SAN DIEGO, CA—Patients with active psoriatic arthritis treated with apremilast reported clinically meaningful improvements in signs and symptoms and physical function over 52 weeks compared with placebo, according to results of the Phase 3 randomized PALACE 3 trial presented at the 2013 ACR/ARHP Annual Meeting.
In addition, apremilast demonstrated an acceptable safety profile and was generally well tolerated, Christopher J. Edwards, MD, of the University of Southampton, Southampton, UK, and colleagues, noted.
Apremilast is an oral phosphodiesterase 4 inhibitor that modulates inflammatory mediators. The PALACE 3 trial compared the efficacy and safety of apremilast with placebo in patients with active psoriatic arthritis and at least 1 psoriatic lesion ≥2cm at baseline despite prior use of disease-modifying antirheumatic drugs (DMARDs) and/or biologics.
A total of 505 patients were randomized 1:1:1 to placebo (n=169), apremilast 20mg twice daily (20mg; n=169), or apremilast 30mg twice daily (30mg; n=167), stratified by baseline DMARD use and body surface area (BSA) ≥3%.
At Week 16, the primary endpoint, patients with <20% reduction from baseline in swollen/tender joint counts qualified for protocol-defined “early escape”: those on placebo were re-randomized to apremilast 20mg or 30mg, while those on apremilast remained on their initial dose.
At Week 24, all patients remaining in the placebo arm were re-randomized to apremilast 20mg or 30mg through Week 52. Patients taking concurrent DMARDs—eg, methotrexate, sulfasalazine, leflunomide, or a combination—were allowed to continue stable doses.
At Week 16, significantly more patients in the apremilast 20mg (29.4%; P=0.0235) and 30mg arms (42.8%; P<0.0001) achieved an ACR20 response vs. placebo (18.9%). For patients originally randomized to apremilast who completed 52 weeks of the study, improvements were maintained or increased for multiple endpoints, including an ACR20 response of 56.0% (20mg) and 63.0% (30mg), a HAQ-DI mean change from baseline (SD) of -0.332 (0.505) for apremilast 20mg and -0.350 (0.505) for 30mg, and meeting the MCIDs of 0.13 and 0.30.
In patients with baseline BSA ≥3%, PASI-75 was achieved by 28.6% (20mg) and 39.1% (30mg) and Psoriasis Area Severity Index-50 was achieved by 49.2% (20mg) and 54.7% (30mg). The magnitude of responses was higher for apremilast 30mg than 20mg.
Patients randomized to apremilast at Weeks 16 or 24 demonstrated results consistent with those originally randomized to apremilast. Dr. Edwards noted, “Durable improvement of response was observed across all efficacy parameters through Week 52.”
Apremilast was generally well tolerated. Through Week 52, adverse events (AEs) that occurred in ≥5% of all patients were diarrhea, nausea, headache, upper respiratory tract infection, nasopharyngitis, and vomiting. “The majority of AEs were mild/moderate and predominantly did not lead to discontinuation,” he stated.
After the first week of dosing, gastrointestinal AEs occurred at a reduced incidence rate. Serious AEs occurred in 5.4% (20mg) and 4.1% (30mg) of patients, respectively. No new safety signals were identified and the incidence of patients experiencing any AE was comparable over 0–24 and 0–52 weeks.
“No imbalance in the exposure-adjusted incidence rates of severe AEs, serious AEs[DAH1] , major adverse cardiac events, serious infections including systemic opportunistic infection, or malignancies between apremilast and placebo was observed,” they noted. No cases of new or reactivated tuberculosis were reported in the apremilast treatment groups; however, per the protocol, tuberculosis screening was not required.