Ustekinumab. Análisis de efectos adversos infecciosos

Herranz-Pinto, P.; Sendagorta, E.

doi:10.1016/S0001-7310(12)70005-4

Información del artículo

Resumen

Ustekinumab es el primer representante de un nuevo grupo de fármacos biológicos, cuyo mecanismo de acción principal es la inhibición selectiva de la actividad de las interleucinas 12 y 23. A pesar de ser la terapia de uso más reciente en dermatología, es el fármaco que mayor número de pacientes ha aportado en su desarrollo clínico en psoriasis. Gracias a esta experiencia acumulada, se ha confirmado que el perfil de seguridad de ustekinumab frente a eventos infecciosos demuestra un riesgo similar a placebo y equiparable a la población general en cuanto a incidencia absoluta, infecciones severas y requerimientos de antibioterapia adicional. Este comportamiento inicial se confirma durante el seguimiento a 3 y 4 años en pacientes con psoriasis moderada a severa.

A pesar de este perfil favorable de seguridad, el carácter inmunosupresor selectivo de ustekinumab aconseja mantener un seguimiento estricto de los pacientes en tratamiento, como el despistaje de infecciones activas o latentes, similar a los aplicados en el caso de los fármacos anti factor de necrosis tumoral.

Palabras clave:

Ustekinumab

Psoriasis

Efectos adversos

Seguridad

Infecciones

Abstract

Ustekinumab is the first of a new class of biologic agents whose main mechanism of action involves the selective inhibition of IL-12 and IL-23. Although ustekinumab is the latest biologic to be approved for use in dermatology, its approval was based on the largest clinical development program conducted to date in psoriasis. Safety data accumulated during the clinical development phase showed the risk of infection to be similar in patients in the ustekinumab and placebo groups. The use of additional antibiotics and the rates of overall infection and serious infection in patients on ustekinumab and the general population were also comparable. Subsequent studies confirmed the safety of this drug in patients with moderate to severe psoriasis treated for 3 or 4 years. Despite its favorable safety profile, ustekinumab is a selective immunosuppressant. Clinicians should therefore closely monitor patients and apply screening measures similar to those used during anti-TNF therapy to detect de novo infections or the reactivation of latent infections.

Keywords:

Ustekinumab

Psoriasis

Adverse effects

Safety

Infections

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References

[1.]

F.O. Nestle, D.H. Kaplan, J. Barker.

Psoriasis.

N Engl J Med, 361 (2009), pp. 496-509

http://dx.doi.org/10.1056/NEJMra0804595 | Medline

[2.]

M. Lebwohl.

New developments in the treatment of psoriasis.

Arch Dermatol., 138 (2002), pp. 686-688

Medline

[3.]

A. Di Cesare, P. Di Meglio, F.O. Nestle.

The IL-23/Th17 axis in the immunopathogenesis of psoriasis.

J Invest Dermatol, 129 (2009), pp. 1339-1350

http://dx.doi.org/10.1038/jid.2009.59 | 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.]

J.V. Scanlon, B.P. Exter, M. Steinberg, C.I. Jarvis.

Ustekinumab: treatment of adult moderate-to-severe chronic plaque psoriasis.

Ann Pharmacother, 43 (2009), pp. 1456-1465

http://dx.doi.org/10.1345/aph.1M151 | Medline

[7.]

Leonardi C GL, Wasel N, Yeilding N, Szapary P, Hsu MC, Langley R, et al. Characterization of infections associated with ustekinumab in moderate to severe psoriasis patients. PO49. Psoriasis 2010, Congress of the International Psoriasis Network. Paris, 1–4 Jul 2010.

[8.]

Gordon K LC, Griffiths CEM, Szapary P, Yeilding N, Hsu MC, Wasel N, et al. Ustekinumab safety update: cumulative experience from longer term follow-up of patients treated in the ustekinumab psoriasis clinical development program. Psoriasis 2010, Congress of the International Psoriasis Network. París, 1–4 Jul 2010. Poster 047.

[9.]

Reich K LC, Griffiths CEM, Szapary PO, Wasfi Y, Hsu MC, Gordon K on behalf of the PHOENIX 1 & 2 and ACCEPT investigators. Update on the cumulative safety experience of ustekinumab: results from the ustekinumab psoriasis clinical development program with up to 4 years of follow-up. FC07-03 World Congress of Dermatology. Seúl, Corea, 2011.

[10.]

G. Trinchieri, S. Pflanz, R.A. Kastelein.

The IL-12 family of heterodimeric cytokines: new players in the regulation of T cell responses.

Immunity, 19 (2003), pp. 641-644

Medline

[11.]

O. Filipe-Santos, J. Bustamante, A. Chapgier, G. Vogt, L. De Beaucoudrey, J. Feinberg, et al.

Inborn errors of IL-12/23- and IFN-gamma-mediated immunity: molecular, cellular, and clinical features.

Semin Immunol, 18 (2006), pp. 347-361

http://dx.doi.org/10.1016/j.smim.2006.07.010 | Medline

[12.]

J.L. Casanova, L. Abel.

Genetic dissection of immunity to mycobacteria: the human model.

Annu Rev Immunol, 20 (2002), pp. 581-620

http://dx.doi.org/10.1146/annurev.immunol.20.081501.125851 | Medline

[13.]

C. Fieschi, J.L. Casanova.

The role of interleukin-12 in human infectious diseases: only a faint signature.

Eur J Immunol, 33 (2003), pp. 1461-1464

http://dx.doi.org/10.1002/eji.200324038 | Medline

[14.]

C. MacLennan, C. Fieschi, D.A. Lammas, C. Picard, S.E. Dorman, O. Sanal, et al.

Interleukin (IL)-12 and IL-23 are key cytokines for immunity against Salmonella in humans.

J Infect Dis, 190 (2004), pp. 1755-1757

http://dx.doi.org/10.1086/425021 | Medline

[15.]

L. De Beaucoudrey, A. Samarina, J. Bustamante, A. Cobat, S. Boisson- Dupuis, J. Feinberg, et al.

Revisiting human IL-12Rβ1 deficiency: a survey of 141 patients from 30 countries.

Medicine (Baltimore), 89 (2010), pp. 381-402

[16.]

Herranz-Pinto P S-CE, Casado-Verrier B, Gómez-Fernández C, Alonso-Pacheco ML, Casado-Jiménez ML. Psoriasis en pacientes con coinfección VIH-VHC. Primer año de tratamiento con ustekinumab. Póster Congreso Nacional de Dermatología 2011. Santiago de Compostela, 2011.

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