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Source created 2026-08-25 · updated 2026-08-25
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ASCRS Ch46 - Medical Therapy for Crohn's Disease

Chapter 46, "Medical Therapy for Crohn's Disease," ASCRS Textbook of Colon and Rectal Surgery, 4th edition. Authors: Radhika K. Smith and Stefan D. Holubar. Book pp. 781–798 (title page through References).

Textbook reference chapter (not primary literature), Part IV/benign-and-miscellaneous material. Substantial overlap with Crohn Disease's existing BSG 2025-guideline-sourced "Advanced therapy, monitoring, and post-surgical management" section, but adds real primary-trial-level detail that section didn't have: named trials for combination therapy (SONIC, REACT/REACT2, DIAMOND), a treat-to-target framework (STRIDE, CALM), three separate TDM trials with genuinely conflicting results (TAXIT, TAILORIX, PAILOT), biosimilar non-inferiority data, and postoperative-recurrence risk factors (histologic margin status, plexitis). Also covers microbiome-directed therapies (antibiotics, diet, fecal transplant) essentially absent from the wiki until now, and a notable patient-safety flag (2020 FDA fecal-transplant safety alert).

Structure

  • Microbiome therapies: antibiotics (2011 meta-analysis RR 0.85 vs. placebo in active CD, p=0.03, but high heterogeneity precluded firm conclusions; 2019 Cochrane update of 13 RCTs found modest benefit not clinically significant on moderate-to-high-quality evidence; ACG/ECCO do not recommend for induction or maintenance); probiotics (multiple meta-analyses show ineffective for CD induction/maintenance and possibly not without risk); dietary interventions (Cochrane meta-analysis of 18 RCTs/1878 patients — heterogeneous, low-quality evidence, no firm conclusions despite some signal for symptom-based/restrictive diets); fecal transplant (17-patient pilot RCT in steroid-induced-remission CD patients — no primary efficacy endpoint met, though endoscopic scores/CRP improved; a meta-analysis suggests possible efficacy in UC but not Crohn's; 2020 FDA Safety Alert — 2 patients with chronic medical conditions died of complications from FMT-transmitted enteropathogenic/shigatoxin-producing E. coli); exclusive enteral nutrition (EEN — full-liquid mono-diet, well-established pediatric efficacy, adult use mainly during steroid taper pending elective surgery).
  • 5-ASA Therapy: limited role in CD given its mucosal (vs. Crohn's full-thickness) mechanism of action; RCTs/meta-analyses show no efficacy for induction of remission (ileal, ileocolic, or colonic disease) or maintenance (ECCO meta-analysis RR 1.03); possible role in isolated colonic CD (older NCCDS/ECCDS trials, mixed results, lacking modern endoscopic/biochemical endpoints) and Crohn's proctitis (rectal 5-ASA formulations for disabling urgency/tenesmus/agoraphobia — 500– 1000mg suppository at bedtime, 4g/60cc enema 1–2x/day).
  • Corticosteroids: topical budesonide (3mg capsule dosed up to 9mg/day; "open-capsule technique" — half a 3mg capsule opened and sprinkled on food — to target small bowel proximal to the terminal ileum; MMX® formulation for colonic release; Cochrane meta-analysis confirms efficacy vs. placebo but inferiority to conventional steroids; Table 46.3 long-term side effects); systemic corticosteroids (NNT 3 for induction per a 267-patient meta-analysis; Table 46.4 glucocorticoid conversion table; Table 46.5 toxicity by organ system; Table 46.6 adrenal suppression/Addisonian crisis signs; practical tapering — reduce dose 50% every 5–7 days, slower taper with additional weeks if prolonged prior steroid exposure).
  • Immunomodulators: thiopurines (TP pharmacokinetics — AZA/6-MP → 6-thioguanine via TPMT; ~80% normal TPMT metabolizers, ~10% hyperactive "shunters" (increased hepatotoxicity risk, managed with low-dose allopurinol co-prescription), ~10% heterozygous/intermediate activity (need higher dose), 0.3% homozygous-deficient (will not respond, high myelosuppression risk); Table 46.7 side effects by frequency/testing method; EBV status caveat: young men with +EBV status carry a small but demonstrable risk of hepatocellular T-cell lymphoma (universally fatal) on thiopurine therapy — a distinct, genuinely new safety consideration from the wiki's existing TPMT-focused content); methotrexate (Table 46.8 side effects by organ system with mitigation strategies — folate co-prescription, dose caps, GFR monitoring, contraception).
