Background/Purpose: Apremilast (APR), an oral
phosphodiesterase 4 inhibitor, has demonstrated clear efficacy and good
tolerability in psoriatic arthritis (PsA) and psoriasis. Longer term data are
crucial for chronic diseases such as PsA. PALACE 1 compared APR efficacy and safety
with placebo (PBO) in patients with active PsA despite prior conventional disease-modifying
antirheumatic drugs (DMARDs) and/or biologics. We evaluated the longer term efficacy
and safety of APR treatment over 156 weeks.

Methods: Patients 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 Week 24, with an early escape option at Week 16. At Week 24, all
remaining PBO patients were re-randomized to APR30 or APR20. Double-blind APR treatment
continued to Week 52; patients could continue APR for up to 4 additional years.
Efficacy assessments in Years 2 and 3 were conducted at Weeks 65, 78, 91, 104, 117,
130, 143, and 156.

Results: 504 randomized patients received
≥1 dose of study medication
(PBO: n=168; APR30: n=168; APR20: n=168). In an “as observed” analysis, 53.2%
of APR30 patients
and 59.6% of APR20
patients achieved
a modified
ACR20 response at Week 52 (Table), regardless of whether APR was started at
Week 0, 16, or 24; 65.3% (APR30) and 60.9% (APR20) of patients showed these
responses at Week 104. Of the patients entering the third year of therapy, 92%
(260/284) completed the Week 156 visit; this is overall 52% (260/504) of
patients randomized at baseline. Patients receiving APR at Week 156 demonstrated sustained
improvements, as shown by ACR20/ACR50/ACR70 response rates modified for PsA by
the addition of the distal interphalangeal joints of the toes and the
carpometacarpal joints to the total joint count, swollen/tender joint count mean
percent improvement, HAQ-DI mean change, proportion of patients with HAQ-DI
exceeding the minimal clinically important difference (MCID) ≥0.30 threshold, mean change
in DAS-28 (CRP), achievement of DAS (CRP) <2.6, and PASI-50/PASI-75
responses (Table). No new safety concerns were identified with up to 156 weeks
of APR treatment. During
Weeks >104 to ≤156 of APR exposure, the only adverse event (AE) occurring in ≥5%
of patients was upper respiratory tract infection; most AEs were mild/moderate
in severity. Diarrhea (2.1%) and nausea (2.1%) occurred at low rates in Weeks >104 to ≤156. Serious AEs occurred in 6.9%
(APR30) and 6.4% (APR20) of patients, and few discontinuations (0.7%) due to
AEs occurred over Weeks >104 to ≤156.

Conclusion: Over 156 weeks, among patients
remaining in the study on treatment, APR demonstrated sustained and clinically
meaningful improvements in PsA signs/symptoms, including physical function and
associated psoriasis. APR continued to demonstrate an acceptable safety profile
and was generally well tolerated.