placebo (11. 9%; P <0. 0001); 48. 2% of patients achieved PASI75 with etanercept (P <0. 0001 vs . (39. 8%) vs . placebo (11. 9%; P <0. 0001); 48. 2% of patients achieved PASI75 with etanercept (P <0. 0001 vs . placebo). PASI75 response was maintained in 47. 3% (apremilast/apremilast), 49. 4% (etanercept/apremilast) and 47. 9% (placebo/apremilast) of patients at Week 52. Most common adverse events (5%) with apremilast, including nausea, diarrhoea, upper respiratory tract infection, nasopharyngitis, tension headache and headache, were mild or moderate in severity; diarrhoea and nausea generally resolved in the first month. No new safety or tolerability issues were noticed through Week 52 with apremilast. == Conclusion == Apremilast demonstrated significant efficacy vs . placebo at Week 16 in biologicnaive patients with psoriasis, which was sustained over 52 weeks, and demonstrated security consistent with the known safety profile of apremilast. Switching from etanercept to apremilast did not result in any new or clinically significant safety findings, and efficacy was maintained with apremilast through Week 52. == Introduction == Psoriasis is a chronic, systemic inflammatory disease marked by overproduction of proinflammatory mediators. 1, 2Early treatment with effective brokers that target the pathophysiologic pathways of psoriasis and have improved safety profiles is needed intended for longterm treatment of patients with chronic plaque psoriasis. 3Apremilast, an oral smallmolecule phosphodiesterase 4 (PDE4) inhibitor, works intracellularly to regulate inflammatory mediators, including pathways relevant to the pathogenesis of psoriasis. 4, 5PDE4 inhibition elevates cyclic adenosine monophosphate levels, which downregulates inflammatory responses and upregulates production of antiinflammatory cytokines. 5, 6Apremilast offers demonstrated clinically meaningful improvements in the treatment of psoriatic arthritis in patients with active disease Ramelteon (TAK-375) in the Psoriatic Arthritis Longterm Assessment of Clinical Efficacy (PALACE) phase III clinical trial programme (PALACE 1 [NCT01172938]; PALACE 2 [NCT01212757]; PALACE 3 [NCT01212770]). 7, 8, 9The efficacy Ramelteon (TAK-375) and security of apremilast in patients with moderatetosevere plaque psoriasis who were candidates for phototherapy or systemic therapy have been demonstrated in the global, phase III placebocontrolled Efficacy and Safety Trial Evaluating the Effects of Apremilast in Psoriasis clinical trial programme (ESTEEM 1 [NCT01194219] and ESTEEM 2 [NCT01232283]). 10, 11 Here, we report the findings from a phase IIIb study (Evaluation in a PlaceboControlled Study of Oral Apremilast and Etanercept in Plaque Psoriasis [LIBERATE]) that evaluated apremilast vs . placebo at Week 16 in biologicnaive patients with moderatetosevere plaque psoriasis. The study also included an active control equip that investigated the efficacy of etanercept 50 mg subcutaneous injection Ramelteon (TAK-375) QW vs . placebo at Week 16 and the Ramelteon (TAK-375) family member safety of switching from etanercept to apremilast at Week 16 as compared with uninterrupted apremilast through Week 52. The study was not designed or powered to make direct comparisons between apremilast and etanercept, and comparison of the efficacy and safety from the two active arms was not a prespecified objective from the trial. In contrast to the ESTEEM trials, the current study did not include a randomized withdrawal phase by Psoriasis Area and Severity Index (PASI) response at Week 32, Mouse monoclonal to FMR1 allowing assessment from the efficacy of longterm uninterrupted apremilast treatment through Week 52. Additionally , in the ESTEEM trials, up to onethird of patients had received prior biologic therapy. 10, 11 == Materials and methods == LIBERATE was a global, phase IIIb, multicentre, randomized, doubleblind, placebocontrolled study (NCT01690299). Patients provided written informed consent. The protocol and consent were approved by institutional review boards or ethics committees for all investigational sites. The study was conducted in accordance with the principles of Good Clinical Practice and the Declaration of Helsinki. == Study population == Adult patients aged 18 years were eligible if they had chronic plaque psoriasis intended for 12 months (PASI.