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evident
Original paper
2010NEJMGastroenterology/Hepatology

SONIC

Infliximab, azathioprine, or combination therapy for Crohn's disease

RCTInflammatory bowel disease

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Overview

Combination infliximab plus azathioprine induced more steroid-free remission in Crohn disease.

Clinical takeaway

SONIC established the efficacy of early biologic-based therapy and combination therapy in biologic- and immunomodulator-naive Crohn disease.

Key result

Steroid-free remission at week 26 was highest with infliximab plus azathioprine.

Practice impact

Biologic therapy moved earlier for moderate-severe Crohn disease, with combination therapy considered in selected patients.

Evidence

Study design

Randomized double-blind trial.

Enrollment

508

Follow-up

Primary outcome at week 26.

Geography

Multinational

Clinical question

In Crohn disease naive to immunomodulators and biologics, is infliximab, azathioprine, or combination therapy most effective?

Population

  • Adults with moderate-to-severe Crohn disease naive to immunomodulators and biologic therapy.

Intervention

Infliximab plus azathioprine, or infliximab alone.

Comparator

Azathioprine alone and active treatment comparisons.

Primary outcome

Corticosteroid-free clinical remission at week 26.

Combination infliximab plus azathioprine produced the highest steroid-free remission rate.

Absolute remission rate / 56.8

Key results

  • Steroid-free remission at week 26: 56.8% combination vs 44.4% infliximab alone (p=0.02) vs 30.0% azathioprine alone (p<0.001 vs combination; p=0.006 for infliximab vs azathioprine).
  • Mucosal healing at week 26: 43.9% combination vs 30.1% infliximab (p=0.06) vs 16.5% azathioprine (p<0.001 vs combination; p=0.02 vs infliximab).
  • Serious infections: 3.9% combination, 4.9% infliximab, 5.6% azathioprine; similar in the trial, but immunosuppression risks remain important.

Harms

  • Combination immunosuppression can increase infection and malignancy concerns.
  • Thiopurine toxicity requires TPMT/NUDT15 and lab monitoring in modern practice.

Clinical Use

Practice impact

  • Shifted moderate-severe Crohn disease toward earlier biologic therapy and selected combination therapy.

Applicability

  • Biologic- and immunomodulator-naive patients with moderate-to-severe Crohn disease.

Limitations

  • Does not answer every modern biologic or small-molecule sequencing question.
  • Risk-benefit differs by age, EBV status, malignancy risk, and infection risk.

Common misinterpretations

  • Combination therapy is not mandatory for every Crohn patient; selection and monitoring matter.

Citation

Colombel JF, Sandborn WJ, Reinisch W, et al. Infliximab, azathioprine, or combination therapy for Crohn's disease. N Engl J Med. 2010;362(15):1383-1395. doi:10.1056/NEJMoa0904492

Patients with moderate-to-severe Crohn's disease who were treated with infliximab plus azathioprine or infliximab monotherapy were more likely to have a corticosteroid-free clinical remission than those receiving azathioprine monotherapy.