Study design
This was a single-center double-blind, placebo-controlled, double-dummy
clinical trial with four interventions: i.d. adalimumab (40 mg Humira,
AbbVie, Maidenhead, UK), i.d. saline (0.9%), s.c. adalimumab, and s.c.
saline. i.d. injections were given using a hollow microneedle
(MicronJet600 from Nanopass Technologies Ltd., Ness Ziona, Israel), s.c.
injections using a regular needle (Microlance 3 from Becton, Dickenson,
and Company (BD), Franklin Lakes, United States of America); both
devices were connected to a syringe (1 mL Luer-LokTM,
BD). The length of the three needles of a MicronJet600 device is 600 µm.
Injections were given according to standard operating procedures and the
manufacturer’s instruction. All subjects received one placebo injection
and one adalimumab injection of 40 mg in 0.4 ml in the right and left
upper lateral thigh by the same physician. Given the nature of the
study, the physician administering the injection could not be blinded to
the method of administration but was blinded to treatment, i.e.,
adalimumab or placebo. Therefore, this physician was not involved in the
assessment of any of the pre-defined outcomes (evaluator-blinded). The
subjects were in a prone position during and in between injections to
ensure blinding (subject-blinded). Injections were spaced five minutes
apart. Prior to administration, the sites of injection were annotated
using a surgical marker (Purple Surgical, Shenley, England). Subjects
were instructed to maintain the marking while at home, and to prevent
excessive sun exposure to the injection site to limit possible
interference with the exploratory measurements.