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Open Access 01-06-2016 | Review

Brodalumab for the Treatment of Psoriasis: A Review of Phase III Trials

Authors: Benjamin Farahnik, Kourosh Beroukhim, Michael Abrouk, Mio Nakamura, Tian Hao Zhu, Rasnik Singh, Kristina Lee, Tina Bhutani, John Koo

Published in: Dermatology and Therapy | Issue 2/2016

Abstract

Introduction

Interleukin (IL)-17 inhibitors are the most recent class of monoclonal antibodies approved by the FDA for psoriasis treatment. Preclinical and phase II studies of brodalumab, a high-affinity IL-17 receptor monoclonal antibody, have been encouraging.

Methods

We conducted a literature search using the PubMed database in order to assess the efficacy and safety profile of brodalumab. The search included the following key words: “psoriasis” and “IL-17” or “brodalumab.” We also reviewed citations within articles to identify relevant sources.

Results

At week 12, the proportion of patients attaining a 75% improvement from the baseline Psoriasis Area and Severity Index (PASI 75) was similar among the three phase III trials (AMAGINE-1, 83%; AMAGINE-2, 86%; AMAGINE-3, 85%). Brodalumab remained efficacious through 52 weeks of treatment. It maintained a satisfactory safety profile; the most frequently reported adverse events consisted of nasopharyngitis, headache, upper respiratory tract infection, and arthralgia.

Conclusion

Use of brodalumab revealed prompt clinical improvement and a favorable short-term safety profile in phase III trials, although further extension studies are needed to assess long-term safety. Based on the results, brodalumab appears to be a potent therapeutic option for patients with moderate-to-severe plaque-type psoriasis.

Rachakonda T, Schupp C, Armstrong A. Psoriasis prevalence among adults in the United States. J Am Acad Dermatol. 2014;. doi:10.1016/j.jaad.2013.11.013.

Feldman SR, Malakouti M, Koo JY. Social impact of the burden of psoriasis: effects on patients and practice. Dermatol Online J. 2014;20(8):1–8.

Lebwohl MG, Bachelez H, Barker J, et al. Patient perspectives in the management of psoriasis: results from the population-based Multinational Assessment of Psoriasis and Psoriatic Arthritis Survey. J Am Acad Dermatol. 2014;70(5):871–81.e1–30. doi:10.1016/j.jaad.2013.12.018.

Weaver CT, Hatton RD, Mangan PR, Harrington LE. IL-17 family cytokines and the expanding diversity of effector T cell lineages. Annu Rev Immunol. 2007;25:821–52. doi:10.1146/annurev.immunol.25.022106.141557.CrossRefPubMed

Krueger JG, Fretzin S, Suárez-Fariñas M, et al. IL-17A is essential for cell activation and inflammatory gene circuits in subjects with psoriasis. J Allergy Clin Immunol. 2012;130(1):145–54.e9. doi:10.1016/j.jaci.2012.04.024.

Chang SH, Dong C. A novel heterodimeric cytokine consisting of IL-17 and IL-17F regulates inflammatory responses. Cell Res. 2007;17(5):435–40. doi:10.1038/cr.2007.35.PubMed

Chan JR, Blumenschein W, Murphy E, et al. IL-23 stimulates epidermal hyperplasia via TNF and IL-20R2-dependent mechanisms with implications for psoriasis pathogenesis. J Exp Med. 2006;203(12):2577–87. doi:10.1084/jem.20060244.CrossRefPubMedPubMedCentral

Lowes MA, Kikuchi T, Fuentes-Duculan J, et al. Psoriasis vulgaris lesions contain discrete populations of Th1 and Th17 T cells. J Invest Dermatol. 2008;128(5):1207–11. doi:10.1038/sj.jid.5701213.CrossRefPubMed

Pappu R, Ramirez-Carrozzi V, Sambandam A. The interleukin-17 cytokine family: critical players in host defence and inflammatory diseases. Immunology. 2011;134(1):8–16. doi:10.1111/j.1365-2567.2011.03465.x.CrossRefPubMedPubMedCentral

10.

Tang C, Chen S, Qian H, Huang W. Interleukin-23: as a drug target for autoimmune inflammatory diseases. Immunology. 2012;135(2):112–24. doi:10.1111/j.1365-2567.2011.03522.x.CrossRefPubMedPubMedCentral

11.

