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

Abstract

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

Objective: To evaluate long-term efficacy and safety of apremilast in biologic-naive patients with moderate to severe plaque psoriasis and safety of switching from etanercept to apremilast in the phase 3b LIBERATE trial.

Methods: Two hundred fifty patients were randomized to placebo, apremilast 30 mg BID or etanercept 50 mg QW through Week 16; thereafter, all patients continued or switched to apremilast through Week 104 (extension phase). Skin, scalp and nail involvement at Weeks 16, 52 and 104 were assessed using the Psoriasis Area and Severity Index (PASI; 0-72), Scalp Physician Global Assessment (ScPGA; 0-5) and Nail Psoriasis Severity Index (NAPSI; 0-8); patient-reported outcomes (PROs) were assessed using the Dermatology Life Quality Index (DLQI; 0-32) and pruritus visual analog scale (VAS; 0-100 mm).

Results: The apremilast-extension phase (Weeks 16-104) included 226 patients in the placebo/apremilast (n = 73), apremilast/apremilast (n = 74) and etanercept/apremilast (n = 79) groups, and at Week 104, 50.7%, 45.9% and 51.9% of these patients, respectively, maintained ≥75% reduction from baseline in PASI score (based on last-observation-carried-forward analysis). Across treatment groups, ScPGA 0 (clear) or 1 (minimal) was achieved by 50.0%-59.2% of patients; NAPSI mean change from baseline was -48.1% to -51.1%; DLQI score ≤5 was achieved by 66.0%-72.5% of patients; and pruritus VAS mean change from baseline was -24.4 to -32.3. AEs in ≥5% of patients (diarrhoea, nausea, nasopharyngitis, upper respiratory tract infection and headache) did not increase with prolonged apremilast exposure.

Conclusions: Apremilast demonstrated significant and sustained improvements in skin, scalp, nails and PROs (pruritus and quality of life) over 104 weeks in patients with moderate to severe plaque psoriasis. Safety was consistent with the known safety profile of apremilast.

Figure 1

PASI‐75 response over 104 weeks with apremilast treatment (LOCF). *P < 0.0001, apremilast and etanercept vs. placebo. The vertical lines indicate two‐sided 95% confidence intervals. Missing values were imputed using LOCF methodology. n/m, number of patients with PASI‐75 response/number of patients included in the LOCF analysis at the time point (mITT population for Week 16 [patients who entered and were treated in the apremilast‐extension phase for Weeks 52 and 104]). Numbers of patients in each group with an observation at each time point were: Week 16: placebo n = 73, apremilast n = 74, etanercept n = 81; Weeks 52 and 104 (respectively): placebo/apremilast n = 61 and n = 49, apremilast/apremilast n = 57 and n = 42, etanercept/apremilast n = 67 and n = 52. LOCF, last observation carried forward; mITT, modified intent to treat; PASI, Psoriasis Area and Severity Index; PASI‐75, ≥75% reduction from baseline in PASI score.

Figure 2

Improvement in scalp (a) and nail (b) psoriasis and quality of life (c) over 104 weeks with apremilast treatment. *P = 0.0083 vs. placebo. ^† P = 0.0458 vs. placebo. ^& P = 0.0024 vs. placebo. n/m, number of responders/number of patients with data at time of observation. Week 16 group comparisons based on Cochran–Mantel–Haenszel test stratified by baseline body mass index (<30 kg/m² and ≥30 kg/m²). Missing values for improvements in scalp and nail psoriasis were imputed using LOCF methodology. The vertical lines indicate two‐sided 95% confidence intervals. ScPGA response (0 [clear] or 1 [minimal]) examined among patients with ScPGA ≥3 (moderate or greater) at baseline; NAPSI examined among patients with NAPSI ≥1 at baseline; DLQI ≤5 examined among all patients who had data at time of observation (i.e. completers, without imputation; both P=NS vs. placebo at Week 16). DLQI, Dermatology Life Quality Index; LOCF, last observation carried forward; mITT, modified intent to treat; NAPSI, Nail Psoriasis Severity Index; ScPGA, Scalp Physician Global Assessment.