  • Biologic Therapy: TNFi dosing detail (Table 46.9 — infliximab, adalimumab, certolizumab pegol, natalizumab, vedolizumab, route/induction/maintenance doses); combination therapy trial evidence — SONIC trial (infliximab+azathioprine vs. either alone: mucosal healing RR 1.82, clinical remission benefit at 26 weeks, lower serious adverse events RR 0.56); REACT/ REACT2 trials (early combined immunosuppression vs. conventional step-up: REACT found lower complication rates but no steroid-free-remission difference; REACT2 ongoing, mucosal-healing primary endpoint); DIAMOND trial (adalimumab+thiopurine vs. adalimumab alone: not superior for remission [RR 0.95] though endoscopic improvement was better at week 26 [RR 1.32] — benefit lost by 1 year; lower AZA dose than typical CD practice, a caveat on generalizability); leukocyte- trafficking agents (natalizumab PML risk quantified — up to 1 in 100 JC-virus-antibody-positive patients; vedolizumab has no PML risk given gut selectivity); interleukin-12/23 antagonist (ustekinumab); biosimilars (a 220-patient non-inferiority RCT of infliximab-dyyb vs. originator infliximab with a treatment-switch design: week-6 response rates 69.4% vs. 74.3%, establishing non-inferiority; limited data on biosimilar-to-biosimilar switching).
  • Induction and Maintenance of Remission: mild/moderate/severe disease-specific induction algorithms (by location — terminal ileum, colon, upper GI); target-to-treat framework — genuinely new structural concept for the wiki: STRIDE (Selecting Therapeutic Targets in IBD) defines treatment targets as resolution of symptoms/altered bowel habit plus endoscopic remission (absent ulceration) or MRE/CTE-defined resolution of inflammation, assessed at 3-month (patient-reported) and 6–9-month (endoscopic) intervals; CALM trial (tight-control strategy — escalate on CDAI>150 + fecal calprotectin>250 + CRP>5 — vs. symptom-driven care: superior endoscopic remission and lower CD-related hospitalization with tight control); therapeutic drug monitoring — three trials with genuinely mixed results: TAXIT (263 patients, dose-adjust to target trough 3–7μg/mL vs. empiric dosing: no effect on 1-year clinical remission, but fewer flares and a 28% cost reduction), TAILORIX (122 biologic-naive patients, three dose- intensification strategies vs. symptom-guided control arm: no benefit of TDM over symptom-guided management at 1 year — underpowered, low control-arm escalation threshold flagged as a limitation), PAILOT (78 pediatric patients, proactive vs. reactive adalimumab TDM: proactive significantly better); reactive-TDM algorithm (Fig. 46.2 — drug level + antidrug antibody decision tree, same structure as the wiki's existing BSG-sourced version); de-escalation framework (Fig. 46.3 — confirmation of deep remission via biomarkers/endoscopy/imaging before de-escalating, then structured post-de-escalation surveillance); postoperative prophylaxis — 90% endoscopic and 60% clinical recurrence by 3 years off medical therapy, 50% needing additional surgery within 10 years; the only RCT on prophylaxis timing (routine azathioprine at 8 weeks vs. endoscopically-guided therapy at 6–12 months) found no difference but had substantial methodologic flaws (mismatched cohorts, low accrual, high attrition); a recent meta-analysis found histologically positive margins (OR 1.7) and plexitis (OR 2.3) significantly increase postoperative recurrence risk — genuinely new, surgically actionable risk factors; probiotics, 5-ASA, and budesonide show no benefit over placebo for postoperative prophylaxis across numerous RCTs (extends the wiki's existing "5-ASA/purine analogue monotherapy not suggested" note to these additional agents); early/aggressive prophylaxis particularly important in patients with recurrence risk factors (younger age, male sex, smoking, penetrating/fistulizing disease, prior surgery, short disease duration).

Open items / gaps

  • Every named trial in this chapter (SONIC, REACT/REACT2, DIAMOND, CALM, TAXIT, TAILORIX, PAILOT, the infliximab-dyyb non-inferiority RCT, the FMT pilot RCT) is cited at the textbook/secondary level only — see Crohn Disease's own Open items for what would be highest-value to independently ingest. TAXIT vs. TAILORIX's disagreement on whether TDM improves outcomes is a genuinely contested question the wiki should flag rather than resolve.
  • Chapter 47 ("Anorectal Crohn's Disease," Steinhagen E, Bafford AC) begins next — its opening framing (fistulizing-complications epidemiology, general management principles: control sepsis, treat underlying luminal disease, avoid steroids/surgery in inactive or asymptomatic disease) was visible in this read but not yet ingested; likely a substantial reconciliation target against the wiki's existing perianal-Crohn's content scattered across Crohn Disease and the ASCRS Ch13/ Ch14/Ch15 fistula pages.