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Source created 2026-08-25 · updated 2026-08-25
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ASCRS Ch45 - Medical Management of Ulcerative Colitis

Chapter 45, "Medical Management of Ulcerative Colitis," ASCRS Textbook of Colon and Rectal Surgery, 4th edition. Authors: Amy L. Lightner and Scott A. Strong. Book pp. 765–779 (title page through References).

Textbook reference chapter (not primary literature), Part IV/benign-and-miscellaneous material. Heavily overlapping/reconciliation chapter: Ulcerative Colitis already carries a detailed medical-management section sourced from two 2025/2024 society guidelines (ACG 2025 - Ulcerative Colitis Guideline, AGA 2024 - Moderate-to-Severe UC Pharmacotherapy Guideline), so most of this chapter's content (advanced-therapy roster, VARSITY head-to-head data, ASUC escalation algorithm) was already present nearly verbatim. Genuinely new material: homeopathic/ adjunct agents (curcumin), drug-mechanism and formulation detail, concrete pivotal-trial dosing/ response tables (Tables 45.4–45.5), a dedicated maintenance-of-remission framework, and CONSTRUCT-trial/biosimilar rescue-therapy detail for ASUC.

Structure

  • Homeopathic agents: curcumin (mechanism — NF-κB suppression, Th1/Th2 cytokine modulation, anti-IL-1/anti-TNF properties; meta-analysis of 7 studies/380 patients — threefold increase in clinical/endoscopic response as adjunct to mesalamine, 21 mostly-mild adverse events); probiotics (meta-analysis suggests bifidobacteria-containing probiotics show promise for active UC, not FDA-approved for any indication).
  • 5-ASA compounds: mechanism (activates PPAR-γ nuclear receptors controlling apoptosis/cell proliferation/inflammation/metabolic function, high expression in colon epithelial cells partly gut-bacteria-stimulated); formulation-dependent colonic delivery (bacterial-, pH-, and time- mediated release); sulfasalazine (5-ASA bound to sulfapyridine, cleaved by colonic bacteria) vs. mesalamine (derivative formulations) side-effect comparison — sulfasalazine's sulfapyridine moiety carries a wider range of serious adverse events (GI upset, headache, bone marrow suppression, fever, hemolytic anemia, hepatitis, hypersensitivity, pancreatitis, pneumonitis, rash; requires concomitant folic acid 1 mg/day since the drug depletes folate stores) vs. mesalamine's cleaner profile (rare interstitial nephritis, routine renal monitoring recommended).
  • Glucocorticoids: mechanism (modulates immune response, inhibits adhesion-molecule expression, decreases inflammatory-cell trafficking); budesonide's extensive first-pass hepatic metabolism rationale; three budesonide formulations (two standard capsules releasing in terminal ileum/right colon, newer budesonide MMX® releasing throughout the entire colon); dose/duration- dependent side effects (striae, acne, cataracts, fluid retention, glaucoma, hyperglycemia, hypertension, insomnia, mood disturbance, moon facies, weight gain, myopathy, osteonecrosis, osteoporosis, adrenal suppression).
  • Immunomodulators: thiopurines (mechanism, TPMT genotyping detail, pancreatitis timing — typically first 8 weeks, should not be rechallenged after pancreatitis — CBC monitoring at 1–2 week intervals initially then ≥3-monthly, serious-infection signal from a 6273-patient cohort — adjusted OR 1.23, 95% CI 0.96–1.57, 10 more serious infections per 1000 patients); methotrexate (oral 12.5–15 mg or IM/SC 25 mg weekly; GI upset/stomatitis most common side effects; rare hepatic fibrosis, hypersensitivity pneumonitis); calcineurin inhibitors (cyclosporine/tacrolimus dosing by infusion vs. oral route; 13.5% discontinuation rate for GI intolerance/hypertension in one cohort).
  • JAK inhibitors: tofacitinib dosing (10 mg BID initial, 5 mg BID maintenance given the ORAL SURVEILLANCE-derived VTE/clot signal at the higher dose); infection/hyperlipidemia risk; no immunogenicity concern (small molecule, not biologic).
  • Biologic agents/biosimilars: anti-TNF dosing detail (infliximab 5 mg/kg q8wk, dose-escalatable to 10 mg/kg or q6wk; adalimumab 40 mg q2wk after induction; golimumab 100 mg q4wk after induction); vedolizumab (300 mg, gut-selective α4β7 integrin blocker, favorable safety profile across a 2830-patient pooled RCT analysis); ustekinumab (weight-based induction, 90 mg SC q8wk maintenance); VARSITY trial (vedolizumab vs. adalimumab, moderate-to-severe UC: week-52 clinical remission 31.3% vs. 22.5% [p=0.006], endoscopic improvement 39.7% vs. 27.7% [p<0.001] — same numbers already cited via ACG 2025 - Ulcerative Colitis Guideline/ AGA 2024 - Moderate-to-Severe UC Pharmacotherapy Guideline on Ulcerative Colitis, now a third independent secondary citation); UC-SUCCESS combination-therapy data (already in wiki via AGA 2024); Table 45.4 (pivotal induction trials — ACT 1/2, ULTRA 1/2, PURSUIT-SC, GEMINI 1, UNIFI, OCTAVE 1/2, with randomized patient counts and response rates by dose) and Table 45.5 (pivotal maintenance trials, same structure).
