An article by Marieke Zijlstra et al at Sanguin in the Netherlands published in the January 2021 issue of the Journal of Pediatric Gastroenterology and Nutrition reports on a pilot bridging study of inflammatory bowel disease in children that compared capillary samples to paired venous sera.
With this study, the research team was able to conclude that dried blood sampling using Mitra devices with VAMS was a good candidate for measuring IFX blood levels in pediatric patients and would facilitate home sampling for therapeutic drug monitoring (TDM).
Cytokines play a key role in inflammatory bowel disease (IBD). Tumor necrosis factor-alpha (TNFα) is a cytokine produced primarily from macrophages. Macrophages are immune cells that are an essential part of the innate immune system. TNFα plays a key role in a number of conditions such as lesions, tumor development, infection and inflammation.
When released from host macrophages, TNFα activates further inflammatory responses, such as the release of other proinflammatory cytokines. Moreover, TNFα has a direct effect on the intestinal epithelial barrier disrupting intestinal tight junctions. In doing so, the cytokine acts to increase inflammation of the gut and, in some cases, leads to inflammatory bowel disease (IBD). IBD is a term often used to describe two conditions: ulcerative colitis (large intestine only) and Crohn’s disease (which can affect any part of the digestive system.
There are a number of drugs with anti-TNFα activity, and these include infliximab (IFX) and adalimumab (ALD). Both drugs are monoclonal antibodies (mAbs), which act to neutralize the function of TNFα preventing it from binding to its receptors. Both drugs have been shown to be very effective in treating IBD in both adults and children.
For children, information on dosing of these mAb drugs is limited to extrapolating from adult data, which is not sufficient to provide accurate and individualized dosing. Indeed, it is critical to get the dose right for each individual, as low dose levels have been associated with a loss of therapeutic response. In their study paper, the authors quote a previous study where pediatric “patients with trough levels during maintenance treatment of 5 µg/mL [of IFX] are more likely to show a clinical response.”
Therapeutic drug monitoring (TDM) of children on IFX is currently conducted in clinic by venipuncture. To minimize the number of needle sticks, TDM is often done during the same appointment or time of the next administration of infliximab. This means that any dose adjustments must wait until the next drug infusion appointment, which could be every few weeks and is not ideal. Use of dried blood sampling can be performed more frequently and outside of the hospital, which could help with optimizing dosing and more individualized and timely administration of IFX.
The authors highlighted that dried blood samples (both VAMS and dried blood spots) had been previously demonstrated in adult cohorts to monitor IFX levels. An investigation of the application of dried blood sampling had not yet been demonstrated in children undergoing TDM of IFX. The aim of this study was to compare venipuncture to dried microsamples with pediatric inflammatory bowel disease (PIBD) patients.
This work provides another example of the importance of bridging between capillary and venous blood. It also demonstrates the utility of home sampling to provide the potential for improving treatment by allowing for sampling in advance of IV administration of a drug rather than during the same appointment.
Furthermore, finger-stick sampling appears to be a less stressful specimen collection approach than venipuncture for pediatric patients and study subjects. Indeed, a few years ago, Christophe Stove’s group at Ghent University ran a survey on adults and children in their study where finger-stick microsampling with Mitra-VAMS devices were the preferred choice compared to venipuncture and dried blood spot (DBS).
In terms of HCT correction, it is interesting to see that both an average HCT and per person HCT correction gave an almost identical correction. However, I agree with the authors that this must be approached with caution, especially where cohorts are expected to have a wide HCT range.
To learn more about how microsampling is being applied in Therapeutic Drug Monitoring visit out Resources Page.
This study paper was summarized for our readers by James Rudge, PhD, Neoteryx Technical Director. This is curated content. To learn more about the important research outlined in this review, visit the original article published in the Journal of Pediatric Gastroenterology and Nutrition.
Image Credits: IBD, IBS image iStock, Neoteryx