Pharmacologic management of luminal Crohn’s disease in adults is stratified by disease severity (mild-to-moderate, moderate-to-severe, severe/fulminant), risk of progression, and prior exposure to advanced therapy. Treatment has two phases: induction of remission and maintenance of remission. Current guidelines have moved away from the historical “step-up” sequence (aminosalicylates → corticosteroids → immunomodulators → biologics) toward early advanced therapy in moderate-to-severe or high-risk disease, with a treat-to-target goal of steroid-free clinical and endoscopic remission rather than symptom control alone.^[1][2][3] Budesonide is first-line for mild ileocecal disease; oral mesalamine is not recommended. Corticosteroids induce but do not maintain remission. Hospitalized patients with severe disease receive intravenous corticosteroids, with early consideration of infliximab and surgical consultation. Perianal fistulizing disease, surgery, nutrition, and diagnostics are covered in separate microchapters.

Sources: ACG 2025, AGA 2025, JAMA 2026.^[1][2][3]

• Budesonide (controlled ileal-release, 9 mg once daily) is recommended to induce symptomatic remission in mild-to-moderate ileocecal or right-colonic disease (ACG: strong recommendation, moderate-quality evidence).^[1]
  • Extensive first-pass hepatic metabolism limits systemic effects.
  • In a 258-patient RCT, 8-week remission was 51% with budesonide vs 20% with placebo.^[4] Benefit was attenuated at 3 months in pooled analyses.^[3]
  • Not recommended for maintenance (ACG: strong recommendation, low-quality evidence). Taper and stop by approximately 3 months.^[1][3]
• Sulfasalazine (3–6 g/day in divided doses) may modestly induce symptomatic remission in mild colonic or ileocolonic disease. It is not effective for isolated small-bowel disease or for mucosal healing.^[1][5]
• Oral mesalamine (5-ASA) is not recommended for induction or maintenance (ACG: strong recommendation, moderate-quality evidence).^[1]
  • Meta-analytic data show no benefit over placebo for remission or mucosal healing, and topical 5-ASA is of limited benefit.^[1][6]
  • Despite this, 5-ASA remains widely prescribed in Crohn’s disease and represents low-value care.^[6]
  • Possible exception (low-quality evidence): high-dose mesalamine for induction in selected patients with mild luminal disease who wish to avoid corticosteroids.^[6]
• Dietary therapy: Exclusive enteral nutrition for 6–8 weeks is first-line induction in children. The Crohn’s disease exclusion diet, Mediterranean diet, and similar regimens may support induction or maintenance in low-risk mild disease.^[7]
• Monitor closely for progression; many patients with mild disease eventually require escalation.^[5]

Advanced therapy, with or without an immunomodulator, is recommended for induction and maintenance in moderate-to-severe disease (generally CDAI ≥220).^[1][2]

• The AGA suggests initial advanced therapy over step therapy with corticosteroids and/or immunomodulators.^[2][8]
• In the open-label PROFILE trial of 386 newly diagnosed patients, top-down infliximab plus immunomodulator achieved far higher sustained steroid-free and surgery-free remission at 1 year than accelerated step-up therapy (79% vs 15%).^[9][3]

Sources: ACG 2025, AGA 2025.^[1][2]

Labeled anti-TNF induction regimens:^[10]

• Infliximab: 5 mg/kg IV at weeks 0, 2, and 6, then every 8 weeks.
• Adalimumab: 160 mg SC at week 0 and 80 mg at week 2, then 40 mg every other week.
• Certolizumab pegol: 400 mg SC at weeks 0, 2, and 4, then every 4 weeks.

• Advanced-therapy–naïve: The AGA suggests a higher-efficacy agent (infliximab, adalimumab, vedolizumab, ustekinumab, risankizumab, mirikizumab, or guselkumab) over a lower-efficacy agent (certolizumab pegol or upadacitinib).^[2][11] Vedolizumab is more efficacious in naïve than in exposed patients.^[11]
• Advanced-therapy–exposed: Risankizumab, guselkumab, upadacitinib, and adalimumab are highly effective and may outperform vedolizumab and mirikizumab. Risankizumab and guselkumab are favored over ustekinumab and vedolizumab.^[11][3]
• Individualize choice by phenotype (stricturing, penetrating, perianal), extraintestinal manifestations, route preference, comorbidities and safety profile, and access.^[3][5]

• A thiopurine or methotrexate combined with an anti-TNF agent is suggested over anti-TNF monotherapy for induction and maintenance. Combination therapy lowers immunogenicity and improves drug levels.^[8]
• The 2025 AGA living guideline makes no recommendation for adalimumab combined with an immunomodulator, or for infliximab combined with methotrexate, over monotherapy.^[2]
• There is no recommendation for combining immunomodulators with non-TNF biologics.^[8]

Sources: AGA 2025, ACG 2025.^[2][1]

• Natalizumab: carries a risk of progressive multifocal leukoencephalopathy. Reserve for refractory cases with negative anti-JCV antibody.^[8]
• Thiopurine monotherapy for induction.^[2]
• Corticosteroids for maintenance.^[8]
• Mesalamine for induction or maintenance.^[1]

• Hospitalize. Give IV corticosteroids (methylprednisolone 40–60 mg/day or equivalent) while steroid-sparing therapy is planned.^[1]
• Supportive care:^[12]
  • IV fluid resuscitation.
  • Venous thromboembolism prophylaxis from admission.
  • Nutritional and electrolyte correction.
  • Avoid antidiarrheals, opioids, and anticholinergics.
  • Exclude C. difficile and cytomegalovirus.
• Infliximab is effective in severe disease and can be given in hospital. Its weight-based dosing provides higher drug exposure, which may be advantageous with high inflammatory burden. Efficacy of adalimumab and certolizumab in this setting is less certain.^[1]
• Failure to improve within about 3–7 days of IV corticosteroids, with or without rescue anti-TNF therapy, should prompt early surgical consultation.^[12]
  • Subtotal colectomy with end ileostomy is standard for medical failure or colitis emergencies (perforation, toxic megacolon, uncontrolled hemorrhage).^[12]

• Screen for latent tuberculosis and hepatitis B before starting biologic therapy. Manage positive results with specialist input before treatment.^[10]
• Update vaccinations before starting immunosuppression.^[10]
• Avoid anti-TNF agents in:^[10]
  • Untreated latent tuberculosis.
  • Demyelinating disease or optic neuritis.
  • Moderate-to-severe heart failure.

• Budesonide is preferred over prednisone for mild ileocecal disease because of its safety profile. Neither drug is a maintenance therapy.^[1]
• Anti-TNF plus immunomodulator outperforms anti-TNF monotherapy largely by reducing antidrug antibodies and raising drug levels.^[8]
• Treating Crohn’s disease like ulcerative colitis with mesalamine is ineffective and low-value.^[6]
• Prolonging corticosteroids as de facto maintenance causes cumulative toxicity.^[3]
• Thiopurines do not induce remission.^[2]
• Omitting TPMT/NUDT15 testing before thiopurines risks severe myelosuppression.^[1]
• Delaying surgical consultation in steroid-refractory severe colitis is a common error.^[12]