THE EFFICACY AND SAFETY OF THE NEW DRUG APREMILAST FOR THE TREATMENT OF PSORIASIS AND PSORIATIC ARTHRITIS
https://doi.org/10.14412/1995-4484-2016-572-577
Abstract
Apremilast (AP) is a new phosphodiesterase 4 inhibitor for the treatment of psoriasis and psoriatic arthritis (PsA). Treatment with AP reduces the level of proinflammatory cytokines and the activity of inflammatory changes.
The positive impact of AP treatment on the course of psoriasis has been proven in a number of clinical trials, for example ESTEEM 1 (Efficacy and Safety Trial Evaluating the Effects of apreMilast in psoriasis), in which the treatment with AP has led to a decrease in PASI scores in patients with moderate and severe psoriasis en plaque: after 16 weeks, a 75% PASI improvement was significantly more common in patients taking AP 30 mg twice daily (33%) than in those who used placebo (PL) (5%) (p = 0.0001). In the PALACE 1 trial, the PsA patients were given AP at a dose of 20 or 10 mg twice daily. At 16 weeks, the patients who used AP at doses 20 and 30 mg twice daily, more frequently showed a 20% improvement according to the American College of Rheumatology (ACR) response criteria (ACR20) than those who received PL (in 30.4, 38.1, and 19% of cases; p = 0.0166 and p = 0.0001, respectively). Following 52 weeks of AP treatment, ACR20 was achieved by 63.0% of the patients who took the drug at 20 mg twice daily, and by 54.6% of those who used 30 mg twice daily. The PALACE 1, PALACE 2, and PALACE 3 trials demonstrated that the most common adverse events (AE) were diarrhea, nausea, headache, upper respiratory tract infections, and nasopharyngitis. Most AE were mild and moderate; and the rate of therapy discontinuation due to AE was low.
These PALACE trials covering 1493 patients have provided evidence for the efficacy and safety of AP in treating moderate PsA activity.About the Authors
Yu. L. Korsakova
V.A. Nasonova Research Institute of Rheumatology
Russian Federation
Russian Federation
Yulia Korsakova.
34A, Kashirskoe Shosse, Moscow 115522
L. N. Denisov
V.A. Nasonova Research Institute of Rheumatology
Russian Federation
Russian Federation
34A, Kashirskoe Shosse, Moscow 115522
References
1. Gladman DD, Antoni C, Mease P, et al. Psoriatic arthritis epidemiology, clinical features, course, and outcome. Ann Rheum Dis. 2005;64(Suppl 2):ii14-7. doi: 10.1136/ard.2004.032482
2. Mease PJ, Gladman D, Kim A, et al. Prevalence of rheumatologist-diagnosed psoriatic arthritis in patients with psoriasis in European/North American dermatology clinics. J Am Acad Dermatol. 2013;69(5):729-35. doi: 10.1016/j.jaad.2013.07.023
3. Taylor W, Gladman D, Helliwell P, et al. Classification criteria for psoriatic arthritis; development of new criteria from a large international study. Arthritis Rheum. 2006;54:2665-73. doi: 10.1002/art.21972
4. Soriano E. The actual role of therapy with traditional diseasemodifying antirheumatic drugs in psoriatic arthritis. J Rheumatol. 2012;89(Suppl):67-70. doi: 10.3899/jrheum.120248
5. Kingsley G, Kowalczyk A, Taylor H, et al. A randomized placebocontrolled trial of methotrexate in psoriatic arthritis. Rheumatology. 2012;51:1368-77. doi: 10.1093/rheumatology/kes001
6. Clegg DO, Reda DJ, Abdellatif M. Comparison of sulphasalazine and placebo for the treatment of axial and peripheral articular manifestation of the seronegative spondyloarthritis: a department of Veterans Affair Cooperative Study. Arthritis Rheum. 1999;42:2325-9. doi: 10.1002/1529-0131(199911)42:11<2325::AID-ANR10>3.0.CO;2-C
7. Spadaro A, Riccieri B, Sili-Scadalli A, et al. Comparision of cyclosporine A and methotrexate in the treatment of psoriatic arthritis. A one year prospective study. Clin Exp Rheum. 1995;13:589-93.