Ritchlin C, Rahman P, Kavanaugh A, et al. Efficacy and safety of the anti-IL-12/23 p40 monoclonal antibody, ustekinumab, in patients with active psoriatic arthritis despite conventional non-biological and biological anti-tumour necrosis factor therapy: 6-month and 1-year results of the phase 3, multicentre, double-blind, placebo-controlled, randomised PSUMMIT 2 trial. Ann Rheum Dis. 2014;73(6):990–9. doi:10.1136/annrheumdis-2013-204655.CrossRefPubMedPubMedCentral

12.

Laan M, Cui ZH, Hoshino H, et al. Neutrophil recruitment by human IL-17 via C-X-C chemokine release in the airways. J Immunol. 1999;162(4):2347–52. http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=9973514. Accessed 11 Feb 2015.PubMed

13.

Kao C-YY, Chen Y, Thai P, et al. IL-17 markedly up-regulates beta-defensin-2 expression in human airway epithelium via JAK and NF-kappaB signaling pathways. J Immunol. 2004;173(5):3482–91. http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=15322213. Accessed 11 Feb 2015.CrossRefPubMed

14.

Numasaki M, Fukushi J, Ono M, et al. Interleukin-17 promotes angiogenesis and tumor growth. Blood. 2003;101(7):2620–7. doi:10.1182/blood-2002-05-1461.CrossRefPubMed

15.

Li J, Li D, Tan Z. The expression of interleukin-17, interferon-gamma, and macrophage inflammatory protein-3 alpha mRNA in patients with psoriasis vulgaris. J Huazhong Univ Sci Technol Med Sci. 2004;24(3):294–6.CrossRefPubMed

16.

Ariza M-EE, Williams MV, Wong HK. Targeting IL-17 in psoriasis: from cutaneous immunobiology to clinical application. Clin Immunol. 2013;146(2):131–9. doi:10.1016/j.clim.2012.12.004.CrossRefPubMed

17.

Yilmaz SB, Cicek N, Coskun M, Yegin O, Alpsoy E. Serum and tissue levels of IL-17 in different clinical subtypes of psoriasis. Arch Dermatol Res. 2012;304(6):465–9. doi:10.1007/s00403-012-1229-1.CrossRefPubMed

18.

Brown G, Malakouti M, Wang E, Koo J, Levin E. Anti-IL-17 phase II data for psoriasis: a review. J Dermatol Treat. 2014;26(1):32–6. doi:10.3109/09546634.2013.878448.CrossRef

19.

Kagami S, Rizzo HL, Lee JJ, Koguchi Y, Blauvelt A. Circulating Th17, Th22, and Th1 cells are increased in psoriasis. J Invest Dermatol. 2010;130(5):1373–83. doi:10.1038/jid.2009.399.CrossRefPubMed

20.

Papp K, Reich K, Leonardi C, et al. Efficacy and safety of brodalumab in patients with moderate to severe plaque psoriasis: results of AMAGINE-1, a phase 3, randomized, double-blind, placebo controlled study through week 12. In: Presented at the 73rd annual meeting of the American academy of dermatology; 2015 March 20–24; San Francisco, CA.

21.

Lebwohl M, Strober B, Menter A, et al. Phase 3 studies comparing brodalumab with ustekinumab in psoriasis. N Engl J Med. 2015;. doi:10.1056/NEJMoa1503824.PubMedCentral

22.

Revicki DA, Willian MK, Menter A, Saurat J-HH, Harnam N, Kaul M. Relationship between clinical response to therapy and health-related quality of life outcomes in patients with moderate to severe plaque psoriasis. Dermatology (Basel). 2008;216(3):260–70. doi:10.1159/000113150.CrossRef

23.

Farahnik B, Beroukhim K, Nakamura M, et al. Anti-IL-17 agents for psoriasis: a review of phase III data. J Drugs Dermatol. 2016;15(3):311–6.PubMed

24.

Puel A, Cypowyj S, Bustamante J, et al. Chronic mucocutaneous candidiasis in humans with inborn errors of interleukin-17 immunity. Science. 2011;332(6025):65–8. doi:10.1126/science.1200439.CrossRefPubMedPubMedCentral

25.

Boisson B, Wang C, Pedergnana V, et al. An ACT1 mutation selectively abolishes interleukin-17 responses in humans with chronic mucocutaneous candidiasis. Immunity. 2013;39(4):676–86. doi:10.1016/j.immuni.2013.09.002.CrossRefPubMed

26.

