopurines are not recommendedhere. Therapeutic 6-TGN concentrations run 230-450 pmol per 8×10⁸ erythrocytes, though routine monitoring isn't available everywhere. Also watch the classic interaction: allopurinolblocks thiopurine metabolism and can precipitate severe toxicity.
Methotrexateis a folic acid analogue that inhibits dihydrofolate reductase, blocking purine and thymidine synthesis. Dosed 15-25 mg IM or SC once weekly (never daily, that's a fatal dosing error), it's an option for CD(not established for UC), reduces steroid dependency, and may substitute for thiopurines. Check a baseline pregnancy test before starting given its known effects on the fetus, and supplement folic acid to offset deficiency. Watch for bone marrow suppression, pancreatitis, pneumonitis/pulmonary fibrosis, hepatitis, GI upset, and CNS symptoms like fatigue and headache.
Cyclosporineinhibits calcineurin, blocking IL-2 and other stimulatory cytokine gene expression. Its role is narrow: short-term rescue in acute severe UCfailing IV corticosteroids, to avoid colectomy, dosed as a continuous IV infusion (2-4 mg/kg/day). It has little efficacy in CD. Not a maintenance drug, patients get bridged to a thiopurine or vedolizumab once stabilized.
Anti-TNF agents(infliximab, adalimumab, certolizumab, golimumab) bind and neutralize TNF-α, useful for moderate-to-severe active disease and for steroid-dependent or fistulizing disease, as both induction and maintenance. Infliximab is chimeric (part mouse, part human), adalimumab and golimumab are fully human, certolizumab is a humanized, pegylated Fab fragment. Chimeric agents carry more immunogenicity risk than fully human ones. Golimumab is not approved for CD in the US, UC only. All carry a boxed warning for increased risk of infections and malignancies; require TB testing and viral serology screening before starting; and can trigger infusion reactions (infliximab especially) or injection-site reactions.
Anti-integrin agentswork completely differently: vedolizumabblocks α4β7 integrin, preventing lymphocyte adhesion and migration specifically into gut tissue (gut-selective), approved for moderate-to-severe UC and CD, and notably not associated with PMLthe way natalizumab is. Natalizumabblocks integrins more broadly (not gut-selective) and carries a real risk of progressive multifocal leukoencephalopathy (PML), so it's reserved for CD unresponsive to other therapies, with brain MRI and mental status monitoring built into follow-up.
Anti-IL-12/23 and anti-IL-23-selective agents(ustekinumab targets the shared p40 subunit of IL-12 and IL-23; risankizumab, mirikizumab, and guselkumab selectively target IL-23's p19 subunit) block cytokines that drive Th1/Th17 activation of lymphocytes, approved across moderate-to-severe UC and CD. Watch for rare posterior reversible encephalopathy syndrome (PRES) with ustekinumab, and avoid live vaccines (especially BCG, 1 year before/after) with this whole class.
Biosimilars are not automatically swappable with each other or with the reference product. For infliximab, none of the current biosimilars (Inflectra, Avsola, Ixifi, Renflexis) are FDA-designated interchangeable with Remicade. For adalimumab, some are interchangeable (Cyltezo, Abrilada) while others (Amjevita, Hadlima) are not. Golimumab and certolizumab currently have no biosimilars. Always check the FDA Purple Bookbefore substituting, and remember the algorithm rule: if a patient fails an originator anti-TNF, don't just switch them to that same drug's biosimilar.
Tofacitinib(UC) and upadacitinib(UC and CD) inhibit Janus kinase signaling, blunting the intracellular signal transduction that activates the inflammatory response, given orally instead of by infusion or injection. Tofacitinib's monitoring burden is substantial and reflects real safety signals seen in trials: screen for baseline TB, don't start if lymphocytes <500/mm³, ANC <1000/mm³, or hemoglobin <9 g/dL, monitor lipids and LFTs every 4-8 weeks, watch for infection, thrombosis, lymphoma, and GI perforation (reported with the XR formulation), and check for drug interactions with CYP3A4/2C19 inhibitors. Avoid live vaccines with this class as well.
Ozanimodand estrasimodactivate sphingosine-1-phosphate (S1P) receptors, which traps lymphocytes in lymph nodes and blocks their movement to sites of gut injury, an oral, non-immunosuppressive-feeling mechanism that still carries real cardiac and ophthalmic monitoring requirements. Before starting ozanimod: baseline ECG, WBC, LFTs, ophthalmic exam, and varicella zoster antibody testing. It's contraindicated with a recent history (within 6 months) of MI, unstable angina, stroke/TIA, decompensated heart failure, Mobitz II or third-degree AV block, sick sinus syndrome, or with concomitant MAOI use, and requires effective contraception during and for 3 months after use in women of childbearing age given fetal risk. Watch for macular edema, changes in vision, heart rate/blood pressure changes, and respiratory symptoms.
