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Vol. 103. Issue S2.
Actualización del uso de ustekinumab: un ava nce en el tratamiento de la psoriasis
Pages 65-72 (October 2012)
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Vol. 103. Issue S2.
Actualización del uso de ustekinumab: un ava nce en el tratamiento de la psoriasis
Pages 65-72 (October 2012)
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Ustekinumab en la artritis psoriásica y la enfermedad de Crohn
Ustekinumab in Psoriatic Arthritis and Crohn Disease
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5039
R. Queiroa,
Corresponding author
queiro@mixmail.com

Autor para correspondencia.
, D. Ginardb
a Servicio de Reumatología. Hospital Universitario Central de Asturias. Oviedo. Asturias. España
b Servicio de Aparato Digestivo. Hospital Universitario Son Espases. Palma de Mallorca. Mallorca. España
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Resumen

Aunque la indicación principal de ustekinumab (UST) en el momento actual es la psoriasis, su innovador mecanismo de acción aventura otras indicaciones en un futuro próximo, entre ellas, la artritis psoriásica (APs) y la enfermedad de Crohn (EC).

La psoriasis y la APs son entidades donde la interacción de elementos de restricción genética, junto a factores ambientales e inmunológicos juegan un papel clave para dar lugar a las manifestaciones propias de ambas enfermedades. Una de las principales vías patogénicas en estas condiciones es el eje IL-23/Th17, y existen sobradas evidencias para apoyar intervenciones farmacológicas sobre el mismo. En el momento actual, sólo disponemos de un agente con capacidad de actuar sobre esta diana, UST, un anticuerpo monoclonal humano frente a la subunidad común p40 de la IL-12 e IL-23. Aunque disponemos de cierta información sobre su utilidad en el tratamiento de la APs, aún precisamos de más datos sobre su eficacia y seguridad en este campo.

Por otra parte, la EC es una enfermedad inflamatoria crónica de etiología desconocida que afecta al tubo digestivo. El tratamiento consiste en el uso de corticoides, inmunosupresores y anticuerpos anti factor de necrosis tumoral. Algunos pacientes no responden, por lo que es necesario disponer de alternativas de tratamiento, entre las que se encuentra UST. Recientemente, dos estudios fase IIb apuntan a que UST induce y mantiene la respuesta clínica en la EC, principalmente en pacientes con fracaso previo a infliximab y proteína C reactiva elevada en el momento del tratamiento. Aún quedan interrogantes por resolver, como la dosis más eficaz o la vía de administración más adecuada, y se precisan más estudios para evaluar la eficacia y determinar el mejor esquema terapéutico en la EC.

El presente trabajo revisa la información disponible hasta la fecha sobre la utilidad potencial de este nuevo agente en el tratamiento de la APs y la EC.

Palabras clave:
Psoriasis
Artritis psoriásica
Ustekinumab
Eficacia
Enfermedad de Crohn
Interleucina 12/23
Abstract

Although ustekinumab is currently licensed for the treatment of psoriasis, in view of the innovative mechanism of action of this biologic agent, it is reasonable to hypothesize that it will, in the near future, be approved for other indications, such as the treatment of psoriatic arthritis and Crohn disease.

Interactions between genetic, environmental, and immunological factors play a key role in the pathogenesis of both psoriasis and psoriatic arthritis. The IL-23/TH17 axis is one of the main pathogenic pathways in these diseases, and there is ample evidence to support the use of pharmacologic agents targeting this pathway. Ustekinumab, a human monoclonal antibody that binds to the p40 subunit shared by IL-12 and IL-23, is currently the only agent capable of modulating the IL-23/TH17 pathway. While there is some evidence supporting the use of ustekinumab in the treatment of psoriatic arthritis, more data on safety and efficacy are required.

Crohn disease is a chronic inflammatory disease of unknown etiology that affects the digestive tract. It is treated with corticosteroids, immunosuppressants, and anti-TNF agents. Alternative treatments, such as ustekinumab, however, are needed for patients who do not respond to conventional therapy. The results of 2 recent phase IIb studies showed that ustekinumab induced and maintained clinical response in patients with Crohn disease; most of those who responded well had previously been unsuccessfully treated with infliximab and had elevated C reactive protein levels at the time of treatment. Many issues remain to be resolved, including the establishment of an optimal dose and administration route. Further studies are needed to evaluate the efficacy of ustekinumab in Crohn disease and to determine the best treatment regimen.

