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Current Dermatology Reports

Erschienen in:

01.03.2020 | Psoriasis (J Wu, Section Editor)

Bimekizumab

verfasst von: Andrew Blauvelt, Andrea Chiricozzi, Benjamin D. Ehst

Erschienen in: Current Dermatology Reports | Ausgabe 1/2020

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Abstract

Purpose of Review

Bimekizumab, a novel monoclonal antibody directed against both interleukin (IL)-17A and IL-17F, is in clinical development as a treatment for psoriasis and psoriatic arthritis. The purpose of this review is to highlight the roles of IL-17A and IL-17F in psoriatic inflammation as well as the clinical data on bimekizumab that has been reported to date.

Recent Findings

Phase 2 efficacy results with bimekizumab have demonstrated high levels of rapid skin clearance in psoriasis patients, and high levels of joint disease improvement in psoriatic arthritis patients. Thus far, safety concerns have been limited to cases of mucocutaneous candidiasis, which have been mild-to-moderate and manageable in most instances.

Summary

IL-17A and IL-17F are key pro-inflammatory effector cytokines that are over-expressed in psoriatic skin and joints. Bimekizumab, which targets both IL-17A and IL-17F, has shown great promise thus far as a new treatment for patients with psoriasis and psoriatic arthritis. Confirmatory efficacy and safety results in phase 3 studies for these diseases are eagerly anticipated.

• Ortega C, Fernández AS, Carrillo JM, Romero P, Molina IJ, Moreno JC, et al. IL-17-producing CD8+ T lymphocytes from psoriasis skin plaques are cytotoxic effector cells that secrete Th17-related cytokines. J Leukoc Biol. 2009;86:435–43 Early characterization of IL-17-producing cells within psoriatic skin. CrossRefPubMed

Hijnen D, Knol EF, Gent YY, Giovannone B, Beijn SJ, Kupper TS, et al. CD8(+) T cells in the lesional skin of atopic dermatitis and psoriasis patients are an important source of IFN-g, IL-13, IL-17, and IL-22. J Invest Dermatol. 2013;133:973–9.CrossRefPubMed

• Lowes MA, Kikuchi T, Fuentes-Duculan J, Cardinale I, Zaba LC, Haider AS, et al. Psoriasis vulgaris lesions contain discrete populations of Th1 and Th17 T cells. J Invest Dermatol. 2008;128:1207–11 Early report distinguishing discrete populations of Th17 and Th1 cells within psoriatic skin. CrossRefPubMed

Res PC, Piskin G, de Boer OJ, van der Loos CM, Teeling P, Bos JD, et al. Overrepresentation of IL-17 and IL-22 producing CD8 T cells in lesional skin suggests their involvement in the pathogenesis of psoriasis. PLoS One. 2010;5:e14108.CrossRefPubMedPubMedCentral

Chiricozzi A, Romanelli P, Volpe E, Borsellino G, Romanelli M. Scanning the immunopathogenesis of psoriasis. Int J Mol Sci. 2018;19:E179.CrossRefPubMed

• Blauvelt A, Chiricozzi A. The immunologic role of IL-17 in psoriasis and psoriatic arthritis pathogenesis. Clin Rev Allergy Immunol. 2018;55:379–90 Recent comprehensive review on the roles IL-17 family members play in psoriatic inflammation. CrossRefPubMedPubMedCentral

Martin DA, Towne JE, Kricorian G, Klekotka P, Gudjonsson JE, Krueger JG, et al. The emerging role of IL-17 in the pathogenesis of psoriasis: preclinical and clinical findings. J Invest Dermatol. 2013;133:17–26.CrossRefPubMed

Marinoni B, Ceribelli A, Massarotti MS, Selmi C. The Th17 axis in psoriatic disease: pathogenetic and therapeutic implications. Auto Immun Highlights. 2014;5:9–19.CrossRefPubMedPubMedCentral

• Rizzo HL, Kagami S, Phillips KG, Kurtz SE, Jacques SL, Blauvelt A. IL-23-mediated psoriasis-like epidermal hyperplasia is dependent on IL-17. J Immunol. 2011;186:1495–502 Established IL-17-mediated cutaneous effects as downstream from IL-23 signaling in skin of mice. CrossRefPubMed

10.

Nakajima K, Kanda T, Takaishi M, Shiga T, Miyoshi K, Nakajima H, et al. Distinct roles of IL-23 and IL-17 in the development of psoriasis-like lesions in a mouse model. J Immunol. 2011;186:4481–9.CrossRefPubMed

11.

