Fontolizumab, a humanised anti-interferon gamma antibody, demonstrates safety and clinical activity in patients with moderate to severe Crohn's disease.

Interferon gamma is a potent proinflammatory cytokine implicated in the inflammation of Crohn's disease (CD). We evaluated the safety and efficacy of fontolizumab, a humanised anti-interferon gamma antibody, in patients with moderate to severe CD. A total of 133 patients with Crohn's disease activity index (CDAI) scores between 250 and 450, inclusive, were randomised to receive placebo or fontolizumab 4 or 10 mg/kg. Forty two patients received one dose and 91 patients received two doses on days 0 and 28. Investigators and patients were unaware of assignment. Study end points were safety, clinical response (decrease in CDAI of 100 points or more), and remission (CDAI < or =150). There was no statistically significant difference in the primary end point of the study (clinical response) between the fontolizumab and placebo groups after a single dose at day 28. However, patients receiving two doses of fontolizumab demonstrated doubling in response rate at day 56 compared with placebo: 32% (9/28) versus 69% (22/32, p = 0.02) and 67% (21/31, p = 0.03) for the placebo, and 4 and 10 mg/kg fontolizumab groups, respectively. Stratification according to elevated baseline C reactive protein levels resulted in a decreased placebo response and pronounced differences in clinical benefit. Two grade 3 adverse events were reported and were considered to be related to CD. One death (during sleep) and one serious adverse event (an elective hospitalisation) occurred, both considered unrelated. Treating active CD with fontolizumab was well tolerated and resulted in increased rates of clinical response and remission compared with placebo.