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

Abstract

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 rel = 129% [6.46%]) compared to s.c. adalimumab (time to maximum plasma concentration = 120 h ). Antiadalimumab antibodies were detected in 50% and 83% of the subjects after i.d. and s.c. adalimumab, respectively. We observed statistically significantly more erythemaThe authors confirm that the PI for this paper is Jacobus Burggraaf and that he had direct clinical responsibility for the healthy volunteers in this study.Justin Jacobse and Wouter ten Voorde Shared first authorship.Robert Rissmann and Rebecca ten Cate Shared last authorship.

Exploiting Unique Features of Microneedles to Modulate Immunity

“…Second, in certain cases, MNA has caused skin irritation at the site of application compared to SC injection in humans immediately after application. [ 237 ] This is likely due to the disruption of the epidermis, which contains LCs, important for maintaining homeostasis through tolerizing properties after infection. Additionally, Phase 1 clinical trials show that there are higher levels of circulating cytokines implicated in allergic reactions (IL‐5 and IL‐13) in MNA‐treated patients compared to those treated I.M., which similarly led to short‐term irritation at the site of application.…”

A multimodal, comprehensive characterization of a cutaneous wound model in healthy volunteers

“…Skin blood perfusion was quantified using Dynamic Optical Coherence Tomography (D-OCT; VivoSight OCT, Michelson diagnostics) at baseline and on each study day visit as described before. 22,23 Subjects were acclimatized to a temperature-controlled room and lighting was kept constant for the entire duration of the…”

“…Skin erythema was quantified using multispectral imaging (Antera 3D®, Miravex), as described in detail before. 22,23,25 The multispectral camera creates a closed chamber of 25 cm 2 for image capture with standardized lighting and distance. A region of interest of 4 mm in diameter was defined and kept analogous with all analysed images.…”

“…The need to find effective treatment options for acute and chronic wounds is unmet. The financial burden to treat chronic wounds is estimated to be approximately $ [15][16][17][18][19][20][21][22] billion by the end of 2024. 13,14 In the last five years, only a limited number of clinical trials have been performed focusing on a novel treatment for wounds using an evidence-based approach.…”

Preparation and characterization of flexible furosemide-loaded biodegradable microneedles for intradermal drug delivery

“…drug delivery has emerged as a better alternative to s.c. routes across different therapeutic agents, such as insulin 20 and monoclonal antibodies. 21 Data regarding the feasibly of i.d. delivery of FUR using MNs are scarce.…”