Apremilast Safe, Effective at 3 Years in Psoriatic Arthritis
SAN FRANCISCO, CA—Longer-term efficacy and safety data from the Phase 3 PALACE 1 study have confirmed that apremilast at 20mg and 30mg twice-daily doses continues to demonstrate "sustained and clinically meaningful improvements" in psoriatic arthritis (PsA) signs and symptoms at 3 years in patients who remained on the treatment, investigators reported at the 2015 ACR/ARHP Annual Meeting.
This included improvements in physical function and associated psoriasis, stated Arthur Kavanaugh, MD, of the University of California, San Diego School of Medicine in La Jolla, CA.
"Apremilast continued to demonstrate an acceptable safety profile and was generally well-tolerated," Dr. Kavanaugh reported.
The trial randomly assigned patents with active psoriatic arthritis despite prior conventional disease-modifying antirheumatic drugs (DMARDs) and/or biologics to receive the oral phosphodiesterase 4 inhibitor apremilast at doses of 30mg twice daily or 20mg twice daily, or placebo, stratified by baseline DMARD use (yes/no).
“The placebo-controlled phase continued to Week 24, with an early escape option at Week 16,” Dr. Kavanaugh noted. At Week 24, all remaining placebo patients were re-randomized to apremilast 30mg or 20mg. Double-blind treatment with apremilast continued to Week 52, and patients could continue the agent 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, he said.
Results from the open-label extension showed that 504 patients received at least one dose of study medication: apremilast 30mg (n=168), apremilast 20mg (n=168), or placebo (n=168).
In an “as observed” analysis, 53.2% of patients in the apremilast 30mg dose group and 59.6% of those in the 20mg dose group achieved a modified ACR20 response at Week 52, regardless of whether the agent was initiated at Week 0, 16, or 24. A total of 65.3% of patients in the apremilast 30mg arm and 60.9% in the apremilast 20mg arm showed these responses at Week 104.
Of the 284 patients entering Year 3 of therapy, 92% (260 patients) completed the Week 156 visit, representing 52% of patients randomly assigned at baseline, Dr. Kavanaugh reported.
“Patients receiving apremilast at Week 156 demonstrated sustained improvements, as shown by ACR20/ACR50/ACR70 response rates modified for psoriatic arthritis 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,” Dr. Kavanaugh reported.
With up to 3 years of treatment with apremilast, no new safety concerns were identified. From Year 2 to the end of Year 3, upper respiratory tract infection was the only adverse event that occurred in 5% or more of patients, Dr. Kavanaugh reported. "Diarrhea (2.1%) and nausea (2.1%) occurred at low rates from Year 2 through Year 3, he noted.
Serious adverse events occurred in 6.9% of patients in the apremilast 30mg arm and 6.4% in the apremilast 20mg arm, he reported.