What is the recommended treatment plan for an adult with Crohn’s disease, including induction and maintenance therapy based on disease location, severity, prior therapy, and complications?

Treatment for Crohn's Disease

For adults with moderate to severe Crohn's disease, initiate anti-TNF therapy (infliximab or adalimumab) in combination with a thiopurine as first-line treatment for both induction and maintenance of remission. 1

Disease Severity Classification

Before selecting therapy, classify disease severity:

• Moderate to severe disease is defined by a CDAI score ≥220 OR high risk of adverse complications (surgery, hospitalization, disability) based on structural damage, inflammatory burden, and quality of life impact 1
• This classification determines whether biologic therapy is indicated versus less aggressive approaches

First-Line Therapy for Moderate to Severe Luminal Disease

Biologic-Naïve Patients

Preferred regimens (in order of recommendation strength):

• Infliximab 5 mg/kg IV at weeks 0,2, and 6, then every 8 weeks PLUS azathioprine or 6-mercaptopurine 1, 2, 3
• Adalimumab 160 mg SC, then 80 mg at week 2, then 40 mg every 2 weeks PLUS methotrexate 1, 4
• Ustekinumab (strong recommendation, moderate certainty evidence) 1

The AGA recommends infliximab, adalimumab, or ustekinumab OVER certolizumab pegol for biologic-naïve patients based on superior efficacy data 1. Infliximab and adalimumab have moderate certainty evidence (RR 0.54 and 0.82 for induction respectively), while certolizumab pegol has only low certainty evidence and failed to meet the minimal clinically important difference threshold 1.

Combination Therapy is Critical

Do not use biologic monotherapy when initiating infliximab. Combination with thiopurines (azathioprine or 6-mercaptopurine) is strongly recommended based on moderate-quality evidence, as it prevents antibody formation and improves efficacy 2. For adalimumab, combination with methotrexate may be more effective than monotherapy, though evidence is less robust 4.

Alternative First-Line Options

• Vedolizumab is suggested over no treatment (conditional recommendation) but is suggested over certolizumab pegol for patients prioritizing safety profile over speed of action 1, 4
• Vedolizumab has low certainty evidence for induction but moderate certainty for maintenance 1

Avoid Natalizumab

The AGA suggests AGAINST natalizumab due to risk of progressive multifocal leukoencephalopathy (PML), despite efficacy data (RR 0.88 for induction, 0.58 for maintenance) 1. Only consider in JC virus antibody-negative patients who will adhere to ongoing monitoring and place high value on potential benefits 1

Response Assessment Timeline

Evaluate clinical response between weeks 8-12 after initiating induction therapy. 2, 4 Patients who do not respond by week 14 are unlikely to respond with continued dosing and should be switched to alternative therapy 3.

For patients on infliximab who initially respond but lose response, consider increasing dose to 10 mg/kg 3.

Second-Line Therapy After Anti-TNF Failure

Primary Non-Response (Never Responded)

Ustekinumab is strongly recommended (strong recommendation, moderate certainty evidence) 1, 4. Vedolizumab is suggested as an alternative 1, 4.

Secondary Non-Response (Lost Response)

• If failed infliximab: Switch to adalimumab or ustekinumab (conditional recommendation, low certainty evidence) 1
• If failed adalimumab: Consider infliximab or ustekinumab based on indirect evidence 1, 4

Perianal Fistulizing Disease

For active perianal disease without abscess:

• Infliximab is strongly recommended for induction and maintenance of fistula remission (strong recommendation, moderate certainty evidence) 1
• Use biologic agents EARLY rather than delaying until after failure of 5-aminosalicylates or corticosteroids (conditional recommendation, low certainty evidence) 1
• Combine biologic with antibiotics for induction of fistula remission (strong recommendation, moderate certainty evidence) 1
• Do NOT use antibiotics alone for fistula remission (strong recommendation against) 1

Role of Corticosteroids

Corticosteroids are NOT recommended for maintenance of remission (strong recommendation against) due to significant side effects including bone loss, metabolic complications, increased intraocular pressure, and infection risk 1, 4.

For acute induction in patients who failed budesonide, prednisone 40-60 mg/day may be used, with response assessment at 2-4 weeks 4.

Role of Immunomodulators

Thiopurines (Azathioprine, 6-Mercaptopurine)

• Do NOT use as monotherapy for induction (conditional recommendation against, very low certainty evidence) 1, 4
• May use for maintenance in patients who achieved corticosteroid-induced remission (conditional recommendation, low certainty evidence) 1, 4
• Essential component of combination therapy with infliximab 2

Methotrexate

• Parenteral (SC or IM) methotrexate is suggested for induction and maintenance (conditional recommendation, moderate certainty evidence) 1, 4
• Oral methotrexate is NOT recommended due to limited efficacy 1, 4

Mild Disease Management

For the estimated 20-30% of patients with mild disease and low risk of progression 5:

• Budesonide for mild ileal or ileocolonic disease 5, 6
• Sulfasalazine for colonic disease (other aminosalicylates have no role) 5, 6
• Close clinical monitoring is appropriate for select low-risk patients 5

Common Pitfalls to Avoid

• Do not delay combination therapy: Starting thiopurines concurrently with infliximab prevents antibody formation from the outset 2
• Do not use corticosteroids for maintenance: They are ineffective and cause significant harm 1, 4
• Do not continue ineffective therapy beyond 14 weeks: Switch to alternative mechanism if no response 3
• Do not use thiopurine monotherapy for induction: It is ineffective for achieving remission 1, 4
• Do not use oral methotrexate: Only parenteral formulations are effective 1, 4