Gupta MA, Gupta AK. Depression and suicidal ideation in dermatology patients with acne, alopecia areata, atopic dermatitis and psoriasis. Br J Dermatol. 1998;139(5):846–50. http://onlinelibrary.wiley.com/resolve/openurl?genre=article&sid=nlm:pubmed&issn=0007-0963&date=1998&volume=139&issue=5&spage=846. Accessed 11 Feb 2015.CrossRefPubMed

27.

Kurd SK, Troxel AB, Crits-Christoph P, Gelfand JM. The risk of depression, anxiety, and suicidality in patients with psoriasis: a population-based cohort study. Arch Dermatol. 2010;146(8):891–5. doi:10.1001/archdermatol.2010.186.PubMedPubMedCentral

28.

Wu JJ. Letter regarding phase 3 studies comparing brodalumab with ustekinumab in psoriasis. J Psoriasis Psoriatic Arthritis. 2016;1:61.

29.

Garber K. Anti-IL-17 mAbs herald new options in psoriasis. Nat Biotechnol. 2012;. doi:10.1038/nbt0612-475.

30.

Langenbruch A, Radtke MA, Krensel M, Jacobi A, Reich K, Augustin M. Nail involvement as a predictor of concomitant psoriatic arthritis in patients with psoriasis. Br J Dermatol. 2014;. doi:10.1111/bjd.13272.PubMed

31.

Mease PJ, McInnes IB, Kirkham B, et al. Secukinumab inhibition of interleukin-17A in patients with psoriatic arthritis. N Engl J Med. 2015;373(14):1329–39. doi:10.1056/NEJMoa1412679.CrossRefPubMed

32.

Raychaudhuri SP. Role of IL-17 in psoriasis and psoriatic arthritis. Clin Rev Allergy Immunol. 2013;44(2):183–93. doi:10.1007/s12016-012-8307-1.CrossRefPubMed

33.

Raychaudhuri SP, Raychaudhuri SK, Genovese MC. IL-17 receptor and its functional significance in psoriatic arthritis. Mol Cell Biochem. 2012;359(1–2):419–29. doi:10.1007/s11010-011-1036-6.CrossRefPubMed

34.

Mease PJ, Genovese MC, Greenwald MW, et al. Brodalumab, an anti-IL17RA monoclonal antibody, in psoriatic arthritis. N Engl J Med. 2014;370(24):2295–306. doi:10.1056/NEJMoa1315231.CrossRefPubMed

35.

McIvor A. Emerging therapeutic options for the treatment of patients with symptomatic asthma. Ann Allergy Asthma Immunol. 2015;. doi:10.1016/j.anai.2015.07.011.PubMed

36.

Yeremenko N, Paramarta JE, Baeten D. The interleukin-23/interleukin-17 immune axis as a promising new target in the treatment of spondyloarthritis. Curr Opin Rheumatol. 2014;26(4):361–70. doi:10.1097/BOR.0000000000000069.CrossRefPubMed

37.

Wu JJ, Poon K-YTY, Channual JC, Shen AY. Association between tumor necrosis factor inhibitor therapy and myocardial infarction risk in patients with psoriasis. Arch Dermatol. 2012;148(11):1244–50. doi:10.1001/archdermatol.2012.2502.CrossRefPubMed

38.

De Boer OJ, van der Meer JJ, Teeling P, et al. Differential expression of interleukin-17 family cytokines in intact and complicated human atherosclerotic plaques. J Pathol. 2010;220(4):499–508. doi:10.1002/path.2667.PubMed

39.

Csiszar A, Ungvari Z. Synergistic effects of vascular IL-17 and TNFalpha may promote coronary artery disease. Med Hypotheses. 2004;63(4):696–8. doi:10.1016/j.mehy.2004.03.009.CrossRefPubMed

40.

Gan EY, Chong W-SS, Tey HL. Therapeutic strategies in psoriasis patients with psoriatic arthritis: focus on new agents. BioDrugs. 2013;27(4):359–73. doi:10.1007/s40259-013-0025-6.CrossRefPubMed

Title: Brodalumab for the Treatment of Psoriasis: A Review of Phase III Trials
Authors: Benjamin Farahnik
Kourosh Beroukhim
Michael Abrouk
Mio Nakamura
Tian Hao Zhu
Rasnik Singh
Kristina Lee
Tina Bhutani
John Koo
Publication date: 01-06-2016
Publisher: Springer Healthcare
Published in: Dermatology and Therapy / Issue 2/2016
Print ISSN: 2193-8210
Electronic ISSN: 2190-9172
DOI: https://doi.org/10.1007/s13555-016-0121-x

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