Efficacy, tolerability, and pharmacodynamics of apremilast in recalcitrant plaque psoriasis: A phase II open-label study

Journal of Drugs in Dermatology

Volumn 12, Issue 8, 2013, Pages 888-897

  Gottlieb, Alice B ^a   Matheson, Robert T ^b   Menter, Alan ^c   Leonardi, Craig L ^d   Day, Robert M ^e   Hu, ChiaChi ^e   Schafer, Peter H ^e   Krueger, James G ^f  

^a TUFTS MEDICAL CENTER   (United States)

^b OREGON MEDICAL RESEARCH CENTER   (United States)

^c BAYLOR UNIVERSITY MEDICAL CENTER   (United States)

^d SAINT LOUIS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^e CELGENE CORPORATION   (United States)

^f ROCKEFELLER UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

APREMILAST; INTERLEUKIN 23; INTERLEUKIN 7;

ADULT; ARTICLE; BODY SURFACE; CLINICAL ARTICLE; CLINICAL EVALUATION; CONTROLLED STUDY; COUGHING; CYST; DELUSIONAL PARASITOSIS; DIARRHEA; DRUG DOSE REDUCTION; DRUG DOSE TITRATION; DRUG EFFICACY; DRUG INDUCED HEADACHE; DRUG SAFETY; DRUG TOLERABILITY; DRUG WITHDRAWAL; DYSPEPSIA; EPISTAXIS; FATIGUE; FEMALE; FLATULENCE; FOLLOW UP; GASTROINTESTINAL MOTILITY DISORDER; HUMAN; HUMAN TISSUE; IMMUNOHISTOCHEMISTRY; LIMB PAIN; LOWER RESPIRATORY TRACT INFECTION; MALE; MIGRAINE; MULTICENTER STUDY; NAUSEA; OPEN STUDY; PHASE 2 CLINICAL TRIAL; PRURITUS; PSORIASIS AREA AND SEVERITY INDEX; PSORIASIS VULGARIS; PSORIATIC ARTHRITIS; PUSTULOSIS PALMOPLANTARIS; RHINOPHARYNGITIS; SINUS CONGESTION; SKIN BIOPSY; SKINFOLD THICKNESS; TH17 CELL; TREATMENT DURATION;

ADULT; ANTI-INFLAMMATORY AGENTS, NON-STEROIDAL; FEMALE; FOLLOW-UP STUDIES; HUMANS; INFLAMMATION; LEUKOCYTES; MALE; MIDDLE AGED; PHOSPHODIESTERASE 4 INHIBITORS; PSORIASIS; SEVERITY OF ILLNESS INDEX; THALIDOMIDE; TREATMENT OUTCOME;

EID: 84882372494     PISSN: 15459616     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Article

References (27)