The present chapter reviews the current evidence on the potential usefulness of ustekinumab in the treatment of psoriatic arthritis and Crohn disease.

Keywords:
Psoriasis
Psoriatic arthritis
Ustekinumab
Efficacy
Crohn disease
Interleukin 12/23
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Bibliografía
[1.]
D.D. Gladman.
Psoriatic arthritis.
Dermatol Ther, 22 (2009), pp. 40-55
[2.]
J.M. Moll, V. Wright.
Psoriatic arthritis.
Semin Arthritis Rheum, 3 (1973), pp. 55-78
[3.]
W. Taylor, D. Gladman, P. Helliwell, A. Marchesoni, P. Mease, H. Mielants, CASPAR Study Group.
Classification criteria for psoriatic arthritis: development of new criteria from a large international study.
Arthritis Rheum, 54 (2006), pp. 2665-2673
[4.]
D.D. Gladman, C. Antoni, P. Mease, D.O. Clegg, P. Nash.
Psoriatic arthritis: epidemiology, clinical features, course, and outcome.
Ann Rheum Dis, 64 (2005), pp. ii14-ii17
[5.]
J.L. Fernández Sueiro, X. Juanola Roura, J.D. Cañete Crespillo, J.C. Torre Alonso, R. García de Vicuña, R. Queiro Silva, et al.
Consensus statement of the Spanish Society of Rheumatology on the management of biologic therapies in psoriatic arthritis.
Reumatol Clin, 7 (2011), pp. 179-188
[6.]
R. Queiro, M. Alperi, S. Alonso, J.L. Riestra, J. Ballina.
Determinants of psoriatic arthritis in patients with psoriasis.
Expert Rev Dermatol, 5 (2010), pp. 67-77
[7.]
A.A. Saad, D.M. Ashcroft, K.D. Watson, K.L. Hyrich, P.R. Noyce, D.P. Symmons, British Society for Rheumatology Biologics Register.
Persistence with anti-tumour necrosis factor therapies in patients with psoriatic arthritis: observational study from the British Society of Rheumatology Biologics Register.
Arthritis Res Ther, 11 (2009), pp. R52
[8.]
R. Queiro Silva, S. Alonso Castro, J. Ballina García.
Biologic therapies different from the anti-TNF-α therapy in psoriasis and psoriatic arthritis.
Reumatol Clin, 6S1 (2010), pp. 41-46
[9.]
A. Gottlieb, A. Menter, A. Mendelsohn, Y.K. Shen, S. Li, C. Guzzo, et al.
Ustekinumab, a human interleukin 12/23 monoclonal antibody, for psoriatic arthritis: randomized, double-blind, placebo-controlled, crossover trial.
[10.]
A. Kavanaugh, A. Menter, A. Mendelsohn, Y.K. Shen, S. Lee, A.B. Gottlieb.
Effect of ustekinumab on physical function and healthrelated quality of life in patients with psoriatic arthritis: a randomized, placebo-controlled, phase II trial.
Curr Med Res Opin, 26 (2010), pp. 2385-2392
[11.]
Mendoza Jl, R. Lana, M. Díaz-Rubio.
Definiciones y manifestaciones clínicas generales.
Enfermedad Inflamatoria Intestinal, pp. 21-28
[12.]
A. Dignass, G. Van Assche, J.O. Lindsay, M. Lémann, J. Söderholm, J.F. Colombel, European Crohn's and Colitis Organisation (ECCO), et al.
The second European evidence-based consensus on the diagnosis and management of Crohn's disease: Current management.
J Crohns Colitis, 4 (2010), pp. 28-62
[13.]
S.B. Hanauer, B.G. Feagan, G.R. Lichtenstein, L.F. Mayer, S. Schreiber, J.F. Colombel, ACCENT I Study Group, et al.
Maintenance infliximab for Crohn's disease: the ACCENT I randomized trial.
Lancet, 359 (2002), pp. 1541-1549
[14.]
S.B. Hanauer, W.J. Sandborn, P. Rutgeerts, R.N. Fedorak, M. Lukas, D. MacIntosh, et al.
Human anti-tumor necrosis factor monoclonal antibody (adalimumab) in Crohn's disease: the CLASSIC-I trial.
Gastroenterology, 130 (2006), pp. 323-333
[15.]
J.F. Colombel, W.J. Sandborn, P. Rutgeerts, R. Enns, S.B. Hanauer, R. Panaccione, et al.
