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INTRODUCTION: This study wasdesigned to evaluate the safety of fontolizumab, a humanised anti-interferongamma antibody, in patients with moderate to severe Crohn's disease (CD).PATIENTS AND METHODS: Forty five patients with a CD activity index (CDAI) of250-450 were randomised in a double blind, placebo controlled, dose escalatingfashion to receive single doses of fontolizumab (0.1, 1.0, and 4.0 mg/kg) orplacebo. By day 29, patients with clinical response were re-randomised toreceive three additional doses of one half their initial fontolizumab dose orplacebo at four weekly intervals. Primary objectives were safety andtolerability. Secondary outcomes included assessments of immunogenicity,clinical activity, and potential pharmacodynamic surrogates. RESULTS: Treatmentwas generally well tolerated. There were slightly more reports of chills,flu-like syndrome, asthenia, nausea, and vomiting in the 1.0 mg and 4.0 mg/kgfontolizumab cohorts. Two serious adverse events rated as worsening of CDoccurred under fontolizumab. Antibodies to fontolizumab were confirmed in onepatient. No differences in clinical activity parameters were noted between anyof the active treatment groups and placebo, with the placebo group having a particularlyfavourable outcome (60% response and 40% remission). By day 29, a more enhanced decreasein median Crohn's disease endoscopic index of severity (p = 0.02) and serum Creactive protein (p<0.001) was observed in the 4.0 mg/kg (n = 14)fontolizumab cohort compared with placebo (n = 10). Pharmacodynamic effectswere observed by immunohistochemistry. CONCLUSIONS: Fontolizumab was welltolerated with minimal immunogenicity at doses of up to 4.0 mg/kg in patientswith CD. A biological activity of fontolizumab is suggested. Leggil'articolo
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