TY - JOUR
T1 - Comprehensive evaluation of microneedle-based intradermal adalimumab delivery vs. subcutaneous administration: results of a randomized controlled clinical trial
AU - Jacobse, Justin
AU - ten Voorde, Wouter
AU - Tandon, Anushka
AU - Romeijn, Stefan G.
AU - Grievink, Hendrika W.
AU - van der Maaden, Koen
AU - van Esdonk, Michiel J.
AU - Moes, Dirk Jan A. R.
AU - Loeff, Floris
AU - Bloem, Karien
AU - de Vries, Annick
AU - Rispens, Theo
AU - Wolbink, Gertjan
AU - de Kam, Marieke
AU - Ziagkos, Dimitrios
AU - Moerland, Matthijs
AU - Jiskoot, Wim
AU - Bouwstra, Joke
AU - Burggraaf, Jacobus
AU - Schrier, Lenneke
AU - Rissmann, Robert
AU - ten Cate, Rebecca
N1 - Funding Information: Wim Jiskoot is a scientific advisor at Coriolis Pharma, Martinsried. Theo Rispens received fees for lectures from Pfizer, AbbVie and Regeneron, and a research grant from Genmab. Koen van der Maaden is scientific advisor of MyLife Technologies B.V. and co‐founder of uPRAX microsolutions B.V. The other authors have declared no conflict of interest exists. Funding Information: We are indebted to our volunteers, and thankful to the team at the Centre for Human Drug Research and the pharmacy of the Leiden University Medical Center. Thanks to Karen Broekhuizen, medical writer at the Centre for Human Drug Research, who edited the manuscript for clarity. Funding: Dutch Arthritis Foundation: BP15?1-262. Publisher Copyright: © 2021 The Authors. British Journal of Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of British Pharmacological Society. Copyright: Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/8
Y1 - 2021/8
N2 - 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 rel = 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.
AB - 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 rel = 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.
KW - adalimumab
KW - intradermal
KW - microneedle
KW - pain
KW - subcutaneous
UR - http://www.scopus.com/inward/record.url?scp=85100133130&partnerID=8YFLogxK
U2 - https://doi.org/10.1111/bcp.14729
DO - https://doi.org/10.1111/bcp.14729
M3 - Article
C2 - 33403697
SN - 0306-5251
VL - 87
SP - 3162
EP - 3176
JO - British journal of clinical pharmacology
JF - British journal of clinical pharmacology
IS - 8
ER -