New Safety (new + safety)

Distribution by Scientific Domains

Selected Abstracts

Treatment of ulcerative colitis with adalimumab or infliximab: long-term follow-up of a single-centre cohort

N. Gies
Aliment Pharmacol Ther 2010; 32: 522,528 Summary Background, Randomized, controlled trials have demonstrated that anti-TNF agents are efficacious in inducing remission in cases of Crohn's disease and ulcerative colitis. However, response rates for anti-TNF agents in ,real life' clinical practice are less well-defined. Aims, To examine the response rates and long-term outcomes of infliximab and adalimumab treatment for out-patients with ulcerative colitis and to study the variables associated with response rates. Methods, In a prospective study, a single-centre out-patient cohort was treated and followed up according to a structured protocol of clinical care. Response to treatment was assessed using a physician's global assessment that focused on normalization of bowel frequency, absence of blood with defecation and tapering of corticosteroids to zero. Results, Fifty-three ulcerative colitis patients were included in the study. Responses to induction therapy were 96.4% (27/28) for infliximab and 80% (20/25) for adalimumab (P = 0.0889). Responses to maintenance therapy were similar: infliximab 77.8% (14/18) and adalimumab 70.0% (14/20) (P = 0.7190). Multivariate analyses of the induction and maintenance responses did not reveal confounding elements. No new safety signals were identified. Conclusions, This long-term follow-up of a single-centre cohort of ulcerative colitis patients demonstrates that ,real-life' out-patient treatment with infliximab and adalimumab is effective in induction and maintenance of response. [source]

Adalimumab sustains clinical remission and overall clinical benefit after 2 years of therapy for Crohn's disease

Aliment Pharmacol Ther,31, 1296,1309 Summary Background, In the randomized, double-blind, placebo-controlled CHARM trial, adalimumab was more effective than placebo in maintaining clinical remission for patients with moderate-to-severe Crohn's disease (CD) through 56 weeks. Aim, To substantiate the long-term safety and clinical benefits of adalimumab through 2 years of therapy in CHARM and its open-label extension (ADHERE). Methods, Patients entering ADHERE on blinded therapy received adalimumab 40 mg every other week (eow). Patients who had already moved to open-label adalimumab eow or weekly in CHARM continued their regimens. Data were analysed by originally randomized treatment group at CHARM baseline (adalimumab 40 mg eow, adalimumab 40 mg weekly, or placebo), regardless of whether patients entered ADHERE or received open-label adalimumab (eow or weekly). Results, After up to 2 years of therapy, 37.6%, 41.9% and 49.8% of patients originally randomized to placebo, adalimumab eow and adalimumab weekly, respectively, were in clinical remission. All groups experienced sustained improvements on the Inflammatory Bowel Disease Questionnaire. Decreasing hazard rates for both all-cause and CD-related hospitalizations were observed over time. Over a 2-year period, the rates of serious adverse events and malignancies (33.3 and 1.1 events/100-patient-years respectively) were similar to those observed during the overall adalimumab CD clinical development programme. Conclusions, Adalimumab demonstrated sustained maintenance of clinical remission, improvements in quality of life and reductions in hospitalization during long-term treatment for CD, with no new safety concerns identified. [source]

Infliximab safety profile and long-term applicability in inflammatory bowel disease: 9-year experience in clinical practice

Aliment Pharmacol Ther,31, 553,560 Summary Background, Most available data on infliximab therapy come from large, short-term, pivotal RCTs and concerns about long-term safety profile still remain. Aim, To evaluate the long-term safety profile of infliximab in inflammatory bowel disease (IBD) in a clinical practice setting. Methods, Since 1999, all IBD patients treated with infliximab were registered and clinical outcomes prospectively recorded up to March 2008, loss of follow-up or patient's death. Infliximab regimens and preventive measures were in accordance with the prevalent guidelines or with the manufacturer's recommendations. Results, One hundred fifty-two patients were included (121 Crohn's disease, 24 ulcerative colitis, 7 indeterminate colitis), with a median of 5 infliximab infusions (IQR 3,8) and 87% of patients received at least three infusions. Seventy-nine per cent of them received concomitant immunomodulators and 70% were pre-medicated with hydrocortisone from the first infusion. After a median follow-up of 142 weeks, 13% presented infusion reactions, 13% viral or bacterial infections and two patients developed neoplasia. The mortality rate was 2.6% (four patients). Conclusions, Infliximab therapy is safe when the recommended preventive measures are implemented, with a rate of serious adverse events less than 10%. No new safety signals were found. [source]

A quantitative approach to benefit-risk assessment of medicines , part 1: the development of a new model using multi-criteria decision analysis,

Filip Mussen PhD
Abstract Purpose One of the most important uses of benefit-risk assessment pertains to approval of new medicines by regulatory authorities and the subsequent review of these products during their life-cycle when new safety and/or efficacy data becomes available. At present, there exist no validated, well-accepted models for benefit-risk assessment that have the appropriate degree of sophistication, and as a consequence no models are widely used by regulatory authorities or industry. The aim of the study was therefore to develop a new model for benefit-risk assessment of medicines using multi-criteria decision analysis (MCDA). Methods The MCDA methodology was used for a systematic approach to assess the benefit risk ratio of medicines. The reasons for adopting this approach were (1) taking multiple benefit and risk criteria into account, (2) making a judgement on the evidence and potential uncertainty because of the incompleteness of evidence, and (3) making trade-offs of the benefits against risks. Results It was demonstrated through a seven-step approach how MCDA is used to construct the model. Ten benefit and ten risk criteria were identified to form a value tree. Then fixed scales were established for all criteria and options on the criteria were scored. Weights were assigned for each criteria using swing-weighting. Finally sensitivity analysis was carried. Conclusions This novel approach based on MCDA has the potential for being applied as a new tool for judging and deciding on the benefits and risks, thereby helping regulators and industry in the development and approval of new medicines and their adequate use. Copyright 2007 John Wiley & Sons, Ltd. [source]