• Rheumatology Clinical Trials
• Arthritis

In a late-breaking clinical trial reported by Arthur Kavanaugh, MD, University of California, San Diego, California, USA, apremilast, an oral phosphodiesterase 4 inhibitor, was shown to be safe and effective in treating psoriatic arthritis (PsA) in subjects previously exposed to disease-modifying antirheumatic drugs (DMARDs). Apremilast modulates the production of pro- (tumor necrosis factor [TNF]-α, natural killer [NK] cells, and epidermal keratinocytes) and anti-inflammatory mediators (interleukin [IL]-10), including those implicated in the etiopathogenesis of PsA.

The Efficacy and Safety Study of Apremilast to Treat Active Psoriatic Arthritis [PALACE-1; NCT01172938] was a randomized, placebo-controlled study in subjects with a documented PsA diagnosis for ≥6 months who were previously or currently being treated with DMARDs or biologics. Participants could not have failed >3 DMARDs or >1 TNF inhibitors. Concurrent treatment with stable doses of methotrexate (MTX), sulfasalazine, or leflunomide was allowed. A total of 504 subjects were randomized (1:1:1) to placebo, 20 mg BID apremilast, or 30 mg BID apremilast and stratified by baseline DMARD use. Placebo subjects in whom the tender and swollen joint counts had not improved by at least 20% at Week 16 were re-randomized to apremilast 20 or 30 mg BID. At Week 24, all remaining placebo subjects were re-randomized to apremilast 20 or 30 mg BID.

At baseline, the mean age of the subjects was ∼50 years, mean duration of PsA and psoriasis was ∼7.5 years and 16 years, respectively, and mean 28-joint Disease Activity Score was ∼4.9. Seventy-two percent of patients had prior use of DMARDs (54.2% MTX), 22% had prior use of TNF inhibitors, and 9% had failed treatment with a TNF inhibitor.

The percentage of subjects achieving an American College of Rheumatology 20% improvement criteria (ACR20) response at Week 16 was significantly greater for subjects treated with 20 mg (31%; p<0.02) and 30 mg (41%; p<0.0001) apremilast compared with placebo (19%). Higher ACR responses were seen in subjects receiving apremilast 30 mg plus monotherapy and in biologic-naïve subjects compared with the overall population response. At Week 24, apremilast was associated with significant (p<0.05) differences compared with placebo on the ACR50, ACR70, HAQ-DI, and visual analog scale pain scores, as well as on the DAS28 and European League Against Rheumatism response.

In general, response rates were higher with apremilast 30 mg BID. Apremilast was generally well tolerated. There were no significant differences as to number of adverse events (AEs), serious AEs, or AEs leading to withdrawal between groups; 95% of AEs were mild or moderate in severity. The most common AEs were diarrhea, nausea, headache, and upper respiratory tract infection.

Inhibition of TNF-α and IL production, as well as NK and keratinocyte responses by this phosphodiesterase-4 inhibitor suggests a novel approach to the treatment of psoriasis [Schafer P et al. Br J Pharmacol 2010].

• © 2012 MD Conference Express®