Date: 2015-06-09
Type of information: Presentation of results at a congress
phase: 3
Announcement: presentation of results at the European League Against Rheumatism Annual Congress (EULAR 2015)
Company: Celgene (USA - NJ)
Product: Otezla® (apremilast)
Action
mechanism: phosphodiesterase 4 inhibitor. Apremilast is an oral, small-molecule, selective inhibitor of phosphodiesterase 4 (PDE4) specific for cyclic adenosine monophosphate (cAMP). PDE4 inhibition results in increased intracellular cAMP levels. Otezla® is approved for the treatment of patients with moderate to severe plaque psoriasis who are candidates for phototherapy or systemic therapy and for the treatment of adults with active psoriatic arthritis.
Disease: psoriatic arthritis
Therapeutic area: Autoimmune diseases – Inflammatory diseases - Rheumatic diseases
Country: Australia, Austria, Belgium, Bulgaria, Canada, Czech Republic, Estonia, Finland, France, Germany, Hungary, Italy, Republic of Korea, Lithuania, New Zealand, Poland, Romania, Russian Federation, Slovakia, South Africa, Spain, Switzerland, UK, USA
Trial
details: PALACE 1, 2 and 3 are the pivotal phase III multi-center, double-blind, placebo-controlled, parallel-group studies with two active-treatment groups. Approximately 1,500 patients were randomized 1:1:1 to receive either Otezla® 20 mg twice daily, Otezla® 30 mg twice daily or identically-appearing placebo, for 16 weeks. At week 16, some placebo-treated patients were randomized to one of the two Otezla® groups, while others remained on placebo through week 24. After week 24, patients began a subsequent long term, open-label, active treatment phase. The PALACE 1, 2 and 3 studies included a wide spectrum of patients with active psoriatic arthritis, including those who had been previously treated with oral disease-modifying antirheumatic drugs (DMARDs), and/or biologics, with some patients who had previously failed a tumor necrosis factor (TNF) blocker. The primary endpoint of the PALACE 1, 2 and 3 studies was the modified American College of Rheumatology criteria for 20 percent improvement (ACR20) at week 16. Secondary endpoints included other measures of signs and symptoms of psoriatic arthritis, physical functioning and patient-reported outcomes. PALACE-1 (NCT01172938) PALACE-2 (NCT01212757) PALACE-3 (NCT01212770)
Latest
news: * On June 9, 2015, Celgene announced that the findings from a long-term (104-week) post-hoc analysis of pooled data from the PALACE phase III clinical trial program of Otezla® (apremilast) will be presented at the European League Against Rheumatism (EULAR) Annual Congress in Rome, Italy. Dr. Gladman, the lead investigator of the study, will present the analysis of pooled data from the PALACE 1, 2 and 3 phase III clinical trials in which patients with enthesitis and dactylitis at baseline were allowed to be evaluated for the therapeutic benefit of Otezla® on enthesitis and dactylitis over 104 weeks. In the PALACE trials, patients were randomized to receive either Otezla® 20 mg twice daily, Otezla® 30 mg twice daily or identically appearing placebo for the first 16 weeks. At week 16, some placebo-treated patients were randomized to one of the two v groups, while others remained on placebo through week 24. At week 24, patients either continued on Otezla® or were switched from placebo to Otezla® 20 mg or 30 mg twice daily in a long term, open-label, active treatment phase. Although enthesitis and dactylitis involvement were not required for patients to enter the study, and patients were not stratified according to baseline enthesitis or dactylitis, approximately 63 percent (945/1,493) of patients had pre-existing enthesitis at baseline and approximately 42 percent (633/1,493) of patients had pre-existing dactylitis at baseline. A post-hoc analysis on the effect of Otezla® on enthesitis and dactylitis in patients with pre-existing enthesitis or dactylitis was performed on as-observed pooled data from PALACE 1, 2 and 3. The study abstract states that treatment with Otezla® 30 mg twice daily in patients with pre-existing enthesitis (inflammation at sites where tendons or ligaments insert into bone) or dactylitis (inflammation of an entire digit) — two distinct manifestations of psoriatic arthritis — demonstrated improvements in these symptoms at 52 weeks and that improvements were sustained through week 104. For patients taking Otezla® 30 mg twice daily, the mean Maastricht Ankylosing Spondylitis Enthesitis Score (MASES) was reduced by 43.5 percent at week 52 (n=377) and by 57.5 percent at week 104 (n=302). A score of 0, indicating no pain at any of the sites assessed, was achieved by 37.7 percent of patients at week 52 and 48.7 percent at week 104. Otezla® 30 mg twice daily also resulted in a mean 67.9 percent decrease in dactylitis count at week 52 (n=249) and 80.0 percent decrease at week 104 (n=200). A dactylitis count of 0, indicating no signs of dactylitis, was achieved by 67.5 percent of patients at week 52 and 77.5 percent of patients at week 104. During weeks 0 to 52, adverse events (AEs) occurring in at least five percent of patients treated with Otezla® were diarrhea, nausea, headache, upper respiratory tract infection (URTI) and nasopharyngitis. Rates of URTI, nasopharyngitis, diarrhea, nausea and headache between weeks 52 and 104 were 6.5 percent, 5.8 percent, 2.9 percent, 1.8 percent and 3.0 percent, respectively. No new safety concerns were identified, and no increases were seen in AE incidence or severity with longer exposure.