  • Disease severity: Truelove and Witts score (Table 45.1 — 6 criteria: defecation frequency, bloody stool, fever, tachycardia, anemia, ESR); Mayo score system (Table 45.2 — 4 domains: stool frequency, rectal bleeding, endoscopy, physician global assessment, each 0–3); Mayo endoscopic severity score (Table 45.3, same 0–3 grading already ingested from ASCRS Ch44).
  • Induction of remission: mild-to-moderate algorithm (topical vs. oral 5-ASA thresholds, budesonide MMX dose-finding RCT results — 17.9%/13.2%/12.1%/7.4% remission at 9mg/6mg/5-ASA/ placebo — statistical significance only at the higher budesonide dose); moderate-to-severe algorithm (5-ASA largely ineffective at this severity; systemic glucocorticoids remain the induction cornerstone; immunomodulator monotherapy not recommended by ACG/AGA for induction given insufficient MERIT-UC-era evidence; biologic/JAK-inhibitor induction is the default).
  • Severe/fulminant disease (ASUC): definition (already ingested from Ch44); IV glucocorticoid efficacy data (open-label series: 73% remission by day 5, 47% maintained, 18% required surgery; larger systematic review of 32 studies/1948 patients: 67% mean response rate, 27% requiring colectomy; no benefit above 60mg/day dose-finding); cyclosporine RCTs (2 mg/kg/day found equivalent to 4 mg/kg/day and now the recommended ASUC dose — refines the wiki's existing "2–4 mg/kg" range); cyclosporine-vs-infliximab RCT (115 patients, similar treatment-failure and 1/5-year colectomy-free survival rates) and the CONSTRUCT trial (quality-of-life/healthcare- cost comparison, no difference in quality-adjusted survival, colectomy frequency/timing, or adverse events including mortality) — genuinely new to the wiki; sequential salvage therapy (infliximab after cyclosporine failure or vice versa) carries a significant colectomy rate (up to 60% at 1 year) and is "not generally recommended"; biosimilar CT-P13 rescue-therapy studies (63- and 83-patient cohorts, comparable efficacy/mucosal-healing/colectomy-free-survival to originator infliximab).
  • Maintenance of remission: which patients don't need ongoing therapy (isolated proctitis, <1 flare/year, topical-mesalamine-responsive); 5-ASA maintenance dosing/evidence (7-trial meta-analysis for proctitis, 11-trial meta-analysis for left-sided/extensive disease; standard- to-high-dose superior to low-dose, formulation not predictive of relapse); budesonide MMX not studied for maintenance; glucocorticoids explicitly not recommended for maintenance (taper over 8–12 weeks instead); thiopurines effective for maintenance (4 placebo-controlled + 3 5-ASA-comparison trials); methotrexate NOT superior to placebo for maintenance (2 RCTs incl. the US-based MERIT-UC trial: 66% relapse on methotrexate vs. 63% on placebo) — AGA does not recommend methotrexate monotherapy for maintenance; tofacitinib maintenance data (52-week remission 34.3%/40.6%/11.1% at 5mg/10mg/placebo, no increased VTE at either dose but increased herpes zoster at 10mg); biologic maintenance data (anti-TNF class superior to placebo, no single agent superior to another; vedolizumab superior to placebo, 40% vs. 16% maintained remission in induction-responders; ustekinumab similarly superior); biosimilar-switching studies (CT-P13 switch from infliximab: no changes in disease activity/CRP/hemoglobin/fecal calprotectin/drug-antibody levels at 6 months in one study; cost-effective per an 8-study, 594-patient meta-analysis; a multicenter cohort study also confirmed long-term mucosal healing at week 54 post-switch).

Open items / gaps

  • Every named trial in this chapter (VARSITY, UC-SUCCESS, CONSTRUCT, MERIT-UC, GEMINI, UNIFI, ACT 1/2, ULTRA 1/2, PURSUIT-SC, OCTAVE 1/2, the CT-P13 biosimilar-switch studies) is cited at the textbook/secondary level only — see Ulcerative Colitis's own Open items and Research Priorities for what would be highest-value to independently ingest. VARSITY in particular is now cited by three independent secondary sources (ACG 2025, AGA 2024, this chapter) with identical numbers, which raises confidence in the figure but still isn't a primary read of the trial itself.
  • Chapter 46 ("Medical Therapy for Crohn's Disease," Smith RK, Holubar SD) begins next — its opening framing (AGA/ACG/ECCO Crohn's guideline summary Table 46.1, high-risk-feature Table 46.2) was visible in this read but not yet ingested; likely another significant reconciliation target, this time against Crohn Disease's existing BSG 2025-guideline-sourced advanced-therapy section — worth checking for agreement/disagreement given three different Crohn's-specific guidelines (AGA, ACG, ECCO) are named here vs. the wiki's current single-guideline (BSG) basis.