Systematic review with meta-analysis: placebo rates in induction and maintenance trials of Crohn's disease.

BACKGROUND: Minimising placebo response is essential for drug development. AIM: To conduct a meta-analysis to determine placebo response and remission rates in trials and identify the factors affecting these rates. METHODS: MEDLINE, EMBASE and CENTRAL were searched from inception to April 2014 for placebo-controlled trials of pharmacological interventions for Crohn's disease. Placebo response and remission rates for induction and maintenance trials were pooled by random-effects and mixed-effects meta-regression models to evaluate effects of study-level characteristics on these rates. RESULTS: In 100 studies containing 67 induction and 40 maintenance phases and 7638 participants, pooled placebo remission and response rates for induction trials were 18% [95% confidence interval (CI) 16-21%] and 28% (95% CI 24-32%), respectively. Corresponding values for maintenance trials were 32% (95% CI 25-39%) and 26% (95% CI 19-35%), respectively. For remission, trials enrolling patients with more severe disease activity, longer disease duration and more study centres were associated with lower placebo rates, whereas more study visits and longer study duration was associated with higher placebo rates. For response, findings were opposite such that trials enrolling patients with less severe disease activity and longer study duration were associated with lower placebo rates. Placebo rates varied by drug class and route of administration, with the highest placebo response rates observed for biologics. CONCLUSIONS: Placebo rates vary according to whether trials are designed for induction or maintenance and the factors influencing them differ for the endpoints of remission and response. These findings have important implications for clinical trial design in Crohn's disease.

The safety and efficacy of antitumour necrosis factor-alpha therapy for inflammatory bowel disease in patients post liver transplantation: a case series.

BACKGROUND: The role of antitumour necrosis factor-alpha (anti-TNF) therapy for inflammatory bowel disease (IBD) among liver transplant recipients is largely unknown given the rarity of this population and the paucity of literature on the subject. AIM: To investigate the safety and efficacy of anti-TNF therapy for refractory IBD in the post liver transplant population. METHODS: The liver transplant database at London Health Sciences Centre was searched to identify adult patients with IBD treated with anti-TNF therapy post transplantation. RESULTS: Six patients (five men, one woman) were identified, aged 28-65. All patients had cadaveric orthotopic liver transplants. Four patients required transplantation due to primary sclerosing cholangitis, one due to autoimmune hepatitis, and one due to biliary atresia. Five patients suffered from Crohn's disease and the remaining patient from indeterminate colitis. All patients were treated with infliximab 5 mg/kg every 8 weeks after undergoing induction at weeks 0, 2 and 6, with the exception of one patient. The duration of infliximab therapy ranged from 8 weeks to 4 years. Four patients treated with infliximab experienced sustained improvement of their IBD symptoms post transplantation, as documented by Harvey-Bradshaw Index scores demonstrating clinical remission. Of the remaining two patients, neither had sustained improvement of their IBD with infliximab or subsequent adalimumab. One patient was diagnosed with systemic lupus erythematosus and another with colorectal adenocarcinoma following anti-TNF therapy. Otherwise, no side effects were attributed to anti-TNF therapy. CONCLUSIONS: Based on this case series, anti-TNF therapy appears to be safe and effective for treating refractory IBD in patients post liver transplantation. These patients respond to anti-TNF therapy similar to those who have not been previously transplanted.