Background Many patients (pts) with chronic plaque psoriasis exhibit nail and scalp involvement that can markedly affect quality of life and be difficult to treat.
Objectives The phase 3b LIBERATE (Evaluation in a Placebo-Controlled Study of Oral Apremilast and Etanercept in Plaque Psoriasis) study (NCT01690299) evaluated the efficacy and safety of apremilast or etanercept vs. placebo in biologic-naive pts with moderate to severe plaque psoriasis. Efficacy assessments included effects on preexisting nail and scalp disease and skin lesions.
Methods In this double-blind, double-dummy study, pts were randomized (1:1:1) to placebo (PBO), apremilast 30 mg BID (APR), or etanercept 50 mg QW (ETN) through Week 16; thereafter, all pts switched to or continued APR (PBO/APR, ETN/APR, APR/APR) through Week 104. The primary end point was achievement of a ≥75% reduction from baseline in Psoriasis Area and Severity Index (PASI) score (PASI-75) at Week 16 with APR vs. PBO; the secondary end point was PASI-75 achievement at Week 16 with ETN vs. PBO. Physician assessments were also conducted for overall disease activity (static Physician's Global Assessment [sPGA]); scalp disease activity (Scalp Physician Global Assessment [ScPGA], limited to patients with score ≥3 at baseline, indicating moderate to very severe scalp disease); and nail disease (Nail Psoriasis Severity Index [NAPSI], limited to patients with active disease [NAPSI ≥1] in the target nail at baseline). Responses were assessed at Week 104 using the last-observation-carried-forward (LOCF) methodology.
Results The APR extension phase (Weeks 16 to 104) included 226 pts (PBO/APR n=73; APR/APR n=74; ETN/APR n=79). At Week 16, PASI-75 scores vs. PBO were significant for both APR and ETN; long-term treatment with APR maintained both PASI-75 and sPGA 0 or 1 response levels (Table). Improvements were seen in nail and scalp disease at Week 16, and responses continued to improve with APR treatment over 104 weeks and in pts who switched from ETN to APR (Table). ScPGA 0 or 1 was achieved by 50.0% to 59.2% of pts across treatment arms, and mean percent improvement from baseline NAPSI score ranged from −48.1% to −51.1% (Table); the proportion of pts achieving NAPSI-50 response ranged from 48.6% to 65.2%. Adverse events (AEs) occurring in ≥5% of pts during Weeks 0 to 16 were diarrhea, nausea, nasopharyngitis, upper respiratory tract infection, and headache; long-term assessment by exposure-adjusted incidence rates (EAIR)/100 pt-yrs showed no increase with longer-term APR exposure. No increase in EAIR/100 pt-yrs of serious AEs occurred during the APR extension phase (3.45 to 5.49, across groups) vs. Weeks 0 to 16 (PBO 0.0; ETN 7.91; APR 12.57). Changes in laboratory parameters were infrequent and transient; EAIR/100 pt-yrs remained low across groups through 104 weeks.
Conclusions APR demonstrated efficacy through Week 104 in pts who continued APR and pts who switched from PBO or ETN to APR at Week 16. The AE profile remained consistent with prolonged APR exposure, and no new safety or tolerability issues were observed through Week 104 in pts with moderate to severe plaque psoriasis.
Disclosure of Interest K. Reich Consultant for: AbbVie, Amgen, Biogen, Boehringer Ingelheim, Celgene Corporation, Centocor, Covagen, Eli Lilly, Forward Pharma, GlaxoSmithKline, Janssen-Cilag, LEO Pharma, Medac, Merck Sharp & Dohme, Novartis, Ocean Pharma, Pfizer (Wyeth), Regeneron, Takeda, UCB Pharma, and XenoPort, Speakers bureau: AbbVie, Amgen, Biogen, Boehringer Ingelheim, Celgene Corporation, Centocor, Covagen, Eli Lilly, Forward Pharma, GlaxoSmithKline, Janssen-Cilag, LEO Pharma, Medac, Merck Sharp & Dohme, Novartis, Ocean Pharma, Pfizer (Wyeth), Regeneron, Takeda, UCB Pharma, and XenoPort, M. Goodfield: None declared, L. Green Consultant for: AbbVie, Amgen, Celgene Corporation, LEO Pharma, Novartis, Pfizer, and Valeant, Speakers bureau: AbbVie, Amgen, Celgene Corporation, LEO Pharma, Novartis, Pfizer, and Valeant, K. Nograles Employee of: Celgene Corporation, R. Chen Employee of: Celgene Corporation, E. Levi Employee of: Celgene Corporation, R. Langley Speakers bureau: AbbVie, Amgen, Celgene Corporation, Eli Lilly, LEO Pharma, Merck, Novartis, and Pfizer
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