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) - PubMed (original) (raw)
Clinical Trial
. 2017 Mar;31(3):507-517.
doi: 10.1111/jdv.14015. Epub 2016 Dec 19.
Affiliations
- PMID: 27768242
- PMCID: PMC5363370
- DOI: 10.1111/jdv.14015
Clinical Trial
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)
K Reich et al. J Eur Acad Dermatol Venereol. 2017 Mar.
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.
© 2016 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.
Figures
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%
CI
s.
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%
CI
s.
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%
CI
s.
VAS
, visual analogue scale.
Similar articles
- 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.
Reich K, Gooderham M, Bewley A, Green L, Soung J, Petric R, Marcsisin J, Cirulli J, Chen R, Piguet V. Reich K, et al. J Eur Acad Dermatol Venereol. 2018 Mar;32(3):397-402. doi: 10.1111/jdv.14738. Epub 2018 Jan 29. J Eur Acad Dermatol Venereol. 2018. PMID: 29220542 Free PMC article. Clinical Trial. - Apremilast, an oral phosphodiesterase 4 inhibitor, in the treatment of Japanese patients with moderate to severe plaque psoriasis: Efficacy, safety and tolerability results from a phase 2b randomized controlled trial.
Ohtsuki M, Okubo Y, Komine M, Imafuku S, Day RM, Chen P, Petric R, Maroli A, Nemoto O. Ohtsuki M, et al. J Dermatol. 2017 Aug;44(8):873-884. doi: 10.1111/1346-8138.13829. Epub 2017 Apr 9. J Dermatol. 2017. PMID: 28391657 Free PMC article. Clinical Trial. - Efficacy and Safety of Apremilast in Systemic- and Biologic-Naive Patients With Moderate Plaque Psoriasis: 52-Week Results of UNVEIL.
Stein Gold L, Bagel J, Lebwohl M, Jackson JM, Chen R, Goncalves J, Levi E, Duffin KC. Stein Gold L, et al. J Drugs Dermatol. 2018 Feb 1;17(2):221-228. J Drugs Dermatol. 2018. PMID: 29462231 Clinical Trial. - Apremilast for psoriasis treatment.
Carrascosa JM, Del-Alcazar E. Carrascosa JM, et al. G Ital Dermatol Venereol. 2020 Aug;155(4):421-433. doi: 10.23736/S0392-0488.20.06684-5. Epub 2020 Jun 15. G Ital Dermatol Venereol. 2020. PMID: 32545946 Review. - Comparative efficacy and incremental cost per responder of methotrexate versus apremilast for methotrexate-naïve patients with psoriasis.
Armstrong AW, Betts KA, Sundaram M, Thomason D, Signorovitch JE. Armstrong AW, et al. J Am Acad Dermatol. 2016 Oct;75(4):740-746. doi: 10.1016/j.jaad.2016.05.040. Epub 2016 Jul 28. J Am Acad Dermatol. 2016. PMID: 27476973 Review.
Cited by
- Interleukin-receptor antagonist and tumour necrosis factor inhibitors for the primary and secondary prevention of atherosclerotic cardiovascular diseases.
Martí-Carvajal AJ, Gemmato-Valecillos MA, Monge Martín D, Dayer M, Alegría-Barrero E, De Sanctis JB, Parise Vasco JM, Riera Lizardo RJ, Nicola S, Martí-Amarista CE, Correa-Pérez A. Martí-Carvajal AJ, et al. Cochrane Database Syst Rev. 2024 Sep 19;9(9):CD014741. doi: 10.1002/14651858.CD014741.pub2. Cochrane Database Syst Rev. 2024. PMID: 39297531 - [Phosphodiesterase 4 inhibitors in dermatology : Role in the treatment of skin diseases].
Schmidt MF, Albuscheit N, Yazdi AS. Schmidt MF, et al. Dermatologie (Heidelb). 2024 Oct;75(10):791-797. doi: 10.1007/s00105-024-05407-7. Epub 2024 Aug 30. Dermatologie (Heidelb). 2024. PMID: 39212723 Review. German. - Functional Genomics and Insights into the Pathogenesis and Treatment of Psoriasis.
Shellard EM, Rane SS, Eyre S, Warren RB. Shellard EM, et al. Biomolecules. 2024 May 3;14(5):548. doi: 10.3390/biom14050548. Biomolecules. 2024. PMID: 38785955 Free PMC article. Review. - Effectiveness of sequential lines of biologic and targeted small molecule drugs in psoriasis: A systematic review and meta-analysis.
Gollins CE, Vincent R, Fahy C, McHugh N, Tillett W. Gollins CE, et al. Skin Health Dis. 2024 Feb 29;4(2):e350. doi: 10.1002/ski2.350. eCollection 2024 Apr. Skin Health Dis. 2024. PMID: 38577060 Free PMC article. - Effects on Lipid Profile after One Year of Apremilast Therapy in Patients with Psoriasis: A Monocentric Experience.
Guerra P, Di Cesare A, Rosi E, Scandagli I, Silvi G, Nunziati G, Prignano F. Guerra P, et al. Life (Basel). 2024 Mar 16;14(3):395. doi: 10.3390/life14030395. Life (Basel). 2024. PMID: 38541719 Free PMC article.
References
- Reich K. The concept of psoriasis as a systemic inflammation: implications for disease management. J Eur Acad Dermatol Venereol 2012; 26(Suppl 2): 3–11. - PubMed
- Coimbra S, Figueiredo A, Castro E, Rocha‐Pereira P, Santos‐Silva A. The roles of cells and cytokines in the pathogenesis of psoriasis. Int J Dermatol 2012; 51: 389–398. - PubMed
- Taheri A, Sandoval LF, Moradi Tuchay S, Alinia H, Mansoori P, Feldman SR. Emerging treatment options for psoriasis. Psoriasis Targets Ther 2014; 4: 27–35.
- Schafer P. Apremilast mechanism of action and application to psoriasis and psoriatic arthritis. Biochem Pharmacol 2012; 83: 1583–1590. - PubMed
- Schafer PH, Parton A, Capone L et al Apremilast is a selective PDE4 inhibitor with regulatory effects on innate immunity. Cell Signal 2014; 26: 2016–2029. - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical