Favourable pharmacokinetics of intradermal adalimumab over subcutaneous
administration: results of a randomized controlled trial
Aim 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 (OCT), clinical
photography, thermal imaging, and laser speckle contrast imaging (LSCI)
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 101-point VAS scale). Initial absorption rate and
bioavailability were higher after i.d. adalimumab (Tmax=95h(47-120);
F=129%(6.46%)) compared to s.c. adalimumab (Tmax=120h(96-221)). In
50% and 83% of the subjects anti-adalimumab antibodies were detected
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<0.0001).
Cytokine secretion after whole blood LPS challenge was comparable
between administration routes. Conclusion Intradermal of adalimumab
using hollowing microneedles was perceived as more painful, and less
accepted than s.c. administration, however, yields a higher
bioavailability with similar safety and pharmacodynamic effects.