The prior diagnosis of fatal astrocytoma in a 60-year-old man with Crohn’s disease treated with natalizumab, a monoclonal antibody against α4 integrins, was reclassified as JC virus-related progressive multifocal le...The prior diagnosis of fatal astrocytoma in a 60-year-old man with Crohn’s disease treated with natalizumab, a monoclonal antibody against α4 integrins, was reclassified as JC virus-related progressive multifocal leukoencephalopathy (PML). Analysis of frozen serum samples showed that JC virus DNA had appeared in the serum three months after the initiation of open-label natalizumab monotherapy and two months before the appearance of symptomatic PML. There was staining of the brain lesion for polyomavirus. This case report, along with two others, suggests that anti-α4-integrin therapy can result in JC virus-induced PML.展开更多
Background: Healing of mucosal lesions appears to offer significant benefit and is an important end point in clinical trials of treatment for Crohn’s disease. The only validated endoscopic activity score at present i...Background: Healing of mucosal lesions appears to offer significant benefit and is an important end point in clinical trials of treatment for Crohn’s disease. The only validated endoscopic activity score at present is the Crohn’s Disease Endoscopic Index of Severity, which is complicated and time consuming and, hence, is unsuitable for routine use. The aim of this study was to develop and to prospectively validate a simpler endoscopic score of disease activity, the Simple Endoscopic Score for Crohn’s Disease. Methods: Selected endoscopic parameters (ulcer size, ulcerated and affected surfaces, stenosis) were scored from 0 to 3. Reproducibility for scoring of these parameters was evaluated through 71 examinations in which the endoscopist was paired with an observer. The simplest score (Simple Endoscopic Score for Crohn’s Disease) that was highly correlated with both the Crohn’s Disease Endoscopic Index of Severity and Crohn’s Disease Activity Index was derived for 70 patients and then was prospectively validated in 121 different patients with Crohn’s disease. Results: The interobserver agreement for all selected endoscopic variables was excellent (kappa coefficient 0.791-1.000). Based on multiple linear regression, the Simple Endoscopic Score for Crohn’s Disease resulted in the sum of the scores for ulcer size, ulcerated surface, affected surface, and luminal narrowing. In the validation phase of the study, a strong correlation was demonstrated for the Simple Endoscopic Score for Crohn’s Disease with Crohn’s Disease Endoscopic Index of Severity (r = 0.920). In addition, the Simple Endoscopic Score for Crohn’s Disease was correlated to clinical parameters and serum C-reactive protein level. Conclusions: Simple Endoscopic Score for Crohn’s Disease is a simple, reproducible, and easy-to-use endoscopic scoring system for Crohn’s disease.展开更多
Introduction:This study was designed to evaluate the safety of fontolizumab,a humanised anti-interferon γ antibody,in patients with moderate to severe Crohn’s disease(CD) .Patients and methods:Forty five patients wi...Introduction:This study was designed to evaluate the safety of fontolizumab,a humanised anti-interferon γ antibody,in patients with moderate to severe Crohn’s disease(CD) .Patients and methods:Forty five patients with a CD activity index(CDAI) of 250-450 were randomised in a double blind,placebo controlled,dose escalating fashion to receive single doses of fontolizumab(0.1,1.0,and 4.0 mg/kg) or placebo.By day 29,patients with clinical response were re-randomised to receive three additional doses of one half their initial fontolizumab dose or placebo at four weekly intervals.Primary objectives were safety and tolerability.Secondary outcomes included assessments of immunogenicity,clinical activity,and potential pharmacodynamic surrogates.Results:Treatment was 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/kg fontolizumab cohorts.Two serious adverse events rated as worsening of CD occurred under fontolizumab.Antibodies to fontolizumab were confirmed in one patient.No differences in clinical activity parameters were noted between any of the active treatment groups and placebo,with the placebo group having a particularly favourable outcome(60% response and 40% remission) .By day 29,a more enhanced decrease in median Crohn’s disease endoscopic index of severity(p = 0.02) and serum C reactive protein(p< 0.001) was observed in the 4.0 mg/kg(n = 14) fontolizumab cohort compared with placebo(n = 10) .Pharmacodynamic effects were observed by immunohistochemistry.Conclusions:Fontolizumab was well tolerated with minimal immunogenicity at doses of up to 4.0 mg/kg in patients with CD.A biological activity of fontolizumab is suggested.展开更多
文摘The prior diagnosis of fatal astrocytoma in a 60-year-old man with Crohn’s disease treated with natalizumab, a monoclonal antibody against α4 integrins, was reclassified as JC virus-related progressive multifocal leukoencephalopathy (PML). Analysis of frozen serum samples showed that JC virus DNA had appeared in the serum three months after the initiation of open-label natalizumab monotherapy and two months before the appearance of symptomatic PML. There was staining of the brain lesion for polyomavirus. This case report, along with two others, suggests that anti-α4-integrin therapy can result in JC virus-induced PML.
