Apremilast and its role in psoriatic arthritis

Psoriatic arthritis (PsA) is a seronegative inflammatory arthritis often observed in patients with skin psoriasis. Treatment of PsA, especially peripheral PsA, has typically relied on disease-modifying anti-rheumatic agents (DMARDs); however, these agents have limited efficacy and considerable associated toxicity. More recently, monoclonal antibodies (biologic agents) have revolutionized management of immune-mediated diseases; however, these therapies carry a high cost and require parenteral administration. Apremilast, a novel oral DMARD, was approved by the European Union for psoriatic arthritis in 2015. Apremilast inhibits the function of phosphodiesterase-4, a regulator of cyclic adenosine monophosphate, leading to a broad inhibition of proinflammatory mediators and subsequent reduction in tumour necrosis factor-alpha (TNF-alpha) response. The PALACE and ACTIVE trials, phase III randomized controlled trials for apremilast, showed that apremilast is effective at improving various clinical and patient-reported outcome measures for psoriatic arthritis in both DMARD-naive and DMARD-experienced PsA patients. Efficacy was limited in patients with previous biologic DMARD failure and the overall efficacy of apremilast appears to be less than biologics agents, though no head-to-head trials exist comparing apremilast to biologic DMARDs. Apremilast is generally well tolerated, with short-lived gastrointestinal side effects being the most commonly reported adverse events. Guidelines suggest a trial of apremilast in patients who have failed traditional oral DMARDs and for whom, biologics are contraindicated. More studies directly comparing apremilast to conventional DMARDs and biologic DMARDs are needed and will be crucial in informing clinical and economic decisions about apremilast role in management of PsA.