• Kagami S, Rizzo HL, Lee JJ, Koguchi Y, Blauvelt A. Circulating Th17, Th22, and Th1 cells are increased in psoriasis. J Invest Dermatol. 2010;130:1373–83 Extensive characterization of distinct inflammatory T cell subsets in the blood of psoriasis patients.CrossRefPubMed

12.

Chiricozzi A, Cannizzaro MV, Salandri GA, Marinari B, Pitocco R, Dattola A, et al. Increased levels of IL-17 in tear fluid of moderate-to-severe psoriatic patients is reduced by adalimumab therapy. J Eur Acad Dermatol Venereol. 2016;30:e128–9.PubMed

13.

Chiricozzi A, Suárez-Fariñas M, Fuentes-Duculan J, Cueto I, Li K, Tian S, et al. Increased expression of interleukin-17 pathway genes in nonlesional skin of moderate-to-severe psoriasis vulgaris. Br J Dermatol. 2016;174:136–45.CrossRefPubMed

14.

Suárez-Fariñas M, Li K, Fuentes-Duculan J, Hayden K, Brodmerkel C, Krueger JG. Expanding the psoriasis disease profile: interrogation of the skin and serum of patients with moderate-to-severe psoriasis. J Invest Dermatol. 2012;132:2552–64.CrossRefPubMedPubMedCentral

15.

Guttman-Yassky E, Suárez-Fariñas M, Chiricozzi A, Nograles KE, Shemer A, Fuentes-Duculan J, et al. Broad defects in epidermal cornification in atopic dermatitis identified through genomic analysis. J Allergy Clin Immunol. 2009;124:1235–1244.e58.CrossRefPubMed

16.

Keijsers RRMC, Hendriks AGM, van Erp PEJ, van Cranenbroek B, van de Kerkhof PCM, Koenen HJPM, et al. In vivo induction of cutaneous inflammation results in the accumulation of extracellular trap-forming neutrophils expressing RORgt and IL-17. J Invest Dermatol. 2014;134:1276–84.CrossRefPubMed

17.

Lin AM, Rubin CJ, Khandpur R, Wang JY, Riblett M, Yalavarthi S, et al. Mast cells and neutrophils release IL-17 through extracellular trap formation in psoriasis. J Immunol. 2011;187:490–500.CrossRefPubMed

18.

Cai Y, Shen X, Ding C, Qi C, Li K, Li X, et al. Pivotal role of dermal IL-17-producing T cells in skin inflammation. Immunity. 2011;35:596–610.CrossRefPubMedPubMedCentral

19.

Siebert S, Sweet K, Dasgupta B, Campbell K, McInnes IB, Loza MJ. Responsiveness of serum C-reactive protein, interleukin-17A, and interleukin-17F levels to ustekinumab in psoriatic arthritis: lessons from two phase III, multicenter, double-blind, placebo-controlled trials. Arthritis Rheum. 2019;71:1660–9.CrossRef

20.

Zaba LC, Cardinale I, Gilleaudeau P, Sullivan-Whalen M, Suárez-Fariñas M, Fuentes-Duculan J, et al. Amelioration of epidermal hyperplasia by TNF inhibition is associated with reduced Th17 responses. J Exp Med. 2007;204:3183–94.CrossRefPubMedPubMedCentral

21.

• Chiricozzi A, Nograles KE, Johnson-Huang LM, Fuentes-Duculan J, Cardinale I, Bonifacio KM, et al. IL-17 induces an expanded range of downstream genes in reconstituted human epidermis model. PLoS One. 2014;9:e90284 Characterization of IL-17-mediated downstream gene expression in keratinocytes. CrossRefPubMedPubMedCentral

22.

Arakawa A, Siewert K, Stöhr J, Besgen P, Kim SM, Rühl G, et al. Melanocyte antigen triggers autoimmunity in human psoriasis. J Exp Med. 2015;212:2203–12.CrossRefPubMedPubMedCentral

23.

Lande R, Botti E, Jandus C, Dojcinovic D, Fanelli G, Conrad C, et al. The antimicrobial peptide LL37 is a T-cell autoantigen in psoriasis. Nat Commun. 2014;5:5621.CrossRefPubMed

24.

Nishimoto S, Kotani H, Tsuruta S, Shimizu N, Ito M, Shichita T, et al. Th17 cells carrying TCR recognizing epidermal autoantigen induce psoriasis-like skin inflammation. J Immunol. 2013;191:3065–72.CrossRefPubMed

25.