8. Behrens F, Finkenwirth C, Pavelka K, et al. Leflunomide in psoriatic arthritis: results from a large European prospective observational study. Arthritis Care Res (Hoboken). 2013;65(3):464-70. doi: 10.1002/acr.21848
9. Ash Z, Gaujoux-Viala C, Gossec L, et al. A systematic literature review of drug therapies for the treatment of psoriatic arthritis: current evidence and meta-analysis informing the EULAR recommendations for the management of psoriatic arthritis. Ann Rheum Dis. 2012;71:319-26. doi: 10.1136/ard.2011.150995
10. Gossec L, Smolen JS, Gaujoux-Viala C, et al. European League Against Rheumatism recommendations for the management of psoriatic arthritis with pharmacological therapies. Ann Rheum Dis. 2012;71:4-12. doi: 10.1136/annrheumdis-2011-200350
11. Menter A, Korman NJ, Elmets CA, et al. Guidelines of care for the management of psoriasis and psoriatic arthritis: section 4. Guidelines of care for the management and treatment of psoriasis with traditional systemic agents. J Am Acad Dermatol. 2009;61:451-85. doi: 10.1016/j.jaad.2009.03.027
12. Shear NJ. Fulfilling an unmet need in psoriasis: do biologics hold the key to improved tolerability? Drug Saf. 2006;29:49-66. doi: 10.2165/00002018-200629010-00004
13. Houslay MD, Schafer P, Zhang KY. Keynote review: phosphodiesterase-4 as a therapeutic target. Drug Discov Today. 2005;10:1503-19. doi: 10.1016/S1359-6446(05)03622-6
14. Tenor H, Hedbom E, Hauselmann HJ, et al. Phosphodiesterase isoenzyme families in human osteoarthritis chondrocytes-functional importance of phosphodiesterase 4. Br J Pharmacol. 2002;135:609-18. doi: 10.1038/sj.bjp.0704480
15. Manning CD, Burman M, Christensen SB, et al. Suppression of human inflammatory cell function by subtype-selective PDE4 inhibitors correlates with inhibition of PDE4A and PDE4B. Br J Pharmacol. 1999;128:1393-8. doi: 10.1038/sj.bjp.0702911
16. Barber R, Baillie GS, Bergmann R, et al. Differential expression of PDE4 cAMP phosphodiesterase isoforms in inflammatory cells of smokers with COPD, smokers without COPD, and nonsmokers. Am J Physiol Lung Cell Mol Physiol. 2004;287:L332-43. doi: 10.1152/ajplung.00384.2003
17. Bjorgo E, Tasken K. Role of cAMP phosphodiesterase 4 in regulation of T-cell function. Crit Rev Immunol. 2006;26:443-51. doi: 10.1615/CritRevImmunol.v26.i5.40
18. Schafer P. Apremilast mechanism of action and application to psoriasis and psoriatic arthritis. Biochem Pharmacol. 2012;83:1583-90. doi: 10.1016/j.bcp.2012.01.001
19. 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;159:842-55. doi: 10.1111/j.1476-5381.2009.00559.x
20. Wittmann M, Helliwell PS. Phosphodiesterase 4 inhibition in the treatment of psoriasis, psoriatic arthritis and other chronic inflammatory diseases. Dermatol Ther (Heidelb). 2013;3:1-15. doi: 10.1007/s13555-013-0023-0
21. Capone L, Rogovitz A, Gandhi AK, et al. Anti-inflammatory activity of apremilast against T cells, chondrocytes, and rheumatoid arthritis synovial fibroblasts in vitro. Arthritis Rheum. 2011;63(10 Suppl):1844.
22. Gottlieb AB, Strober B, Krueger JG. An open-label, singlearm pilot study in patients with severe plaque-type psoriasis treated with an oral anti-inflammatory agent, apremilast. Curr Med Res Opin. 2008;24:1529-38. doi: 10.1185/030079908X301866
23. McCann FE, Palfreeman AC, Andrews M, et al. Apremilast, a novel PDE4 inhibitor, inhibits spontaneous production of tumour necrosis factor-alpha from human rheumatoid synovial cells and ameliorates experimental arthritis. Arthritis Res Ther. 2010;12:R107. doi: 10.1186/ar3041
24. Gottlieb AB, Matheson RT, Menter A, et al. Efficacy, tolerability, and pharmacodynamics of apremilast in recalcitrant plaque psoriasis: A phase II open-label study. J Drugs Dermatol. 2013;12:888-97.
