English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Background Therapeutic drug monitoring of ustekinumab (UST), a monoclonal antibody directed against the p40 subunit of IL12/23, can serve as a tool to identify underexposed Crohn’s disease (CD) patients, as UST concentrations have been linked to treatment response. Drug concentrations are most often measured when a patient is losing response. To reduce the risk of loss of response, drug concentrations could be measured upfront to predict the chance of achieving response later on and optimising treatment if necessary. Identification of the optimal time point to measure UST levels that have a predictive value for long-term outcome requires studies with multiple sampling. Dried blood spot (DBS) sampling allows convenient and remote collection of a blood drop through a small finger prick. The current study aimed to develop and validate the DBS method in order to identify the best time point to measure UST concentrations to predict long-term outcome in CD patients and explore the pharmacokinetic profile. Methods UST concentrations (0.2–80 μg/ml) were spiked in citrated whole blood and 40 μl was spotted onto protein saver cards. After punching a 6mm disc, DBS was extracted and the UST concentration was measured with an in-house developed MA-UST56A2D11/MA-UST56C1H12 ELISA. The extraction efficiency, accuracy, precision and the effect of anti-UST antibodies on UST detection were evaluated. Additionally, the effect of the spotted blood volume, the stability of the DBS card at room temperature (RT) and DBS extract at -20°C was examined. To evaluate the correlation between UST in DBS extracts and serum, DBS and serum were simultaneously collected from 8 UST-treated CD patients at two different time points. Results Spiking UST to citrated whole blood and subsequent spotting and extraction revealed an average extraction efficiency of 65 ± 9% (n = 11). The accuracy and imprecision of all concentrations tested were 92–109% and 11–18%, respectively. Addition of anti-UST antibodies to spiked UST samples caused a similar decrease in UST concentration in DBS extracts as in serum. Spotted blood volumes between 15 and 50 μl demonstrated similar recoveries. Storing the DBS card at RT for up to 2 weeks and DBS extract at -20°C for 2 months did not impair recovery. UST concentrations in DBS extracts (range: 0.55–12.1 μg/ml) from CD patients correlated strongly with those in serum (Pearson r = 0.982, p &amp;lt; 0.0001). Conclusion DBS is a robust method that facilitates multiple sampling for the determination of UST concentrations in CD patients. To explore the pharmacokinetic profile of UST and identify the best time point during induction to predict the long-term outcome, a prospective study in which multiple DBS are collected in active CD patients initiating UST is warranted.

journal of crohn's and colitis

P601 Development and validation of dried blood spot sampling as a tool to identify the best time point to measure predictive ustekinumab serum concentrations in patients with Crohn’s disease