Background In 2018, the European Medicines Agency (EMA) replaced a fixed 50 mg every 4-week maintenance regimen of golimumab for ulcerative colitis (UC) patients weighing <80 kg with new, flexible dosing that allows reactive dose optimization to 100 mg if clinically needed. We analyzed the endoscopic remission rates and pharmacokinetics of this new dosing regimen in real-life settings. Methods We prospectively recruited 30 consecutive (17 with body weight <80 kg) patients with UC who received golimumab with the new EMA label. The primary endpoint was endoscopic remission (Mayo ≤1) assessed by centrally-read endoscopy at week 14 and year 1. Golimumab concentrations, measured at nine prespecified timepoints, were correlated with endoscopic remission and identified cut-offs. Results Endoscopic remission was achieved in 15/30 (50%) and 10/30 (33%) patients at week 14 and year 1, respectively. Reactive dose optimization to 100 mg maintenance was needed in 13/17 (76%) patients. Golimumab concentrations at week 6 predicted week 14 and year 1 endoscopic remission. Week 6 concentrations >10.7 µg/ml were a strong predictor for achievement and maintenance of endoscopic remission during the first year of treatment, while concentrations <5.1 µg/ml identified the opposite. Conclusion One-third of the patients reached and maintained endoscopic remission during the first year of golimumab treatment, but the need for dose optimization to 100 mg every 4 weeks of maintenance was high in patients weighing <80 kg. Golimumab concentrations <5.1 µg/ml at week 6 identified patients who are unlikely to reach and maintain endoscopic remission with the new, flexible EMA label.

Gastric outlet obstruction (GOO) is a clinical syndrome secondary to luminal obstruction at the level of the stomach and/or duodenum. GOO can be caused by either benign or malignant etiologies, often resulting in early satiety, nausea, vomiting and poor oral intake. GOO is associated with decreased quality of life and has been shown to significantly impact survival in patients with advanced malignancies. Traditional treatment options for GOO can be broadly divided into surgical [surgical gastrojejunostomy (GJ)] and endoscopic interventions (dilation and/or placement of luminal self-expanding metal stents). While surgical GJ has been shown to provide a more lasting relief of symptoms when compared to luminal stenting, it has also been associated with a higher rate of adverse events. Furthermore, many patients with advanced metastatic disease are not good surgical candidates. More recently, endoscopic ultrasound (EUS)-guided GJ has emerged as a potential alternative to traditional surgical and endoscopic approaches. This review focuses on the new advances and technical aspects of EUS-GJ and clinical outcomes in the management of both benign and malignant disease.

Background Unlike other anti–tumor necrosis factor alpha antibodies, golimumab does not deliver on its promise of effectiveness for treating patients with ulcerative colitis. We investigated the value of therapeutic drug monitoring for optimizing golimumab therapy. Methods We analyzed the golimumab pharmacokinetics data of 56 patients with moderate to severe ulcerative colitis. Induction and maintenance golimumab concentrations (296 venipuncture, 414 serum) were used to develop a population pharmacokinetic model. Exposure–response relationships were analyzed using the data of 40/56 patients with available endoscopy data. Receiver operating characteristic curve analysis was performed, and an exposure–response Markov model was developed, linking golimumab exposure to probabilities of transitioning between Mayo endoscopic subscore (MES) states from baseline to week (w)14. Results Golimumab pharmacokinetics was best described by a 2-compartment model with linear absorption and elimination. Antibodies to golimumab and previous biological therapy reduced golimumab exposure. Still, interindividual pharmacokinetic variability (IIVPK) remained largely unexplained. Endoscopic remission (ER; MESw14 ≤ 1) was achieved in 14/40 (35%) patients. Golimumab serum trough concentration thresholds of 7.4 mg/L (w6) and 3.2 mg/L (w14) predicted ER at w14 (positive predictive values [pv+] 83% and 91%, pv- 82% and 67%, respectively). The 3.2-mg/L target predicted 38% and 44% chances of achieving ER in patients with MESbaseline of 3 and 2, respectively. Conclusions Personalized, model-based induction dosing aiming at here-established target concentrations may account for IIVPK and thus provide patients with more equal chances of achieving ER. As <50% of patients attained the exposure targets, higher golimumab induction dosing requires investigation to secure its future in clinical practice.

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BackgroundStored red blood cells (RBCs) accumulate biochemical and biophysical changes, known as storage lesion. The aim of this study was to re-challenge current data that anaemia in chronically anaemic haematology patients is not associated with low skeletal muscle tissue oxygen (StO2), and that RBC storage age does not influence the tissue response after ischaemic provocation, using near-infrared spectroscopy.Patients and methodsTwenty-four chronic anaemic haematology patients were included. Thenar skeletal muscle StO2 was measured at rest (basal StO2), with vascular occlusion testing (upslope StO2, maximum StO2) before and after transfusion.ResultsBasal StO2 was low (53% ± 7%). Average RBC storage time was 10.5 ± 3.9 days. Effects of RBC transfusions were as follows: basal StO2 and upslope StO2 did not change significantly; maximum StO2 increased compared to baseline (64 ± 14% vs. 59 ± 10%, p = 0.049). Change of basal StO2, upslope StO2 and maximum StO2 was negatively related to age of RBCs. The decrease of maximum StO2 was predicted (sensitivity 70%, specificity 100%), after receiving RBCs ≥ 10days old.DiscussionResting skeletal muscle StO2 in chronic anaemic patients is low. RBC storage time affects skeletal muscle StO2 in the resting period and after ischaemic provocation.