What is the recommended infliximab (Infliximab) induction regimen for patients with moderate to severe Crohn's disease?

Infliximab Induction Regimen for Moderate to Severe Crohn's Disease

Administer infliximab 5 mg/kg intravenously at weeks 0,2, and 6 for induction therapy in patients with moderate to severe Crohn's disease. 1, 2

Standard Induction Dosing

• The FDA-approved induction regimen is 5 mg/kg IV at weeks 0,2, and 6, followed by maintenance dosing every 8 weeks thereafter 2
• This three-dose induction strategy at 0,2, and 6 weeks is the preferred approach for inducing remission, as it optimizes early response rates 3
• The 5 mg/kg dose should not be adjusted during induction; dose escalation to 10 mg/kg is reserved only for patients who initially respond but subsequently lose response during maintenance therapy 2

Combination Therapy Recommendation

Infliximab should be started in combination with a thiopurine (azathioprine or 6-mercaptopurine) for induction in biologic-naïve patients with moderate to severe Crohn's disease. 1

• The ECCO guidelines provide a strong recommendation for combination therapy with thiopurines when initiating infliximab, based on moderate-quality evidence 1
• The landmark SONIC trial demonstrated that combination therapy with infliximab plus azathioprine achieved corticosteroid-free remission in 56.8% of patients at week 26, compared to 44.4% with infliximab monotherapy (p=0.02) 4
• Combination therapy also improved mucosal healing rates: 43.9% with combination versus 30.1% with infliximab alone (p=0.06) 4
• The AGA suggests combination therapy over monotherapy, though notes the evidence certainty is very low; they acknowledge that combination with methotrexate may also be effective based on indirect evidence 1

Rationale for Combination Therapy

• Concomitant immunosuppression reduces the formation of antibodies to infliximab (human anti-chimeric antibodies), which decreases the risk of infusion reactions and loss of response 3
• The combination approach reduces acute infusion reactions and delayed hypersensitivity-like reactions 3
• Serious infection rates were similar between combination therapy (3.9%) and infliximab monotherapy (4.9%) in the SONIC trial, suggesting acceptable safety 4

Response Assessment and Decision Points

• Evaluate clinical response between weeks 8-12 after initiating induction therapy 5
• Patients who do not respond by week 14 are unlikely to respond with continued dosing and should be switched to an alternative biologic 2
• The ACCENT I trial demonstrated that 58% of patients respond to a single infusion within 2 weeks, establishing the expected early response rate 6

Clinical Context and Positioning

• Infliximab is recommended as first-line therapy for moderate to severe Crohn's disease, particularly in patients with risk factors for poor prognosis 5
• The ECCO guidelines provide a strong recommendation for TNF inhibitors (infliximab, adalimumab, certolizumab pegol) to induce remission in patients who have not responded to conventional therapy, with moderate-quality evidence 1
• The AGA recommends infliximab, adalimumab, or ustekinumab over certolizumab pegol for induction in biologic-naïve patients 1

Safety Monitoring

• Screen all patients for tuberculosis (active and latent infection) prior to initiating infliximab and periodically during therapy 2
• Patients with active infection should not receive infliximab until adequately treated 3
• Pretreatment with diphenhydramine is recommended in patients with a history of infusion reactions or those at risk for delayed hypersensitivity reactions 3
• Approximately 20% of patients experience infusion reactions (flu-like symptoms, headache, dyspnea, hypotension, fever, chills, rash) compared to 10% with placebo 2

Common Pitfalls to Avoid

• Do not use single-dose or episodic infliximab therapy: The three-dose induction regimen (0,2,6 weeks) is essential for optimal outcomes and should not be abbreviated 3, 6
• Do not delay combination therapy: Starting thiopurines concurrently with infliximab is more effective than adding them later, as this prevents antibody formation from the outset 1
• Do not continue beyond week 14 in non-responders: Patients who fail to respond by this timepoint are unlikely to benefit from continued infliximab and should be switched to an alternative mechanism of action 2
• Do not use infliximab as monotherapy in biologic-naïve patients without considering combination therapy: The evidence strongly favors combination therapy for superior remission and mucosal healing rates 4