"Infliximab, Azathioprine, or Combination for Crohn's Disease".The New England Journal of Medicine. 2010. 362(15):1383-1395.
Links to original sources: Wiki Journal Post Full Journal Article
Contents 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
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?
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.
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.
This study (SONIC) found that combination therapy with infliximab and azathioprine was more effective at achieving corticosteroid-free clinical remission at week 26 compared to monotherapy with either drug. Mucosal healing at 26 weeks was also highest in the combination group compared to either monotherapy. Outcomes at week 50 supported the superiority of combination therapy, with higher rates of corticosteroid-free clinical remission versus azathioprine alone. Rates of adverse events were similar among treatment groups.
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.
Multicenter, double-blind, parallel-group, randomized, placebo-controlled trial
N=508 adult patients with moderate-to-severe Crohn's disease
- 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
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.
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.
Primary Outcome: - Corticosteroid-free clinical remission at week 26: 56.8% (combination), 44.4% (infliximab), 30.0% (azathioprine)
- 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
Supported by Centocor Ortho Biotech and Schering-Plough.
For more reading, the full study "Infliximab, Azathioprine, or Combination for Crohn's Disease" can be accessed at the New England Journal of Medicine, with supplementary material available at NEJM.org.