摘要
Introduction:Interferon γ 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 γ antibody,in patients with moderate to severe CD.Methods: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 ≤ 150) .Results: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 10mg/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.Conc-lusion:Treating active CD with fontolizumab was well tolerated and resulted in increased rates of clinical response and remission compared with placebo.
Introduction:Interferon γ 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 γ antibody,in patients with moderate to severe CD.Methods: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 ≤ 150) .Results: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 10mg/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.Conc-lusion:Treating active CD with fontolizumab was well tolerated and resulted in increased rates of clinical response and remission compared with placebo.