Adalimumab for maintenance of clinical response and remission in patients with Crohn's disease: the CHARM trial.
Gastroenterology, 132 (2007), pp. 52-65
[16.]
W.J. Sandborn, B.G. Feagan, S. Stoinov, P.J. Honiball, P. Rutgeerts, D. Mason, PRECISE 1 Study Investigators, et al.
Certolizumab pegol for the treatment of Crohn's disease.
N Engl J Med, 357 (2007), pp. 228-238
[17.]
I. Peluso, F. Pallone, G. Monteleone.
Interleukin-12 and Th1 immune response in Crohn's disease: pathogenetic relevance and therapeutic implication.
World J Gastroenterol, 12 (2006), pp. 5606-5610
[18.]
M.F. Neurath.
IL-23: a master regulator in Crohn's disease.
Nat Med, 13 (2007), pp. 26-28
[19.]
C.O. Elson, Y. Cong, C.T. Weaver, T.R. Schoeb, T.K. McClanahan, R.B. Fick, et al.
Monoclonal anti-interleukin 23 reverses active colitis in a T cell-mediated model in mice.
Gastroenterology, 132 (2007), pp. 2359-2370
[20.]
D. Yen, J. Cheung, H. Scheerens, F. Poulet, T. McClanahan, B. McKenzie, et al.
IL-23 is essential for T cell-mediated colitis and promotes inflammation via IL-17 and IL-6.
J Clin Invest, 116 (2006), pp. 1310-1316
[21.]
P.J. Mannon, I.J. Fuss, L. Mayer, C.O. Elson, W.J. Sandborn, D. Present, Anti-IL-12 Crohn's Disease Study Group, et al.
Anti-interleukin-12 antibody for active Crohn's disease.
N Engl J Med, 351 (2004), pp. 2069-2079
[22.]
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
[23.]
K.A. Papp, R.G. Langley, M. Lobwohl, 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
[24.]
W.J. Sandborn, B.G. Feagan, R.N. Fedorak, E. Scherl, M.R. Fleisher, S. Katz, Ustekinumab Crohn's Disease Study Group, et al.
A randomized trial of ustekinumab, a human interleukin-12/23 monoclonal antibody, in patients with moderate-to-severe Crohn's disease.
Gastroenterology, 135 (2008), pp. 1130-1141
[25.]
W.R. Best, J.M. Becktel, J.W. Singleton, F. Kern Jr., et al.
Development of a Crohn's disease activity index. National Cooperative Crohn's Disease Study.
Gastroenterology, 70 (1976), pp. 439-444
[26.]
E.J. Scherl, Kumar Sh, R.U. Warren.
Review of the safety and efficacy of ustekinumab.
Ther Adv Gastroenterol, 3 (2010), pp. 321-328
[27.]
G.P. Toedter, M. Blank, Y. Lang, D. Chen, W.J. Sandborn, W.J. de Villiers.
Relationship of C-reactive protein with clinical response after therapy with ustekinumab in Crohn's disease.
Am J Gastroenterol, 104 (2009), pp. 2768-2773
[28.]
C.L. Koelewijn, M.P. Schwartz, M. Samsom, B. Oldenburg.
C-reactive protein levels during a relapse of Crohn's disease are associated with the clinical course of the disease.
World J Gastroenterol, 14 (2008), pp. 85-89
[29.]
W. Sandborn, Gasink Ch, L. Gao, M. Blank, J. Johns, C. Guzzo, et al.
A Multicenter, Randomized, Double-blind. Placebo-Controlled Phase2b Study of Ustekinumab, a Human Monoclonal Antibody to IL-12/23p40, in Patients with Moderately to Severely Active Crohn's Disease: Results through Week 22 from the CERTIFI Trial.
Gastroenterology, 140 (2011), pp. s109
[30.]
G. Toedler, X. Wu, L. Gao, Ch. Gasink.
Reductions in Fecal Calprotectin and Lactoferrin Following Ustekinumab Induction Therapy in Patients with Moderate to Severe Crohn's Disease Who Have Previously Failed or Been Intolerant of TNF Antagonist Therapies.
Gastroenterology, 140 (2011), pp. s264
[31.]
J.P. Gisbert, Y. González-Lama, J. Maté.
Papel de los marcadores biológicos en la enfermedad inflamatoria intestinal.
Gastroenterol Hepatol, 30 (2007), pp. 117-129
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