Changes in plasma gonadotropin after ovariectomy and estradiol supplementation at different stages at the end of the reproductive cycle in the rainbow trout (Salmo gairdneri R.)

International audienceTo determine the effect of gonadal feedback on plasma GTH level, female rainbow trout were ovariectomized at three stages at the end of the reproductive cycle : at the end of vitellogenesis, during germinal vesicle migration and during the post-ovulatory period. A group of controls and one of castrates in each experiment were given an injection of physiological salt solution, and a third group of castrates was supplemented with estradiol- 17β (E2) twice a week (200 μg/kg) from the day of surgery. The blood was sampled twice a week, and the GTH measured by RIA. At the end of vitellogenesis, castration induced a significant rise in the gonadotropic hormone level (P < 0.001 from post-surgical day 5), and that response, unimpeded by E2 was homogeneous in all the fish. During germinal vesicle migration, the response to castration and to supplementary E2 varied with the individual. Ovariectomy induced a significant increase in GTH (P < 0.005 from day 3), but that increase was immediate in 5 females and delayed in the other 4 ; E2 prevented GTH rise in only 6 females. At the post-ovulatory period we found no significant difference between the control fish and the castrates and E2, at least temporarily, prevented the post-ovulatory rise in GTH which is usually found in trout

Effectiveness and Safety of Vedolizumab Induction Therapy for Patients with Inflammatory Bowel Disease

International audienceBackground & aims - Phase 3 trials have shown the efficacy of vedolizumab, which binds to integrin α4β7, in patients with Crohn's disease (CD) or ulcerative colitis (UC). We investigated the effectiveness and safety of vedolizumab in patients who failed anti-tumor necrosis factor therapy. Methods - From June through December 2014, there were 173 patients with CD and 121 patients with UC who were included in a multicenter nominative compassionate early access program granted by French regulatory agencies. This program provided patients with access to vedolizumab before it was authorized for marketing. Vedolizumab (300 mg) was administered intravenously at weeks 0, 2, and 6, and then every 8 weeks. Disease activity was assessed using the Harvey-Bradshaw Index for CD and the partial Mayo Clinic score for UC. We report results obtained after the 14-week induction phase. Results - Among the 294 patients treated with vedolizumab (mean age, 39.5 ± 14.0 y; mean disease duration, 10.8 ± 7.6 y; concomitant steroids, 44% of cases), 276 completed the induction period, however, 18 discontinued vedolizumab because of a lack of response (n = 14), infusion-related reaction (n = 2), or infections (n = 2). At week 14, 31% of patients with CD were in steroid-free clinical remission and 51% had a response; among patients with UC, 36% were in steroid-free clinical remission and 50% had a response. No deaths were reported. Severe adverse events occurred in 24 patients (8.2%), including 15 (5.1%) that led to vedolizumab discontinuation (1 case of pulmonary tuberculosis and 1 rectal adenocarcinoma). Conclusions - In a cohort of patients with CD or UC who failed previous anti-tumor necrosis factor therapy, approximately one third of patients achieved steroid-free clinical remission after 14 weeks of induction therapy with vedolizumab. This agent had an acceptable safety profile in these patients

A clinical decision support tool may help to optimise vedolizumab therapy in Crohn's disease

International audienceBackground A clinical decision support tool (CDST) has been validated for predicting treatment effectiveness of vedolizumab (VDZ) in Crohn's disease. Aim To assess the utility of this CDST for predicting exposure-efficacy and disease outcomes. Methods Using data from three independent datasets (GEMINI, GETAID and VICTORY), we assessed clinical remission rates and measured VDZ exposure, rapidity of onset of action, response to dose optimisation and progression to surgery by CDST-defined response groups (low, intermediate and high). Results A linear relationship existed between CDST-defined groups, measured VDZ exposure, rapidity of onset of action and efficacy in GEMINI through week 52 (P < 0.001 at all time points across three CDST-defined groups). In GETAID, CDST predicted differences in clinical remission at week 14 (AUC = 0.68) and rapidity of onset of action (P = 0.04) between probability groups. The high-probability patients did not benefit from shortening of infusion intervals, and differences in onset of action between the high-intermediate and low-probability groups within GETAID were no longer significant when including low-probability patients who received a week 10 infusion. CDST predicted a twofold increase in surgery risk over 12 months of VDZ therapy among low- to intermediate-probability vs high-probability patients (adjusted HR 2.06, 95% CI 1.33-3.21). Conclusions We further extended the clinical utility of a previously validated VDZ CDST, which accurately predicts at baseline exposure-efficacy relationships and rapidity of onset of action and could be used to help identify patients who would most benefit from interval shortening and those most likely to require surgery while on active therapy