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

BackgroundApremilast, an oral, small‐molecule phosphodiesterase 4 inhibitor, has demonstrated efficacy in patients with moderate‐to‐severe psoriasis.ObjectiveEvaluate 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).MethodsTwo 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.ResultsAt 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.ConclusionApremilast 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.

Safety and efficacy of apremilast through 104 weeks in patients with moderate to severe psoriasis who continued on apremilast or switched from etanercept treatment: findings from the LIBERATE study

“…In patients who continued or were switched from placebo or etanercept to apremilast during the apremilast‐extension phase, PASI‐75 response rate was maintained across treatment groups at Week 52 (range, 52.7%–57.0%)1 and Week 104 (45.9%–51.9%; Table 1; Fig. 1) and was similar between treatment groups.…”

“…At Week 16, mean percentage improvement in PASI score was significantly greater with apremilast compared with placebo ( P < 0.0001). Mean percentage improvement in PASI score was maintained across treatment groups at Week 52 (range, 66.2%–75.1%)1 and continued through Week 104 (63.3%–70.1%; Table 1). Likewise, achievement of sPGA response was significantly greater with apremilast vs. placebo at Week 16 (21.7% vs. 3.6%, P = 0.0005)1; achievement was 24.3%–35.6% across treatment groups at Week 521 and 18.9%–27.4% at Week 104 (Table 1).…”

“…2a and 2b). Improvements were maintained at Week 521 and Week 104 in patients who continued or were switched to apremilast during the apremilast‐extension phase. Mean change from baseline in pruritus VAS score across treatment groups was −31.7 to −35.9 mm at Week 521 and −24.4 to −32.3 mm at Week 104 (Table 1).…”

“…The most common reasons for withdrawal from the apremilast‐extension phase were lack of efficacy ( n = 27, 11.9%), lost to follow‐up ( n = 25, 11.0%) and withdrawal by patient ( n = 24, 10.6%). Baseline characteristics were balanced between groups 1. Mean psoriasis duration was 18.2 years, and mean PASI score was 19.6 1…”

“…LIBERATE (NCT01690299), a global phase 3b study in biologic‐naive patients with moderate to severe plaque psoriasis, demonstrated that significantly more patients receiving apremilast for 16 weeks achieved PASI‐75 (≥75% reduction from baseline in Psoriasis Area and Severity Index [PASI]) vs. placebo 1. A post hoc analysis found no significant difference in response rates among patients given apremilast vs. etanercept, an anti‐tumour necrosis factor‐α biologic agent 1…”