The efficacy and safety of apremilast, etanercept and placebo in patients with moderate-to-severe plaque psoriasis: 52-week results from a phase IIIb, randomized, placebo-controlled trial (LIBERATE)

Abstract

Background: Apremilast, an oral, small-molecule phosphodiesterase 4 inhibitor, has demonstrated efficacy in patients with moderate-to-severe psoriasis.

Objective: Evaluate efficacy and safety of apremilast vs. placebo in biologic-naive patients with moderate-to-severe plaque psoriasis and safety of switching from etanercept to apremilast in a phase IIIb, randomized, double-blind, placebo-controlled study (NCT01690299).

Methods: Two hundred and fifty patients were randomized to placebo (n = 84), apremilast 30 mg BID (n = 83) or etanercept 50 mg QW (n = 83) through Week 16; thereafter, all patients continued or switched to apremilast through Week 104. The primary efficacy endpoint was achievement of PASI-75 at Week 16 with apremilast vs. placebo. Secondary endpoints included achievement of PASI-75 at Week 16 with etanercept vs. placebo and improvements in other clinical endpoints vs. placebo at Week 16. Outcomes were assessed through Week 52. This study was not designed for apremilast vs. etanercept comparisons.

Results: At Week 16, PASI-75 achievement was greater with apremilast (39.8%) vs. placebo (11.9%; P < 0.0001); 48.2% of patients achieved PASI-75 with etanercept (P < 0.0001 vs. placebo). PASI-75 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 observed through Week 52 with apremilast.

Conclusion: Apremilast demonstrated significant efficacy vs. placebo at Week 16 in biologic-naive patients with psoriasis, which was sustained over 52 weeks, and demonstrated safety 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.

Figure 1

LIBERATE Study Design. *Starting at Week 32, all non‐responders (<PASI‐50) had the option of adding topical therapies and/or ultraviolet B phototherapy (excluding oral psoralen combined with ultraviolet A) to their treatment regimen. Two patients in each group received topical therapy and/or phototherapy. PASI‐50, 50% or greater reduction from baseline in Psoriasis Area and Severity Index score.

Figure 2

Patient Disposition.

Figure 3

PASI‐75 Response at Week 16 (LOCF) and Week 52 (EOP). *P < 0.0001 vs. placebo. The vertical lines indicate two‐sided 95% CIs. CI, confidence interval; EOP, end of phase; LOCF, last observation carried forward; for the apremilast‐extension phase, this includes the last observation in the phase, between Week 16 and Week 52; n/m, number of responders/number of patients with sufficient data for evaluation; PASI‐75, 75% or greater reduction from baseline in Psoriasis Area and Severity Index score.

Figure 4

Percentage of Patients Achieving a DLQI score of 0 or 1 at Week 16 and Week 52. Based on last‐observation‐carried‐forward analysis for Weeks 16 and 52. DLQI, Dermatology Life Quality Index.

Figure 5

(a) Mean Change in DLQI Score. Data represent the mITT population, as observed at each time point. The vertical lines indicate two‐sided 95% CIs. CI, confidence interval; DLQI, Dermatology Life Quality Index. (b) Mean Change in Pruritus VAS Score. *Mean pruritus VAS scores (0–100 mm, where 0 = no itch at all, 100 = worst itch imaginable) were 62.5 mm (placebo), 62.6 mm (apremilast) and 57.2 mm (etanercept) at baseline. Data represent the mITT population, as observed at each time point. The vertical lines indicate two‐sided 95% CIs. VAS, visual analogue scale.