Efficacy, drug sustainability, and safety of ustekinumab treatment in Crohn's disease patients over three years.

Long-term data on ustekinumab in real-life Crohn's disease patients are still missing, though randomized controlled trials demonstrated it as a favorable therapeutic option. We aimed to evaluate ustekinumab's clinical efficacy, drug sustainability, and safety in a prospective, nationwide, multicenter Crohn's disease patient cohort with a three-year follow-up. Crohn's disease patients on ustekinumab treatment were consecutively enrolled from 9 Hungarian Inflammatory Bowel Disease centers between January 2019 and May 2020. Patient and disease characteristics, treatment history, clinical disease activity (Harvey Bradshaw Index (HBI)), biomarkers, and endoscopic activity (Simple Endoscopic Score for Crohn's Disease (SES-CD)) were collected for three-years' time. A total of 148 patients were included with an overall 48.9% of complex behavior of the Crohn's disease and 97.2% of previous anti-TNF exposure. The pre-induction remission rates were 12.2% (HBI), and 5.1% (SES-CD). Clinical remission rates (HBI) were 52.2%, 55.6%, and 50.9%, whereas criteria of an endoscopic remission were fulfilled in 14.3%, 27.5%, and 35.3% of the subjects at the end of the first, second, and third year, respectively. Dose intensification was high with 84.0% of the patients on an 8-weekly and 29.9% on a 4-weekly regimen at the end of year 3. Drug sustainability was 76.9% during the follow-up period with no serious adverse events observed. Ustekinumab in the long-term is an effective, sustainable, and safe therapeutic option for Crohn's disease patients with severe disease phenotype and high previous anti-TNF biological failure, requiring frequent dose intensifications.

Clinical efficacy, drug sustainability and serum drug levels in Crohn's disease patients treated with ustekinumab - A prospective, multicenter cohort from Hungary.

INTRODUCTION: Although efficacy of ustekinumab (UST) has been demonstrated through randomized trials, data from real-life prospective cohorts are still limited. Our aim was to evaluate clinical efficacy, drug sustainability, dose intensification and results from therapeutic drug monitoring in UST treated patients with Crohn's disease (CD) using a prospective, nationwide, multicenter cohort. METHODS: Patients from 10 Inflammatory Bowel Disease centers were enrolled between 2019 January and 2020 May. Patient demographics, disease phenotype, treatment history, clinical disease activity (Crohn's Disease Activity Index(CDAI), Harvey Bradshaw Index(HBI)), biomarkers, and serum drug levels were obtained. Evaluations were performed at week8 (post-induction), w16-20, w32-36, and w52-56 follow-up visits. RESULTS: A total of 142 patients were included [57.4% female; complex disease behavior (B2/B3):48%, previous anti-TNF exposition:97%]. Clinical response and remission rates after induction(w8) were 78.1% and 57.7% using CDAI, and 82.5% and 51.8% based on HBI scores. The one-year clinical remission rate was 58%/57.3%(CDAI/HBI). Composite clinical and biomarker remission (CDAI<150 and C-reactive protein<10 mg/L) rates were 35.4%; 33.3%; 38.6% and 36.6% at w8/w16-20/w32-36 and w52-56. Drug sustainability was 81.9%(standard deviation(SD): 3.4) at 1 year(1y). Probability of dose intensification was high and introduced early, 42.2%(SD:4.2) at ~w32 and 51.9%(SD:4.4%) at 1y. CONCLUSION: Ustekinumab showed favorable drug sustainability and clinical efficacy in a patient population with severe disease phenotype and previous anti-tumor necrosis factor (anti-TNF) failure, however frequent dose intensification was required.

Identification of the first VIM metallo-beta-lactamase-producing multiresistant Aeromonas hydrophila strain.

A VIM metallo-beta-lactamase-producing Aeromonas hydrophila strain carrying an integron-borne bla(VIM-4) gene was isolated from a cirrhotic patient's fecal sample in a Budapest hospital. The variable region of this integron is identical with that of a previously characterized integron from Pseudomonas aeruginosa clinical isolates in Pécs in southern Hungary.

Severity of gastroesophageal reflux disease influences daytime somnolence: a clinical study of 134 patients underwent upper panendoscopy.

AIM: To asses the relationship between severity of gastroesophageal refluxe disease and Epworth sleepiness scale as an indicator of daytime somnolence. METHODS: One hundred and thirty-four patients underwent an upper panendoscopy as indicated by the typical reflux symptoms and were also investigated with regard to somnolence. Sleepiness was evaluated by Epworth Sleepiness Scale, which was compared to the severity of endoscopic findings (Savary-Miller/modified by Siewert). Patients with psychiatric disorders or being on sedato-hypnotics as well as shift workers were excluded from the study. The relationship between the severity of the reflux disease and daytime somnolence was analyzed with the help of multivariate regression analysis. RESULTS: A positive tendency was found between the severity of the reflux disease and the corresponding Epworth Sleepiness Scale. In the case of the more severe type - Savary-Miller III - at least a mild hypersomnia was found. For this group daytime somnolence was significantly higher than in the case of the non-erosive type of Gastroesophageal Reflux Disease representing the mildest stage of reflux disease. CONCLUSION: The severity of Gastroesophageal Reflux Disease influences daytime somnolence.