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Background and Objective: Efficacy of infliximab in children with inflammatory bowel disease can be enhanced when serum concentrations are measured and further dosing is adjusted to achieve and maintain a target concentration. Use of a population pharmacokinetic model may help to predict an individual's infliximab dose requirement. The aim of this study was to evaluate the predictive performance of available infliximab population pharmacokinetic models in an independent cohort of Dutch children with inflammatory bowel disease., Methods: In this retrospective study, we used data of 70 children with inflammatory bowel disease (443 infliximab concentrations) to evaluate eight models that focused on infliximab pharmacokinetic models in individuals with inflammatory bowel disease, preferably aged ≤ 18 years. Predictive performance was evaluated with prior predictions (based solely on patient-specific covariates) and posterior predictions (based on covariates and infliximab trough concentrations). Model accuracy and precision were calculated with relative bias and relative root mean square error and we determined the classification accuracy at the trough concentration target of ≥ 5 mg/L., Results: The population pharmacokinetic model by Fasanmade was identified to be most appropriate for the total dataset (relative bias before/after therapeutic drug monitoring: -20.7%/11.2% and relative root mean square error before/after therapeutic drug monitoring: 84.1%/51.6%), although differences between models were small and several were deemed suitable for clinical use. For the Fasanmade model, sensitivity and specificity for maximum posterior predictions for the next infliximab trough concentration to be ≥ 5 mg/L were respectively 83.5% and 80% with an area under the receiver operating characteristic curve of 0.870., Conclusions: In our paediatric cohort, various models provided acceptable predictive performance, with the Fasanmade model deemed most suitable for clinical use. Model-informed precision dosing can therefore be expected to help to maintain infliximab trough concentrations in the target range., (© 2024. The Author(s).)

Objective: To evaluate the safety and effectiveness of chenodeoxycholic acid (CDCA) treatment in patients with cerebrotendinous xanthomatosis (CTX)., Methods: Two retrospective cohort studies were conducted in CTX patients who underwent CDCA treatment: one in the Netherlands (NL; CDCA-STUK-15-001) and one in Italy (IT; CDCA-STRCH-CR-14-001). Eligible patients were aged 2-75 years, had been diagnosed with CTX, and were treated with CDCA orally for ≥1 year. The impact of CDCA treatment on biochemical markers (including serum cholestanol levels) and disease signs and symptoms were assessed, in addition to the safety and tolerability of CDCA treatment., Results: A total of 35 patients were screened in the NL study and were diagnosed with CTX at 25.6 (± 13.7 SD) years on average. These patients were treated with CDCA and followed up for a median of 9.00 (range: 0.4-26.3) years. In addition, 28 patients were enrolled in the IT study and were diagnosed at 35.0 (± 11.4 SD) years on average (median duration of CDCA treatment: 5.75 [range: 0.0-25.0] years). Signs and symptoms of disease resolved, improved, or remained stable in many patients, with concomitant improvements in biochemical marker levels (serum cholestanol, p < 0.001; 7α-hydroxy-4-cholesten-3-one, p < 0.001 [IT study])., Conclusions: The outcomes of these retrospective cohort studies indicate that CDCA is effective in the long-term treatment of CTX, with an acceptable safety profile.

Objective: Infliximab maintenance treatment for Crohn's disease (CD) consists of intravenous infusions that are usually given at 6-8-week intervals. We aimed to evaluate whether home-based infliximab infusions could offer a useful and safe alternative for the management of CD patients., Methods: Adult CD patients receiving infliximab maintenance treatment at the Academic Medical Center in Amsterdam were invited to receive their infusions at home for the duration of 1 year. Patients had to be in clinical remission and should have had no adverse events during previous infusions. Patient satisfaction and experience were studied. Costs were analyzed and compared with hospital-based infliximab infusions., Results: Twenty-nine patients were invited, of whom 13 (45%) wanted to participate. Of the participants, 54% were female, and the median age was 33 years. In total, 59 infliximab infusions were administered at home at a median dose of 360 mg. The median rating of patient satisfaction was 8 on a scale from 1 to 10 for both home and hospital treatment settings. An important observation was that patients' willingness to participate would have been 70% if the possibility of receiving infusions at home outside office hours had been offered. Costs of infliximab infusions at home were €229 per infusion compared with €284 at the infusion clinic (excluding drug costs)., Conclusion: Home-based infliximab infusions were associated with a cost saving of €55 per infusion. Most participants were satisfied and would recommend home-based infusions to others. Infliximab treatment at home might be recommended as routine care for CD patients.

