What is the initial treatment approach for a newly diagnosed case of Crohn's disease?

Initial Treatment of Newly Diagnosed Crohn's Disease

For newly diagnosed Crohn's disease, treatment should be stratified by disease severity and location: mild ileal/ileocolonic disease starts with budesonide 9 mg daily, mild colonic disease with sulfasalazine 4-6 g/day, while moderate-to-severe disease requires early biologic therapy (infliximab or adalimumab) with or without immunomodulators rather than delaying for conventional therapy failure. 1

Disease Severity Assessment

Before initiating treatment, determine disease severity using a combination of:

• Clinical symptoms (abdominal pain, diarrhea frequency, weight loss) 1
• Objective inflammatory markers (C-reactive protein, fecal calprotectin) 1
• Endoscopic findings and imaging to assess extent and complications 1
• Risk factors for progression (young age at diagnosis, perianal disease, deep ulcerations, stricturing/penetrating behavior) 1

Mild Disease (Ileal or Ileocolonic Location)

First-line therapy: Budesonide 9 mg daily 1

• Budesonide is appropriate for isolated ileo-caecal disease with moderate activity, marginally less effective than prednisolone but with significantly fewer adverse effects 1
• Evaluate symptomatic response between 4-8 weeks to determine need for therapy modification 1
• Do not use budesonide for maintenance therapy beyond induction, as it is ineffective for long-term remission 1

Alternative for mild disease:

• Elemental or polymeric diets may induce remission in selected patients who have contraindications to corticosteroids or prefer to avoid them, though less effective than corticosteroids 1

What NOT to use:

• Oral 5-ASA (mesalazine) has no clear benefit over placebo for Crohn's disease and should not be used 1
• The ECCO guidelines explicitly recommend against 5-ASA for induction of remission in Crohn's disease 1

Mild Disease (Colonic Location Only)

First-line therapy: Sulfasalazine 4-6 g/day 1

• Sulfasalazine is effective for active colonic disease but has high incidence of side effects 1
• Evaluate symptomatic response between 2-4 months 1
• Topical mesalazine may be effective as adjunctive therapy for left-sided colonic disease of mild-to-moderate activity 1

Moderate-to-Severe Disease

First-line therapy: Early biologic introduction (infliximab or adalimumab) with or without immunomodulator 1

The 2021 AGA guidelines represent a paradigm shift from traditional step-up therapy:

• Early combination therapy (biologic + immunomodulator) achieves 61.5% corticosteroid-free remission at 52 weeks versus 42.2% with conventional step-up therapy 1
• At 24 months, early combination therapy reduces major adverse disease-related complications (hazard ratio 0.73) 1
• Delaying biologic therapy by using step-up approach with mesalamine/corticosteroids first may result in clinical harm from disease progression 1

Infliximab dosing (FDA-approved): 2

• Adults: 5 mg/kg IV at weeks 0,2, and 6, then every 8 weeks
• Some patients who initially respond may benefit from increasing to 10 mg/kg if they lose response 2

Adalimumab dosing (FDA-approved): 3

• Adults: 160 mg subcutaneous on Day 1 (single dose or split over 2 days), 80 mg on Day 15, then 40 mg every other week starting Day 29
• Azathioprine, 6-mercaptopurine, or methotrexate may be continued during biologic treatment if necessary 3

Alternative for moderate disease if biologics unavailable:

• Prednisone 40-60 mg/day for patients who failed budesonide or have more severe disease 1
• Evaluate symptomatic response between 2-4 weeks 1
• Never use corticosteroids for maintenance therapy - they are ineffective and associated with significant toxicity 1

Severe Disease Requiring Hospitalization

Intravenous corticosteroids: 1

• Hydrocortisone 400 mg/day or methylprednisolone 40-60 mg/day 1
• Concomitant IV metronidazole is advisable as it may be difficult to distinguish active disease from septic complications 1
• Evaluate symptomatic response within 1 week to determine need for therapy modification 1

Maintenance Therapy After Induction

For patients achieving remission on corticosteroids:

• Initiate thiopurine therapy (azathioprine 1.5-2.5 mg/kg/day or mercaptopurine 0.75-1.5 mg/kg/day) as steroid-sparing maintenance 1
• Thiopurines have slow onset (3-6 months) and should not be used as monotherapy for active disease 1

For patients on biologic therapy:

• Continue biologic maintenance dosing as per FDA labeling 3, 2
• Consider combination with immunomodulator for enhanced durability, though this increases infection risk 1

Critical Pitfalls to Avoid

• Never delay biologic therapy in moderate-to-severe disease by attempting mesalamine or prolonged corticosteroid trials first - this worsens long-term outcomes 1
• Never use oral 5-ASA (mesalazine) for Crohn's disease - multiple guidelines confirm lack of efficacy 1
• Never use corticosteroids for maintenance - they do not maintain remission and cause significant toxicity 1
• Never use thiopurines as monotherapy for active disease - onset of action is too slow (3-6 months) 1
• Do not use antibiotics as primary therapy except for perianal/fistulizing disease or suspected septic complications 1

Monitoring During Treatment

• Assess objective inflammatory markers (CRP, calprotectin) and endoscopic healing, not just symptoms 1
• Tight control with regular monitoring allows therapy adjustment to prevent disease progression 1
• Consider therapeutic drug monitoring for biologics to optimize dosing 4