Publications by authors named "Wouter Ten Voorde"

3 Publications

  • Page 1 of 1

Intradermal lipopolysaccharide challenge as an acute in vivo inflammatory model in healthy volunteers.

Br J Clin Pharmacol 2021 Jul 22. Epub 2021 Jul 22.

Centre for Human Drug Research, Leiden, the Netherlands.

Aims: Whereas intravenous administration of Toll-like receptor 4 ligand lipopolysaccharide (LPS) to human volunteers is frequently used in clinical pharmacology studies, systemic use of LPS has practical limitations. We aimed to characterize the intradermal LPS response in healthy volunteers, and as such qualify the method as local inflammation model for clinical pharmacology studies.

Methods: Eighteen healthy male volunteers received 2 or 4 intradermal 10 ng LPS injections and 1 saline injection on the forearms. The LPS response was evaluated by noninvasive (perfusion, skin temperature and erythema) and invasive assessments (cellular and cytokine responses) in skin biopsy and blister exudate.

Results: LPS elicited a visible response and returned to baseline at 48 hours. Erythema, perfusion and temperature were statistically significant (P < .0001) over a 24-hour time course compared to saline. The protein response was dominated by an acute interleukin (IL)-6, IL-8 and tumour necrosis factor response followed by IL-1β, IL-10 and interferon-γ. The cellular response consisted of an acute neutrophil influx followed by different monocyte subsets and dendritic cells.

Discussion: Intradermal LPS administration in humans causes an acute, localized and transient inflammatory reaction that is well-tolerated by healthy volunteers. This may be a valuable inflammation model for evaluating the pharmacological activity of anti-inflammatory investigational compounds in proof of pharmacology studies.
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July 2021

Comprehensive evaluation of microneedle-based intradermal adalimumab delivery vs. subcutaneous administration: results of a randomized controlled clinical trial.

Br J Clin Pharmacol 2021 Aug 2;87(8):3162-3176. Epub 2021 Feb 2.

Department of Pediatric Rheumatology Willem-Alexander Children's Hospital, Leiden University Medical Center, Leiden, the Netherlands.

Aims: To evaluate feasibility of intradermal (i.d.) adalimumab administration using hollow microneedles, and to compare a single i.d. dose of adalimumab using a hollow microneedle with a single subcutaneous (s.c.) dose using a conventional needle.

Methods: In this single-centre double-blind, placebo-controlled, double-dummy clinical trial in 24 healthy adults we compared 40 mg adalimumab (0.4 mL) administered i.d. using a hollow microneedle with a s.c. dose using a conventional needle. Primary parameters were pain, acceptability and local tolerability; secondary parameters safety, pharmacokinetics and immunogenicity. We explored usability of optical coherence tomography, clinical photography, thermal imaging, and laser speckle contrast imaging to evaluate skin reaction after i.d. injections. In vitro protein analysis was performed to assess compatibility of adalimumab with the hollow microneedle device.

Results: While feasible and safe, injection pain of i.d. adalimumab was higher compared to s.c. adalimumab (35.4 vs. 7.9 on a 100-point visual analogue scale). Initial absorption rate and relative bioavailability were higher after i.d. adalimumab (time to maximum plasma concentration = 95 h [47-120]; F = 129% [6.46%]) compared to s.c. adalimumab (time to maximum plasma concentration = 120 h [96-221]). Anti-adalimumab antibodies were detected in 50% and 83% of the subjects after i.d. and s.c. adalimumab, respectively. We observed statistically significantly more erythema and skin perfusion after i.d. adalimumab, compared to s.c. adalimumab and placebo injections (P < .0001). Cytokine secretion after whole blood lipopolysaccharide challenge was comparable between administration routes.

Conclusions: Intradermal injection of adalimumab using hollowing microneedles was perceived as more painful and less accepted than s.c. administration, but yields a higher relative bioavailability with similar safety and pharmacodynamic effects.
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August 2021

The effect of repeated methotrexate injections on the quality of life of children with rheumatic diseases.

Eur J Pediatr 2019 Jan 17;178(1):17-20. Epub 2018 Nov 17.

Department of Pediatric Rheumatology Willem-Alexander Children's Hospital, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.

In clinical practice, the burden of repeated injections in children with rheumatic disease receiving disease-modifying anti-rheumatic drugs is significant. To investigate the nature and extent of impact on the quality of life after repeated injections, we conducted a literature review. Two relevant papers were identified, both about children with juvenile idiopathic arthritis (JIA) being administered methotrexate. The results suggest that the combination of needle fear, impact of methotrexate treatment, and procedural consequences, e.g., blood sampling, all contribute to the distress and the loss of quality of life of children with JIA. Remarkably, no studies examining fear of injections or injection pain in children with rheumatic diseases receiving biologicals were identified.Conclusion: Strategies to optimize administration of disease modifying anti-rheumatic drugs should be systematically investigated. What is Known: • Repeated parenteral administration of drugs is burdensome for children with rheumatic diseases. What is New: • Needle fear should be investigated systematically to optimize administration of disease-modifying anti-rheumatic drugs.
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January 2019