文摘Background: Healing of mucosal lesions appears to offer significant benefit and is an important end point in clinical trials of treatment for Crohn’s disease. The only validated endoscopic activity score at present is the Crohn’s Disease Endoscopic Index of Severity, which is complicated and time consuming and, hence, is unsuitable for routine use. The aim of this study was to develop and to prospectively validate a simpler endoscopic score of disease activity, the Simple Endoscopic Score for Crohn’s Disease. Methods: Selected endoscopic parameters (ulcer size, ulcerated and affected surfaces, stenosis) were scored from 0 to 3. Reproducibility for scoring of these parameters was evaluated through 71 examinations in which the endoscopist was paired with an observer. The simplest score (Simple Endoscopic Score for Crohn’s Disease) that was highly correlated with both the Crohn’s Disease Endoscopic Index of Severity and Crohn’s Disease Activity Index was derived for 70 patients and then was prospectively validated in 121 different patients with Crohn’s disease. Results: The interobserver agreement for all selected endoscopic variables was excellent (kappa coefficient 0.791-1.000). Based on multiple linear regression, the Simple Endoscopic Score for Crohn’s Disease resulted in the sum of the scores for ulcer size, ulcerated surface, affected surface, and luminal narrowing. In the validation phase of the study, a strong correlation was demonstrated for the Simple Endoscopic Score for Crohn’s Disease with Crohn’s Disease Endoscopic Index of Severity (r = 0.920). In addition, the Simple Endoscopic Score for Crohn’s Disease was correlated to clinical parameters and serum C-reactive protein level. Conclusions: Simple Endoscopic Score for Crohn’s Disease is a simple, reproducible, and easy-to-use endoscopic scoring system for Crohn’s disease.
文摘Introduction:This study was designed to evaluate the safety of fontolizumab,a humanised anti-interferon γ antibody,in patients with moderate to severe Crohn’s disease(CD) .Patients and methods:Forty five patients with a CD activity index(CDAI) of 250-450 were randomised in a double blind,placebo controlled,dose escalating fashion to receive single doses of fontolizumab(0.1,1.0,and 4.0 mg/kg) or placebo.By day 29,patients with clinical response were re-randomised to receive three additional doses of one half their initial fontolizumab dose or placebo at four weekly intervals.Primary objectives were safety and tolerability.Secondary outcomes included assessments of immunogenicity,clinical activity,and potential pharmacodynamic surrogates.Results:Treatment was 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/kg fontolizumab cohorts.Two serious adverse events rated as worsening of CD occurred under fontolizumab.Antibodies to fontolizumab were confirmed in one patient.No differences in clinical activity parameters were noted between any of the active treatment groups and placebo,with the placebo group having a particularly favourable outcome(60% response and 40% remission) .By day 29,a more enhanced decrease in median Crohn’s disease endoscopic index of severity(p = 0.02) and serum C reactive protein(p< 0.001) was observed in the 4.0 mg/kg(n = 14) fontolizumab cohort compared with placebo(n = 10) .Pharmacodynamic effects were observed by immunohistochemistry.Conclusions:Fontolizumab was well tolerated with minimal immunogenicity at doses of up to 4.0 mg/kg in patients with CD.A biological activity of fontolizumab is suggested.