This entire oral small-molecule group shares one theme: convenience of a pill instead of an infusion, traded for a monitoring checklist that's arguably heavier than some of the biologics.
Requires general supportive care, consideration of early surgery, and drug therapy together, not sequentially. Aggressive fluid and electrolyte correction for dehydration; blood transfusion if significant blood loss occurred; high-dose IV steroids(e.g., hydrocortisone 100 mg every 8 hours) to knock down acute inflammation; and broad-spectrum antimicrobialscovering gram-negative bacilli and intestinal anaerobes as preemptive therapy if perforation occurs or is suspected.
Fistulas are common in CD because the inflammation is transmural. Simple perianal fistulas can respond to metronidazole, sometimes combined with infliximab for more complex or refractory fistulizing disease.
Guidelines recommend reactive TDMfor anti-TNF agents (check trough level and antidrug antibodies when a patient is losing response) rather than routine trough checks on everyone, and routine TPMT testingbefore starting thiopurines to guide dosing.
| Failure pattern | Labs | What it means | What to do |
|---|---|---|---|
| Mechanistic failure | Adequate trough, no antibodies | Drug level is fine, the mechanism just isn't controlling this patient's disease | Switch to a different drug classentirely; staying within the same class won't help |
| Non-immune-mediated PK failure | Subtherapeutic trough, no antibodies | Drug is being cleared too fast, not being rejected | Increase dose or shorten the interval |
| Immune-mediated PK failure | Low/undetectable trough, high antidrug antibody titers | The immune system is neutralizing the drug | Switch to another drug within the same class(a different anti-TNF, not the same one's biosimilar) |
Pairing an anti-TNF with a thiopurine reduces the odds of immune-mediated PK failure by lowering antidrug antibody formation, which is the mechanistic reason combo therapy extends how long a biologic keeps working. It's not just "more immunosuppression is better," it's targeting a specific failure mode.
| Drug(s) | Watch for | Monitoring parameters |
|---|---|---|
| Sulfasalazine | N/V, headache, rash, anemia, pneumonitis, hepatotoxicity, nephritis, thrombocytopenia, lymphoma | Folate level, CBC, LFTs, SCr/BUN. Increase dose slowly over 1-2 weeks |
| Mesalamine | N/V, headache, GI disturbances | Generally minimal; watch renal function |
| Corticosteroids | Hyperglycemia, dyslipidemia, osteoporosis, hypertension, acne, edema, infection, myopathy, psychosis | BP, fasting lipid panel, glucose, vitamin D, bone density. Avoid long-term use or switch to budesonide |
| Azathioprine / Mercaptopurine | Bone marrow suppression, pancreatitis, lymphoma, liver dysfunction, rash, arthralgia | CBC, SCr/BUN, LFTs, TPMT/NUDT15 genotype-phenotype; may monitor 6-TGN |
| Methotrexate | Bone marrow suppression, pancreatitis, pneumonitis/pulmonary fibrosis, hepatitis | CBC, SCr/BUN, LFTs, baseline pregnancy test, chest x-ray |
| Infliximab / Adalimumab / Certolizumab / Golimumab | Infusion reactions (infliximab), infection, heart failure, optic neuritis, demyelination, injection site reaction | BP/HR with infliximab, neurologic exam/mental status, trough concentrations (infliximab), antidrug antibodies (all), baseline negative PPD and viral serologies |
| Natalizumab / Vedolizumab | Infusion reactions, PML (natalizumab only, not vedolizumab) | Brain MRI and mental status if natalizumab |
| Ustekinumab | Infections, skin cancers, rare PRES | S/S of infection, annual skin exam, avoid live vaccines |
| Tofacitinib | Infection, thrombosis, lymphoma, elevated cholesterol/CK/LFTs, cytopenias | S/S infection or thrombosis, baseline TB screen, lipids and LFTs every 4-8 weeks, avoid live vaccines |
| Ozanimod | Infection, bradyarrhythmia, hepatotoxicity, macular edema, fetal risk | Baseline ECG, WBC, LFTs, ophthalmic exam, VZV antibody testing, effective contraception |