Krueger JG. An autoimmune “attack” on melanocytes triggers psoriasis and cellular hyperplasia. J Exp Med. 2015;212:2186.CrossRefPubMedPubMedCentral

26.

Fuentes-Duculan J, Bonifacio KM, Hawkes JE, Kunjravia N, Cueto I, Li X, et al. Autoantigens ADAMTSL5 and LL37 are significantly upregulated in active psoriasis and localized with keratinocytes, dendritic cells and other leukocytes. Exp Dermatol. 2017;26:1075–82.CrossRefPubMedPubMedCentral

27.

• Matos TR, O'Malley JT, Lowry EL, Hamm D, Kirsch IR, Robins HS, et al. Clinically resolved psoriatic lesions contain psoriasis-specific IL-17-producing αβ T cell clones. J Clin Invest. 2017;127:4031–41 Detailed characterization of IL-17 producing T cells that remain in healed psoriasis skin that are responsible for psoriasis recurrences. CrossRefPubMedPubMedCentral

28.

• Cheuk S, Wikén M, Blomqvist L, Nylén S, Talme T, Ståhle M, et al. Epidermal Th22 and Tc17 cells form a localized disease memory in clinically healed psoriasis. J Immunol. 2014;192:3111–20 Initial characterization of Tc17 cells that remain in healed psoriasis skin that are responsible for psoriasis recurrences. CrossRefPubMedPubMedCentral

29.

Gallais Sérézal I, Classon C, Cheuk S, Barrientos-Somarribas M, Wadman E, Martini E, et al. Resident T cells in resolved psoriasis steer tissue responses that stratify clinical outcome. J Invest Dermatol. 2018;138:1754–63.CrossRefPubMed

30.

Johnston A, Fritz Y, Dawes SM, Diaconu D, Al-Attar PM, Guzman AM, et al. Keratinocyte overexpression of IL-17C promotes psoriasiform skin inflammation. J Immunol. 2013;190:2252–62.CrossRefPubMed

31.

Norsgaard H, Hebsgaard J, Ewald D, Tiirikainen M, Lovato P, Bertelsen M, et al. Multiple IL-17 cytokines, signalling through IL-17 receptor A, drive inflammatory pathways in psoriasis. Poster P1974 presented at the 27th annual European Academy of Dermatology and Venerology (EADV) Congress in Paris, 2018.

32.

• Zrioual S, Ecochard R, Tournadre A, Lenief V, Cazalis MA, Miossec P. Genome-wide comparison between IL-17A- and IL-17F-induced effects in human rheumatoid arthritis synoviocytes. J Immunol. 2009;182:3112–20 Delineation of biologic effects of IL-17A versus IL-17F in synoviocytes. CrossRefPubMed

33.

Guilloteau K, Paris I, Pedretti N, Boniface K, Juchaux F, Huguier V, et al. Skin inflammation induced by the synergistic action of IL-17A, IL-22, oncostatin M, IL-1-α, and TNF-α recapitulates some features of psoriasis. J Immunol. 2010;184:5263–70.CrossRefPubMed

34.

Noack M, Beringer A, Miossec P. Additive or synergistic interactions between IL-17A or IL-17F and TNF or IL-1β depend on the cell type. Front Immunol. 2019;10:1726.CrossRefPubMedPubMedCentral

35.

• Zrioual S, Ecochard R, Tournadre A, Lenief V, Cazalis MA, Miossec P. Genome-wide comparison between IL-17A- and IL-17F-induced effects in human rheumatoid arthritis synoviocytes. J Immunol. 2009;182:3112–20 Delineation of downstream gene expression induced by IL-17A versus IL-17F in synoviocytes. CrossRefPubMed

36.

• Chiricozzi A, Guttman-Yassky E, Suarez-Farinas M, Nograles KE, Tian S, Cardinale I, et al. Integrative responses to IL-17 and TNF-alpha in human keratinocytes account for key inflammatory pathogenic circuits in psoriasis. J Invest Dermatol. 2011;131:677–87 Key description of biologic synergy that occurs with TNF-α and IL-17 within psoriasis. CrossRefPubMed

37.

Chabaud M, Fossiez F, Taupin JL, Miossec P. Enhancing effect of IL-17 on IL-1–induced IL-6 and leukemia inhibitory factor production by rheumatoid arthritis synoviocytes and its regulation by Th2 cytokines. J Immunol. 1998;161:409–14.PubMed

38.

Bonaventura P, Lamboux A, Albarede F, Miossec P. Differential effects of TNF-alpha and IL-1beta on the control of metal metabolism and cadmium-induced cell death in chronic inflammation. PLoS One. 2018;13:e0196285.CrossRefPubMedPubMedCentral

39.

