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"Infliximab, Azathioprine, or Combination for Crohn's Disease".The New England Journal of Medicine. 2010. 362(15):1383-1395.PubMed•Full text•PDF

1Clinical Question
2Bottom Line
3Major Points
4Guidelines
5Design
6Population
6.1Inclusion Criteria
6.2Exclusion Criteria
6.3Baseline Characteristics
7Interventions
8Outcomes
8.1Primary Outcome
8.2Secondary Outcomes
9Funding
10Further Reading

Clinical Question

In adult patients with moderate-to-severe Crohn's disease naïve to immunosuppressives and biologics, is combination therapy with infliximab and azathioprine more effective than either agent alone for inducing corticosteroid-free clinical remission?

Bottom Line

For adults with moderate-to-severe Crohn's disease naïve to immunosuppressive or biologic therapy, combination therapy with infliximab and azathioprine was more effective in inducing corticosteroid-free clinical remission than monotherapy with either agent.

Major Points

Crohn's disease is a chronic inflammatory disorder where progression may lead to complications. Corticosteroids, mesalamine, budesonide, azathioprine, and anti-tumor necrosis factor (TNF) such as infliximab are currently used to manage symptoms. Previous studies indicated individual benefits of infliximab and azathioprine, but their combined efficacy had not been evaluated in a naïve patient population.

Guidelines

As of 2010, the American College of Gastroenterology recommended that infliximab could be considered for induction of remission in moderate-to-severe Crohn's disease that does not respond to conventional treatments, and combination therapy with azathioprine may be used in some patients.

Design

Multicenter, double-blind, parallel-group, randomized, placebo-controlled trial

N=508 adult patients with moderate-to-severe Crohn's disease

Interventions:

- Infliximab (5 mg/kg IV at weeks 0, 2, 6, then every 8 weeks) + placebo capsules
- Azathioprine (2.5 mg/kg orally daily) + placebo infusions
- Combination therapy with infliximab and azathioprine

Setting: 92 centers from March 2005 through November 2008
Enrollment: 2005-2008
Mean follow-up: 30 weeks with optional 20-week blinded extension
Analysis: Intention-to-treat
Primary outcome: Corticosteroid-free clinical remission at week 26

Population

Inclusion Criteria:
- At least 21 years of age
- Diagnosed with Crohn's disease for at least 6 weeks
- CDAI score of 220 to 450
- Corticosteroid-dependent or under consideration for corticosteroids

Exclusion Criteria:
- Previous treatment with azathioprine, 6-mercaptopurine, methotrexate, or any anti-TNF biologic agent
- Contraindications such as tuberculosis, hep B or C, short bowel syndrome, recent abdominal surgery, severe cardiac failure

Baseline Characteristics
Demographics and disease characteristics were similar across all groups.

Interventions

Patients were randomized to one of three groups and received study medication through week 30 with the option to continue in a blinded study extension through week 50.

Outcomes

Primary Outcome:
- Corticosteroid-free clinical remission at week 26: 56.8% (combination), 44.4% (infliximab), 30.0% (azathioprine)

Secondary Outcomes:
- Mucosal healing at week 26: 43.9% (combination), 30.1% (infliximab), 16.5% (azathioprine)
- Higher corticosteroid-free clinical remission at week 50 for the combination therapy group compared to azathioprine alone
- Similar rates of adverse events among all treatment groups

Funding

Supported by Centocor Ortho Biotech and Schering-Plough.