Background: Improved compliance in active ulcerative colitis (UC) is likely to improve healthcare efficiency by reducing time spent in active mild to moderate UC state. To establish whether once daily (OD) mesalazine offers economic advantages over twice daily (BD) dosing in active UC, we evaluated the outcomes and costs of a recently published randomized study., Methods: A cost-effectiveness model with four week Markov cycles was developed to reflect current treatment practices in the Netherlands with OD and BD mesalazine for active UC. The health service perspective of the Netherlands was reflected in the model and considered a 32week time horizon with 4 weekly Markov cycles. Outcomes evaluated in the model were time spent in active and remission UC and the corresponding health-related quality of life associated with different clinical states. This was then used to derive quality adjusted life-years (QALYs) at each treatment stage., Results: A greater proportion of subjects on 4 g OD achieved remission at weeks 4 and 8 compared with 2g BD. After 32 weeks the average costs per patient with active UC were €3097 and €3548 for those treated with OD and BD mesalazine respectively, with an average saving of €451 per patient treated with OD mesalazine. The average costs per QALY for OD and BD mesalazine were €5433 and €6324 for OD and BD, respectively., Conclusions: Based on the results from a single randomized study, OD dosing resulted in a shorter time spent in active UC which resulted in lower healthcare costs., (© 2013 Elsevier B.V. All rights reserved.)

Purpose: Plant sterol (PS)-enriched food products are known to reduce plasma cholesterol concentrations by inhibiting the absorption of dietary and biliary cholesterol. The physiological responses induced by food intake in the gastrointestinal tract are all important factors in determining the overall effect of PS. The aim of this study was therefore to assess the effect of timing of consumption of a plant sterol (PS)-containing yoghurt drink relative to meal ingestion on gastric emptying (GE) of the drink and gallbladder (GB) volume., Methods: This is a randomized, single-centre, controlled study with crossover design in 12 healthy male volunteers. Three treatments were tested; a 100 mL PS yoghurt drink (labeled with 1,000 mg acetaminophen) was consumed 45 min prior to, during and 45 min after a solid meal. Plasma samples were taken, and gallbladder volumes were measured at baseline and at regular intervals during a 6-h study period., Results: When consumed before the consumption of a meal, the yoghurt drink exhibited fast GE. The solid meal intake caused a significant contraction of the gallbladder. Consumption of the PS drink before the meal had no significant effect on GB volume as compared to baseline and compared to during and after meal consumption., Conclusions: The PS-containing drink, which empties fast from the stomach, does not sufficiently trigger gallbladder contraction without co-ingestion of a solid meal and in consequence does not induce the necessary physiological changes needed to allow PS to exhibit their effect on inhibiting cholesterol absorption.

Background: Thioguanine has been used for the treatment of inflammatory bowel disease, in particular for patients who failed conventional thiopurine therapy. To date, thioguanine has been infrequently studied in ulcerative colitis., Aim: To evaluate the tolerability, safety and efficacy of thioguanine in the treatment of ulcerative colitis., Methods: A database analysis was performed on inflammatory bowel disease patients who had failed conventional thiopurine therapy and were treated with thioguanine. Rates and reasons for treatment failure were assessed. Laboratory values, abdominal ultrasonography, liver biopsy and endoscopic remission rates were evaluated., Results: Forty-six patients were included and median treatment duration was 22 months (range 0.3-72.0). Nine patients failed thioguanine therapy: six due to adverse events, three due to therapy resistance. Concomitant treatment with aminosalicylates protected against thioguanine failure (hazard ratio (HR) 0.11, 95% CI 0.03-0.48). When performed, ultrasonography (n = 21) revealed no suspected therapy-related pathology in all but one patient, in whom hepatomegaly was observed. Liver histology (n = 12) predominantly revealed no abnormalities (n = 4) or non-specific regeneration (n = 4); none showed nodular regenerative hyperplasia. At follow-up, 40% of colonoscopies revealed endoscopic remission as compared with 10% at baseline (P = 0.180)., Conclusions: Long-term use of thioguanine appears to be well tolerated and relatively safe in ulcerative colitis patients who failed conventional thiopurine therapy., (Copyright © 2010 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

The aim of this study was to report the 1-year clinical experience with infliximab treatment for Crohn's disease (CD) in the Netherlands. All 73 CD patients receiving infliximab infusions were prospectively followed during 1 year after the drugs' registration in the Netherlands. Clinical response and adverse events were assessed for both active luminal disease as well as fistulous disease. A total of 212 infusions were administered to 57 patients with active luminal CD and 16 patients with fistulous CD. The mean duration between infusions was 60 days. In 17% of patients, adverse events were recorded, of which one was serious. The response rate was 81% in active luminal CD and 87% in fistulous disease. Response rates were highest in patients receiving concomitant methotrexate as maintenance therapy. Steroids could successfully be tapered off in 73% of responding luminal CD patients and 100% of responding CD patients with fistulae. Eleven patients showed a loss of response to continuous infliximab readministration. Our clinical experience with infliximab for active luminal and fistulous CD showed that the administration is safe, effective, and has high steroid-sparing efficacy. Higher response rates were seen with methotrexate as concomitant medication.