Pain, acceptability, and local tolerability after i.d. and s.c. adalimumab administration
Pain ascribed to needle injections is often divided into insertion pain which is pain resulting from the needle insertion, and injection pain which is pain resulting from the fluid injection. Insertion pain, injection pain, and post-injection pain were quantified using both a 100 points visual analogue scale (VAS) and the Dutch Faces Pain Scales Revised (FPSR, (15)). Insertion pain did not statistically significant differ between a hollow microneedle and a regular s.c. needle (Figure 2A , all p=0.22). Pain associated with fluid injection was higher for i.d. versus s.c. injections (Figure 2A , i.d. versus s.c. estimated means 29.5 and 8.3, decrease of 72%, 95% confidence interval (CI) -83% -53%, p<0.001). Intradermal adalimumab injections were more painful (estimated mean 35.4) than s.c. adalimumab injections (estimated mean 7.9). Comparing the treatments (placebo versus adalimumab, with both i.d. and s.c. administration methods combined) no statistically significant difference was observed (p=0.55). There was no difference within the administration method between adalimumab or placebo administration (placebo versus adalimumab within administration method p=0.32 and p=0.81 for i.d. and s.c., respectively). No pain was reported 24 hours after injection in any treatment group (Figure 2B ). For both insertion and injection pain a similar pattern in pain was reported in the FPSR in comparison with the VAS (data not shown). Altogether these subject reported outcomes indicate that there is no difference in pain between adalimumab and placebo injection, but that i.d. injection is more painful than s.c. injection.
To determine which injection type was preferred, subjects were asked about their preference: immediately after the injections (i.e., before seeing the injection area) and a day after the injections. Subject reported outcomes indicated that subjects had a preference for s.c. injection compared to i.d. injection (Figure 2C ). They also preferred to receive a hypothetical next injection using s.c. rather than i.d. administration (Figure 2D ). Directly after injection a majority (13 subjects, 54%) indicated no fear, while 24 hours after injection most (19, 79%) subjects indicated no fear after injection. To summarize, we found that volunteers prefer s.c. over i.d. injection.