Maroof A, Okoye R, Smallie T, et al. Bimekizumab dual inhibition of IL-17A and IL-17F provides evidence of IL-17F contribution to chronic inflammation in disease-relevant cells. Ann Rheum Dis. 2017;76:A1–A103 02.13.

40.

Maroof A, Smallie T, Archer S, Baeten D, Archer S, Simpson C, et al. Dual IL-17A and IL-17F inhibition with bimekizumab provides evidence for IL-17F contribution to immune-mediated inflammatory skin response. J Invest Dermatol. 2017;137:S120.CrossRef

41.

Maroof A, Baeten D, Archer S, Griffiths M, Shaw S. IL-17F contributes to human chronic inflammation in synovial tissue: preclinical evidence with dual IL-17A and IL-17F inhibition with bimekizumab in psoriatic arthritis. Ann Rheum Dis. 2017;76:A13 -A.CrossRef

42.

•• Glatt S, Baeten D, Baker T, Griffiths M, Ionescu L, ADG L, et al. Dual IL-17A and IL-17F neutralisation by bimekizumab in psoriatic arthritis: evidence from preclinical experiments and a randomised placebo-controlled clinical trial that IL-17F contributes to human chronic tissue inflammation. Ann Rheum Dis. 2018;77:523–32 Delineation of in vitro biologic effects of dual blockade of IL-17A/IL-17F versus single blockade of each cytokine alone as well as description of initial clinical study in psoriatic arthritis patients. CrossRefPubMed

43.

•• Glatt S, Helmer E, Haier B, et al. First-in-human randomized study of bimekizumab, a humanized monoclonal antibody and selective dual inhibitor of IL-17A and IL-17F, in mild psoriasis. Br J Clin Pharmacol. 2017;83:991–1001 First-in-human phase 1 study of bimekizumab in psoriasis. CrossRefPubMedPubMedCentral

44.

•• Papp KA, Merola JF, Gottlieb AB, Strimenopoulou F, Price G, Vajjah P, et al. Dual neutralization of both interleukin 17A and interleukin 17F with bimekizumab in patients with psoriasis: results from BE ABLE 1, a 12-week randomized, double-blinded, placebo-controlled phase 2b trial. J Am Acad Dermatol. 2018;79:277–286.e10 Phase 2 week 12 results of bimekizumab for psoriasis showing rapid clearing of skin. CrossRefPubMed

45.

•• Blauvelt A, Papp KA, Merola JF, Gottlieb AB, Cross N, Madden C, et al. Dual neutralisation of interleukin (IL)–17A and IL–17F with bimekizumab in moderate-to-severe plaque psoriasis: 60-week results from a randomised, double-blinded, phase 2b extension study. Ann Rheum Dis. 2019;78:1834 Phase 2 week 60 results of bimekizumab for psoriasis showing high levels of skin clearance and durability of responses over time.

46.

•• Ritchlin CT, Kavanaugh A, Merola JF, Schett G, Scher JU, Warren RB, et al. Dual neutralization of IL-17A and IL-17F with bimekizumab in patients with active PsA: results from a 48-week phase 2b, randomized, double-blind, placebo-controlled, dose-ranging study. Arthritis Rheum. 2018;70:10 Phase 2 week 48 efficacy and safety results in psoriatic arthritis patients.

47.

van der Heijde D, Gensler L, Deodhar A, Baraliakos X, Poddubnyy D, Farmer MK, et al. Dual neutralisation of IL-17A and IL-17F with bimekizumab in patients with active ankylosing spondylitis (AS): 12-week results from a phase 2b, randomised, double-blind, placebo-controlled, dose-ranging study. Ann Rheum Dis. 2018;77:70.CrossRef

48.

Glatt S, Taylor PC, McInnes IB, Schett G, Landewé R, Baeten D, et al. Efficacy and safety of bimekizumab as add-on therapy for rheumatoid arthritis in patients with inadequate response to certolizumab pegol: a proof-of-concept study. Ann Rheum Dis. 2019;78:1033–40. https://doi.org/10.1136/annrheumdis-2018-214943.CrossRefPubMed

Titel: Bimekizumab
verfasst von: Andrew Blauvelt
Andrea Chiricozzi
Benjamin D. Ehst
Publikationsdatum: 01.03.2020
Verlag: Springer US
Erschienen in: Current Dermatology Reports / Ausgabe 1/2020
Elektronische ISSN: 2162-4933
DOI: https://doi.org/10.1007/s13671-020-00286-2

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