Background/Purpose: Psoriasis is a chronic systemic inflammatory disease often treated with conventional systemic and biologic drugs that may variously be ineffective, be inaccessible, or pose significant safety/tolerability risks. The phase 3b LIBERATE (Evaluation in a Placebo-Controlled Study of Oral Apremilast and Etanercept in Plaque Psoriasis) study (NCT01690299) evaluated the efficacy/safety of apremilast (APR) or etanercept (ETN) vs. placebo (PBO) in biologic-naive patients with moderate to severe plaque psoriasis.

Methods: In the double-blind, double-dummy study, patients were randomized (1:1:1) to PBO, APR 30 mg BID, or ETN 50 mg QW through Week 16; thereafter, all patients switched to or continued APR (PBO/APR, ETN/APR, APR/APR). The primary endpoint was achievement of a ≥75% reduction from baseline Psoriasis Area and Severity Index score (PASI-75) at Week 16 with APR vs. PBO; secondary endpoint was PASI-75 achievement at Week 16 with ETN vs. PBO. Additional physician global assessments (PGA) of disease activity were conducted using the static (sPGA), lattice system (LS-PGA), and scalp (ScPGA) instruments; nail disease was evaluated using the Nail Psoriasis Severity Index (NAPSI). Responses were assessed at Weeks 16 and 52 using the last-observation-carried-forward (LOCF) methodology.

Results: 250 patients received ≥1 dose of study drug, had baseline PASI and ≥1 post-treatment PASI evaluations, and were included in the analysis set (PBO n=84; APR n=83; ETN n=83). At baseline, 66.4% (n=166; PBO n=58; APR n=54; ETN n=54) of patients had an ScPGA score ≥3 (moderate to very severe) and 59.2% (n=148; PBO n=46; APR n=52; ETN n=50) had a NAPSI score ≥1. At Week 16, PASI-75 achievement was significantly greater (P<0.0001) with APR (39.8%) or ETN (48.2%) vs. PBO (11.9%). This study was not designed/powered for APR vs. ETN comparisons; Week 16 PASI-75 achievement did not differ significantly between APR and ETN (P=0.2565, post hoc). At Week 16, APR and ETN produced significantly greater achievement of 0/1 ratings (clear/almost clear) vs. PBO in sPGA, LS-PGA, and ScPGA (clear/minimal) (Table). Improvements in nail psoriasis were also achieved with APR and ETN at Week 16 (Table). At Week 52, PASI-75 response was sustained in APR/APR (50.6%) and ETN/APR (55.4%) patients; 46.4% of PBO/APR patients had a PASI-75 response (Table). sPGA, LS-PGA, and ScPGA responses achieved at Week 16 were generally sustained through Week 52 with APR (Table). Continued APR treatment over 52 weeks resulted in further improvements in nail psoriasis (Table). Overall, adverse events were comparable among the 3 treatment arms. Adverse events with APR and ETN were consistent with their known safety profiles.

Conclusion: APR demonstrated significant efficacy vs. PBO at Week 16; with continued APR treatment, therapeutic responses were generally sustained at Week 52. Efficacy was maintained in ETN patients who switched to APR.