Eficacia de ustekinumab en el tratamiento de la psoriasis moderada-grave

Jiménez-Puya, R.; Moreno, J.C.

doi:10.1016/S0001-7310(12)70004-2

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Información del artículo

Resumen

Bibliografía

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Estadísticas

Resumen

El avance en el conocimiento de la fisiopatología de la psoriasis ha permitido producir nuevas terapias más eficaces y seguras en el manejo de la enfermedad, primero con el bloqueo del factor de necrosis tumoral α y, posteriormente, de forma más específica el de la vía interleucina 12/23. Las interleucinas 12 y 23 desempeñan un importante rol en la cascada inmunitaria de la psoriasis, compartiendo la subunidad proteica p40 que permite bloquear ambas citocinas, actuando de forma más concreta en la producción de la placa inflamatoria.

La eficacia de ustekinumab se ha contrastado en diversos ensayos clínicos en fase III (PHOENIX 1 y 2), y su desarrollo clínico abarca el mayor número de pacientes estudiado con un agente biológico, siendo también el único en compararse de forma head to head con etanercept, un agente bloqueante del factor de necrosis tumoral α (estudio ACCEPT).

Palabras clave:

Ustekinumab

Psoriasis

IL-12

IL-23

Subunidad p40

Abstract

Improved understanding of the pathophysiology of psoriasis has led to the development of biologic agents that offer improved safety and efficacy in the treatment of this disease. TNF inhibitors were the first biologics to be added to the therapeutic arsenal, and these were followed by agents that selectively block IL-12 and IL-23, two cytokines that play an important role in the immune cascade that leads to psoriasis. By targeting the p40 subunit shared by these cytokines, ustekinumab blocks the activity of IL 12/23, thereby reducing skin inflammation.

The efficacy of ustekinumab has been analyzed in phase III clinical trials (PHOENIX 1 and 2) and its clinical development program was the largest ever for a biologic agent. Ustekinumab has also been compared to the TNF inhibitor etanercept in the first-ever head-to-head comparison of biologic agents in psoriasis (the ACCEPT psoriasis trial).

Keywords:

Ustekinumab

Psoriasis

IL 12

IL-23

p40 subunit

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Bibliografía

[1.]

M.P. Schön, W.H. Boehncke.

Psoriasis.

N Engl J Med, 352 (2005), pp. 1899-1912

http://dx.doi.org/10.1056/NEJMra041320 | Medline

[2.]

C.A. Hunter.

New IL-12-family members: IL-23 and IL-17 cytokines with divergent functions.

Nat Rev Immunol, 5 (2005), pp. 521-531

http://dx.doi.org/10.1038/nri1648 | Medline

[3.]

A.L. Chien, J.T. Elder, C.N. Ellis.

Ustekinumab: a new option in psoriasis therapy.

Drugs, 69 (2009), pp. 1141-1152

Medline

[4.]

C.L. Leonardi, A.B. Kimball, K.A. Papp, N. Yeilding, C. Guzzo, Y. Wang, PHOENIX 1 study investigators, et al.

Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 76-week results from a randomized, double-blind, placebo-controlled trial (PHOENIX 1).

Lancet, 371 (2008), pp. 1665-1674

http://dx.doi.org/10.1016/S0140-6736(08)60725-4 | Medline

[5.]

K.A. Papp, R.G. Langley, M. Lebwohl, G.G. Krueger, P. Szapary, N. Yeilding, PHOENIX 2 study investigators, et al.

Efficacy and safety of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with psoriasis: 52-week results from a randomized, double-blind, placebo-controlled trial (PHOENIX 2).

Lancet, 371 (2008), pp. 1675-1684

http://dx.doi.org/10.1016/S0140-6736(08)60726-6 | Medline

[6.]

M. Lebwohl, N. Yeilding, P. Szapary, Y. Wang, S. Li, Y. Zhu, et al.

Impact of weight on the efficacy and safety of ustekinumab in patients with moderate to severe psoriasis: rationale for dosing recommendations.

J Am Acad Dermatol, 63 (2010), pp. 571-579

http://dx.doi.org/10.1016/j.jaad.2009.11.012 | Medline

[7.]

Ustekunimab SPC [consultado 11/02/2009]. Disponible en: http://www.emea.europa.eu/humandocs/PDFs/EPAR/stelara/H-958-PI-en.pdf.

[8.]

Rich P, Feldman S, Vender R, Ortonne JP, Rustin M, et al. Ustekinumab demonstrates rapid onset of efficacy in the treatment of moderate-to-severe psoriasis. Poster P040 presentado en el Congress of the Psoriasis InternationalNetwork. Paríes, Jul 2010.

[9.]

Kimball A, Goffe B, Bissonnette R, Yeilding N, Li S, et al. Efficacy of ustekinumab is sustained through 3 years of treatment for patients with moderate-to-severe psoriasis maintained on q12 week dosing based on body weight. Poster presentado en el Congress of the Psoriasis International Network; París, Francia. Jul 2010 Julio. Póster P044.

[10.]

Gordon K, Lambert J, Gratton D, Baker D, Matheson R, et al. Sustained efficacy of ustekinumab for the treatment of moderate to severe psoriasis in initial responders continuing with maintenance therapy through year 3. Poster presentado en el Congress of the Psoriasis International Network; París, Francia. Jul 2010. Póster P046.

[11.]

Ghislain PD, Poulin Y, Wasel N, Sofen H, Yeilding N, et al. Maintenance of long-term efficacy of ustekinumab through year 3 for patients with moderate-to-severe psoriasis. Poster presentado en el 19.° Congreso de la European Academy of Dermatology and Venereology; Gothenburg, Sweden. Oct 2010. Poster P589.

[12.]

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