Infliximab induction and maintenance therapy for ulcerative colitis: the ACT 2 trial

Background: The efficacy of infliximab (IFX) for the treatment of ulcerative colitis (UC) was previously unknown. Two Phase 3 trials, ACT I and ACT 2, evaluated the safety and efficacy of IFX for treatment of active UC. Results from ACT 2 are presented.

Methods: 364 patients with UC, refractory to at least one standard therapy including 5-ASA, corticosteroids, or immunosuppressants, were randomized to receive IFX 5 mg/kg, IFX 10mg/kg, or placebo at wks 0, 2, 6, 14 and 22. The primary endpoint was induction of clinical response, defined as a decrease in the Mayo score of ≥30% and ≥3 points, accompanied by a decrease in the rectal bleeding score of ≥1 or a rectal bleeding score of 0 or 1 at wk 8. Clinical remission, a secondary endpoint, was defined as a Mayo score ≤2, with no individual subscores >1, and mucosal healing was defined as an endoscopy subscore of 0 or 1.

Results: 64.5% of patients receiving IFX 5mg/kg and 69.2% receiving 10mg/kg were in clinical response at wk 8 vs. 29.3% who received placebo (p<0.001 for both). At wk 30, 47.1% of patients receiving IFX 5mg/kg and 60% receiving 10mg/kg were in clinical response vs. 26% of patients receiving placebo (p<0.001 for both). Clinical remission was achieved at wk 8 in 33.9% and 27.5% of IFX 5 and 10mg/kg patients, respectively, compared to 5.7% of placebo-treated patients (p<0.001 for both). Differences in remission rates persisted at wk 30 (25.6%, 5mg/kg; 35.8%, 10mg/kg; 10.6%, placebo; p=0.003 and p<0.001). Mucosal healing was achieved at wk 8 in 60.3% and 61.7% of patients receiving IFX 5mg/kg and 10 mg/kg, respectively, compared to 30.9% of placebo-treated patients (p<0.001 for both). Mucosal healing at wk 30 was achieved in 46.3% and 56.7% of patients receiving IFX 5 and 10 mg/kg, respectively, vs. 30.1% of placebo-treated patients (p=0.009 and p<0.001). The proportion of patients who were able to discontinue corticosteroids while in clinical remission at wk 30 was significantly greater in both IFX groups compared with the placebo group (18.3%, 5mg/kg; 27.3%, 10mg/kg; 3.3%, placebo; p<0.001 and p=0.010, respectively). IFX was generally well tolerated with a safety profile similar to that previously reported.

Conclusion: In patients with moderate-to-severe UC, IFX induces and maintains clinical response, clinical remission and mucosal healing, and permits the tapering of corticosteroids while maintaining remission.