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“Background In a subset of patients, anti tumour necrosis factor (TNF) therapeutic antibodies are immunogenic, resulting in the formation of antidrug antibodies (ADAs). Neutralising ADAs compete with TNF for its binding site and reduces the effective serum concentration, causing clinical non-response. It is however unknown to which extent ADAs are neutralising. Objectives To study which proportion of antibodies to human(ised) anti-TNF (adalimumab, golimumab, certolizumab) as well as chimeric anti-TNF (infliximab) is neutralising. Methods Neutralising capacity of ADAs was assessed using a TNF competition assay in ADA-positive

sera of patients treated with adalimumab (n=21), golimumab (n=4), certolizumab (n=9) or infliximab (n=34) sent in to our diagnostic department. Results In 34 sera with ADAs to adalimumab, golimumab or certolizumab, EGFR inhibitor bigger than 97% of the antibodies were neutralising. In 34 sera with ADAs to infliximab bigger than 90% of the antibodies were neutralising. Further characterisation of the broader antibody response BEZ235 to infliximab revealed that non-neutralising antibodies to infliximab do not target murine domains, but may bind infliximab-unique domains not involved in TNF binding (located outside the paratope). Conclusions Our study shows that ADAs to human (ised)

as well as chimeric anti-TNF therapeutic antibodies are largely neutralising. This highly restricted ADA response suggests an immunodominant Nepicastat mw role for the paratope of anti-TNF therapeutics.”
“Background and aims: Previous clinical trials suggest that adding non-selective beta-blockers improves the efficacy of endoscopic band ligation (EBL) in the prevention of recurrent bleeding, but no study has evaluated whether EBL improves the efficacy of beta-blockers + isosorbide-5-mononitrate. The present study was aimed at evaluating this issue in a multicentre randomised controlled trial (RCT) and to correlate changes in hepatic venous pressure gradient (HVPG) during treatment with clinical outcomes\n\nMethods: 158 patients with cirrhosis,

admitted because of variceal bleeding, were randomised to receive nadolol+isosorbide-5-mononitrate alone (Drug: n = 78) or combined with EBL (Drug+EBL; n = 80). HVPG measurements were performed at randomisation and after 4-6 weeks on medical therapy.\n\nResults: Median follow-up was 15 months. One-year probability of recurrent bleeding was similar in both groups (33% vs 26%: p = 0.3). There were no significant differences in survival or need of rescue shunts. Overall adverse events or those requiring hospital admission were significantly more frequent in the Drug+EBL group. Recurrent bleeding was significantly more frequent in HVPG non-responders than in responders (HVPG reduction >= 20% or <= 12 mm Hg). Among non-responders recurrent bleeding was similar in patients treated with Drugs or Drugs+EBL.