25. Pathan E, Abraham S, van Rossen E, et al. Efficacy and safety of apremilast, an oral phosphodiesterase 4 inhibitor, in ankylosing spondylitis. Ann Rheum Dis. 2013;72:1475-80. doi: 10.1136/annrheumdis-2012-201915
26. Genovese MC, Jarosova K, Cieslak D, et al. Apremilast in patients with active rheumatoid arthritis: A phase II, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Arthritis Rheum. 2015 Jul;67(7):1703-10. doi: 10.1002/art.39120
27. Hatemi G, Melikoglu M, Tunc R, et al. Apremilast for Behcet’s syndrome – a phase 2, placebo-controlled study. N Engl J Med. 2015;372:1510-8. doi: 10.1056/NEJMoa1408684
28. Papp K, Cather J, Rosoph L, et al. Efficacy of apremilast in the treatment of moderate to severe psoriasis: A randomised controlled trial. Lancet. 2012;380:738-46. doi: 10.1016/S0140-6736(12)60642-4
29. Papp K, Reich K, Leonardi CL, et al. Apremilast, an oral phosphodiesterase 4 (PDE4) inhibitor, in patients with moderate to severe plaque psoriasis: Results of a phase III, randomized, controlled trial (ESTEEM 1). J Am Acad Dermatol. 2015;73:37-49. doi: 10.1016/j.jaad.2015.03.049
30. Schett G, Wollenhautpt 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;64:3156-67. doi: 10.1002/art.34627
31. Kavanaugh A, Mease PJ, Gomez-Reino JJ, et al. Treatment of psoriatic arthritis in a phase 3, randomized controlled trial with apremilast, an oral phosphodiesterase 4 inhibitor. Ann Rheum Dis. 2014;73:1020-6. doi: 10.1136/annrheumdis-2013-205056
32. Cutolo M, Myerson GE, Fleischmann RM, et al. Long-term (52week) results of a phase 3, randomized, controlled trial of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis (PALACE 2). Arthritis Rheum. 2013;65(10 Suppl):S346-7.
33. Edwards CJ, Blanco FJ, Crowley J, et al. Long-term (52-week) results of a phase 3, randomized, controlled trial of apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis and current skin involvement (PALACE 3). Arthritis Rheum. 2013;65(10 Suppl):S132.
34. Edwards CJ, Blanco FJ, Crowley J, et al. Apremilast, an oral phosphodiesterase 4 inhibitor, in patients with psoriatic arthritis and current skin involvement: a phase III, randomised, controlled trial (PALACE 3). Ann Rheum Dis. 2016;75:1065-73. doi: 10.1136/annrheumdis-2015-207963
35. Wells AF, Edwards CJ, Adebajo AO, et al. Apremilast in the treatment of DMARD naive psoriatic arthritis patients: results of a phase 3 randomized controlled trial (PALACE 4). ACR meeting, San Diego, 2013. Abstract L4.
36. Kavanaugh A, Mease PJ, Gomez-Reino JJ, et al. Longterm (52week) Results of a Phase III Randomized, Controlled Trial of Apremilast with Psoriatic Arthritis. J Rheumatol. 2015;42:479-88. doi: 10.3899/jrheum.140647
37. Mease PJ, Kavanaugh A, Gladman DD, et al. Long-term safety and tolerability of apremilast, an oral phospho-diesterase 4 inhibitor, in patients with psoriatic arthritis: Pooled safety analysis of three Phase 3, randomized, controlled trials. Arthritis Rheum. 2013;65(10 Suppl.):S131-2.
38. Celgene International Sarl, Apremilast achieves statistical significance for the primary endpoint of the first phase III study (PALACE-1) in patients with psoriatic arthritis [press release]. Available from: http://ir.celgene.com/phoenix.zhtml?c=111960&p=irolnewsArticle&ID=1714113&highlight= (Accessed August 6, 2013).
39. Goldenberg MM. Pharmaceutical Approval Update. PT. 2014 Jun; 39(6):415-416, 423.
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For citations:
Korsakova Yu.L., Denisov L.N. THE EFFICACY AND SAFETY OF THE NEW DRUG APREMILAST FOR THE TREATMENT OF PSORIASIS AND PSORIATIC ARTHRITIS. Rheumatology Science and Practice. 2016;54(5):572-577. https://doi.org/10.14412/1995-4484-2016-572-577
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