1. Augustin M, Reich K, Glaeske G, Schaefer I, Radtke M. Co-morbidity and age-related prevalence of psoriasis: analysis of health insurance data in Germany. Acta Derm Venereol. 2010;90:147-151.
2. Menter A, Gottlieb A, Feldman SR, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 1. Overview of psoriasis and guidelines of care for the treatment of psoriasis with biologics. J Am Acad Dermatol. 2008;58:826-850.
3. Saurat JH, Guerin A, Yu AP, et al. High prevalence of potential drug-drug interactions for psoriasis patients prescribed methotrexate or cyclosporine for psoriasis: associated clinical and economic outcomes in real-world practice. Dermatology. 2010;220:128-137.
4. Ravindran V, Scott DL, Choy EH. A systematic review and meta-analysis of efficacy and toxicity of disease modifying anti-rheumatic drugs and biological agents for psoriatic arthritis. Ann Rheum Dis. 2008;67:855-859.
5. Brunasso AM, Puntoni M, Salvini C, et al. Tolerability and safety of biological therapies for psoriasis in daily clinical practice: a study of 103 Italian patients. Acta Derm Venereol. 2011;91:44-49.
6. Serezani CH, Ballinger MN, Aronoff DM, Peters-Golden M. Cyclic AMP: master regulator of innate immune cell function. Am J Respir Cell Mol Biol. 2008;39:127-132.
7. Tasken K, Aandahl EM. Localized effects of cAMP mediated by distinct routes of protein kinase A. Physiol Rev. 2004;84:137-167.
8. Schafer P. Apremilast mechanism of action and application to psoriasis and psoriatic arthritis. Biochem Pharmacol. 2012;83:1583-1590.
9. Heystek HC, Thierry A-C, Soulard P, Moulon C. Phosphodiesterase 4 inhibitors reduce human dendritic cell inflammatory cytokine production and Th1-polarizing capacity. Int Immunol. 2003;15:827-835.
10. Schafer PH, Parton A, Gandhi AK, et al. Apremilast, a cAMP phosphodiesterase-4 inhibitor, demonstrates anti-inflammatory activity in vitro and in a model of psoriasis. Br J Pharmacol. 2010;159:842-855.
11. Claveau D, Chen SL, O'Keefe S, et al. Preferential inhibition of T helper 1, but not T helper 2, cytokines in vitro by L-826, 141 [4-[2-(3,4- Bisdifluromethoxyphenyl)-2-[4-(1,1,1,3,3,3-hexafluoro-2-hydroxypropan-2-yl) -phenyl]-ethyl]3-methylpyridine-1-oxide], a potent and selective phosphodiesterase 4 inhibitor. J Pharmacol Exp Ther. 2004;310:752-760.
12. Papp K, Cather J, Rosoph L, et al. The efficacy of apremilast, a phosphodiesterase-4 inhibitor, in the treatment of moderate to severe psoriasis: results of a phase 2 randomised study. Lancet. 2012;380:738-746.
13. Schett G, Wollenhaupt J, Papp K, et al. Oral apremilast in the treatment of active psoriatic arthritis: results of a multicenter, randomized, double-blind, placebo-controlled study. Arthritis Rheum. 2012;64:3156-3167.
14. Kavanaugh A. Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis: results of a phase 3, randomized, controlled trial [oral presentation]. Presented at: the 2012 ACR/ARHP Annual Meeting; November 9-14, 2012; Washington, DC.
15. Gottlieb AB, Strober B, Krueger JG, et al. An open-label, single-arm pilot study in patients with severe plaque-type psoriasis treated with an oral antiinflammatory agent, apremilast. Curr Med Res Opin. 2008;24:1529-1538.
16. Papp KA, Kaufmann R, Thaci D, Hu C, Sutherland D, Rohane P. Efficacy and safety of apremilast in subjects with moderate to severe plaque psoriasis: results from a phase II, multicenter, randomized, double-blind, placebo-controlled, parallel-group, dose-comparison study. J Eur Acad Dermatol Venereol. 2012.
17. Schafer PH. Targeting PDE4 with apremilast, an orally available specific PDE4 inhibitor, in clinical trials for the treatment of psoriasis and arthritis. Presented at: 8th International Congress on Autoimmunity; May 9-13, 2012; Granada, Spain.
18. Capone L, Rogovitz A, Gandhi AK, Schafer PH. Anti-inflammatory activity of apremilast against T cells, chondrocytes, and rheumatoid arthritis synovial fibroblasts in vitro [abstract 1844]. Presented at: Annual Scientific Meeting of the American College of Rheumatology; November 4-9, 2011; Chicago, IL.
19. Haider AS, Lowes MA, Suarez-Farinas M, et al. Identification of cellular pathways of "type 1," Th17 T cells, and TNF- and inducible nitric oxide synthaseproducing dendritic cells in autoimmune inflammation through pharmacogenomic study of cyclosporine A in psoriasis. J Immunol. 2008;180:1913-1920.
20. Wada Y, Cardinale I, Khatcherian A, et al. Apilimod inhibits the production of IL-12 and IL-23 and reduces dendritic cell infiltration in psoriasis. PLoS One. 2012;7:e35069.
21. Zaba LC, Cardinale I, Gilleaudeau P, et al. Amelioration of epidermal hyperplasia by TNF inhibition is associated with reduced Th17 responses. J Exp Med. 2007;204:3183-3194.
22. Krueger JG, Fretzin S, Suarez-Farinas M, et al. IL-17A is essential for cell activation and inflammatory gene circuits in subjects with psoriasis. J Allergy Clin Immunol. 2012;130:145-154.
23. Leonardi C, Matheson R, Zachariae C, et al. Anti-interleukin-17 monoclonal antibody ixekizumab in chronic plaque psoriasis. N Engl J Med. 2012;366:1190-1199.
24. Papp KA, Leonardi C, Menter A, et al. Brodalumab, an anti-interleukin-17- receptor antibody for psoriasis. N Engl J Med. 2012;366:1181-1189.
25. Abrahamsen H, Baillie G, Ngai J, et al. TCR- and CD28-mediated recruitment of phosphodiesterase 4 to lipid rafts potentiates TCR signaling. J Immunol. 2004;173:4847-4858.
26. Ghoreschi K, Jesson MI, Li X, et al. Modulation of innate and adaptive immune responses by tofacitinib (CP-690, 550). J Immunol. 2011;186:4234-4243.
27. Kovarik JM, Stitah S, Slade A, et al. Sotrastaurin and tacrolimus coadministration: effects on pharmacokinetics and biomarker responses. J Clin Pharmacol. 2010;50:1260-1266.