Background/Purpose: Apremilast (APR), a PDE4 inhibitor,
helps regulate immune responses in psoriatic arthritis (PsA). PALACE 1, 2, and 3 compared apremilast
(APR) efficacy/safety with placebo (PBO) in patients (pts) with active PsA
despite prior conventional DMARDs and/or biologics, including efficacy
assessments across multiple disease aspects. Enthesitis and dactylitis,
hallmark features of PsA, lead to pain and disability. We report the impact of
APR treatment over 104 wks on enthesitis and dactylitis in a pooled analysis of
the PALACE 1-3 studies.

Methods: Pts were randomized (1:1:1) to PBO, APR 30 mg BID (APR30),
or APR 20 mg BID (APR20) stratified by baseline DMARD use (yes/no). The PBO-controlled
phase continued to Wk 24, with an early escape option at Wk 16. At Wk 24, all remaining
PBO pts were re-randomized to APR30 or APR20. Double-blind APR treatment
continued to Wk 52; pts could then continue to receive APR for up to an
additional 4 years during an open-label extension phase. Data were pooled
across PALACE 1-3 at Wk 24, as prespecified in the protocol, to allow for
analysis of robust numbers of pts with pre-existing enthesopathy and/or
dactylitis. Enthesitis was evaluated based on the Maastricht Ankylosing
Spondylitis Enthesitis Score (MASES) (range: 0-13), which indicates the number
of painful entheses out of 13 entheses sites. The dactylitis count (range:
0-20) is the number of digits (hands/feet) with dactylitis present; each digit
is rated as 0 (absence) or 1 (presence). Analyses
at Wk 24 used last observation carried forward for missing values; Wk 52 and Wk
104 were based on data as observed.

Results: At Wk 24, mean change in MASES was
-1.3 (APR30, P=0.0194 vs PBO), -1.2 (APR20), and -0.9 (PBO); MASES=0 was
achieved by 27.5% (APR30), 27.4% (APR20), and 22.5% (PBO) of pts. Mean change
in dactylitis count was -1.8 (APR30, P=0.0097 vs PBO), -1.6 (APR20), and
-1.3 (PBO); dactylitis count of 0 was achieved by 46.2% (APR30), 45.9% (APR20),
and 39.0% (PBO) of pts. Long-term improvement in enthesitis and dactylitis
severity was seen in pts with enthesitis and/or dactylitis at baseline who were
receiving APR at 104 wks, as shown by reductions in MASES and dactylitis counts
(Table). Mean % changes in MASES were -57.5% (APR30) and -55.1% (APR20) at Wk 104.
MASES of 0, indicating no pain at any of the entheses assessed, was achieved by
48.7% (APR30) and 51.5% (APR20) of pts. Mean % changes in dactylitis count were
-80.0% (APR30) and -75.8% (APR20) at Wk 104. Dactylitis counts decreased to 0 in
77.5% (APR30) and 72.9% (APR20) of pts. Over 104 wks, most AEs were mild or moderate
in severity; in general, no increase was seen in AE incidence and severity with
longer term exposure.

Conclusion:
Over 104 wks, APR
continued to demonstrate efficacy in PsA treatment, including improvements in
enthesitis and dactylitis. APR
demonstrated an acceptable safety profile and was generally well tolerated for
up to 104 wks.