Publique en esta revista
Información de la revista
Vol. 4. Núm. S2.
Monográfico: Infección y patologías microcristalinas
Páginas 18-23 (Octubre 2008)
Compartir
Compartir
Descargar PDF
Más opciones de artículo
Vol. 4. Núm. S2.
Monográfico: Infección y patologías microcristalinas
Páginas 18-23 (Octubre 2008)
Infección y patologías microcristalinas
Acceso a texto completo
Infecciones en pacientes con artritis reumatoide en tratamiento con fármacos anti-TNFα
Infections in Patients With Rheumatoid Arthritis Undergoing Anti-TNFα Drug Therapy
Visitas
...
Alberto Alonso Ruiz??
Autor para correspondencia
alonsoru@teleline.es

Correspondencia: Dr. A. Alonso Ruiz. Servicio de Reumatología. Hospital de Cruces. 48903 Baracaldo. Vizcaya. España.
Servicio de Reumatología. Hospital de Cruces. Baracaldo. Vizcaya. España
Información del artículo
Resumen
Bibliografía
Descargar PDF
Estadísticas

Las infecciones son más frecuentes en los pacientes afectos de artritis reumatoide (AR). La capacidad de los fármacos contra el factor de necrosis tumoral (TNF) (infliximab, etanercept y adalimumab) para aumentar el riesgo de infecciones ha sido motivo de discusión durante los últimos años. Sólo en dos de los ensayos clínicos que han permitido la comercialización del infliximab y del adalimumab, se observó una mayor incidencia de infecciones graves. No se observó mayor incidencia de tuberculosis (TB) en los ensayos. Sin embargo, más tarde se han publicado estudios no controlados que muestran mayor incidencia de infecciones y de TB en pacientes con AR que reciben anti-TNFα. La discordancia entre los ensayos clínicos iniciales y los estudios no controlados posteriores ha sido el motivo de la realización de metaanálisis que estudian la frecuencia de infecciones en pacientes con AR que reciben fármacos anti-TNFα. Los tres metaanálisis publicados muestran un incremento del riesgo de infecciones en los pacientes con AR en tratamiento con infliximab y con adalimumab, especialmente cuando se administran dosis altas. El riesgo no parece estar aumentado con etanercept, probablemente debido a que no se han utilizado dosis superiores a las recomendadas en los ensayos analizados. El aumento en el riesgo de infecciones no fue detectado en los ensayos clínicos, pero el metaanálisis aumenta la potencia estadística y permite demostrar el incremento del riesgo de infecciones. Existe una relación causal entre la administración de fármacos anti-TNFα y el desarrollo de infecciones que cumple todos los criterios de causalidad.

Palabras clave:
Artritis reumatoide
Anti-TNFα
Infección

Infections are more frequent in patients with rheumatoid arthritis (RA). The capacity of the anti-TNF drugs (infliximab, etanercept, and adalimumab) to increase the risk of infections has been a motive of discussion during the past years. Only in two of the trials that have allowed the marketing of the infliximab and adalimumab more serious infections were observed. TB was not observed in the trials. Nevertheless, later they have been published not controlled studies that show infections and TB in patients with RA that receive anti-TNFα drugs. The disagreement between the trials and the not controlled studies has been the motive of the accomplishment of metaanalysis which study the frequency of infections in patients with RA that receive anti-TNFα drugs. The three metaanalysis published show an increase of the risk of infections in patients with AR in treatment with infliximab and with adalimumab, specially when they administer high doses. This risk does not seem to increase with etanercept, probably due to the fact that doses superior to the recommended ones have not been used in the analyzed trials. Increased risk of infections was not detected in the trials, but the metaanalysis increases the statistical power and allow demonstrating increased risk of infections. A causal relation exists between the administration of anti-TNFα and the development of infections, fulfilling all the criteria of causality.

Key words:
Rheumatoid arthritis
Anti-TNFα
Infection
El Texto completo está disponible en PDF
Bibliografía
[1.]
M.F. Doran, C.S. Crowson, G.R. Pond, W.M. O’Fallon, S.E. Gabriel.
Frequency of infection in patients with rheumatoid arthritis compared with controls: a population-based study.
Arthritis Rheum, 46 (2002), pp. 2287-2293
[2.]
M.F. Doran, C.S. Crowson, G.R. Pond, W.M. O’Fallon, S.E. Gabriel.
Predictors of infection in rheumatoid arthritis.
Arthritis Rheum, 46 (2002), pp. 2294-2300
[3.]
S. Bernatsky, M. Hudson, S. Suissa.
Anti-rheumatic drug use and risk of serious infections in rheumatoid arthritis.
Rheumatology, 46 (2007), pp. 1157-1160
[4.]
P.E. Lipsky, D.M. Van der Heijde, E.W. St. Clair, D.E. Furst, F.C. Breedveld, J.R. Kalden, et al.
Infliximab and methotrexate in the treatment of rheumatoid arthritis. Anti-Tumor Necrosis Factor Trial in Rheumatoid Arthritis with Concomitant Therapy Study Group.
N Engl J Med, 343 (2000), pp. 1595-1602
[5.]
E.W. St. Clair, D.M. Van der Heijde, J. Smolen, R.N. Maini, J.M. Bathon, P. Emery, et al.
Combination of infliximab and methotrexate therapy for early rheumatoid arthritis. A randomized, controlled trial.
Arthritis Rheum, 50 (2004), pp. 3432-3443
[6.]
R. Westhovens, D. Yocum, J. Han, A. Berman, I. Strusberg, P. Geusens, et al.
The safety of infliximab, combined with background treatments, among patients with rheumatoid arthritis and various comorbidities. A large, randomized, placebo-controlled trial.
Arthritis Rheum, 54 (2006), pp. 1075-1086
[7.]
L.W. Moreland, M.H. Schiff, S.W. Baumgartner, E.A. Tindall, R.M. Fleischmann, K.J. Bulpitt, et al.
Etanercept therapy in rheumatoid arthritis. A randomized, controlled trial.
Ann Intern Med, 130 (1999), pp. 478-486
[8.]
M.E. Weinblatt, J.M. Kremer, A.D. Bankhurst, K.J. Bulpitt, R.M. Fleischmann, R.I. Fox, et al.
A trial of etanercept, a recombinant tumor necrosis factor receptor: Fc fusion protein, in patients with rheumatoid arthritis receiving methotrexate.
N Engl J Med, 340 (1999), pp. 253-259
[9.]
J.M. Bathon, R.W. Martin, R.M. Fleischmann, J.R. Tesser, M.H. Schiff, E.C. Keystone.
A comparison of etanercept and methotrexate in patients with early rheumatoid arthritis.
N Engl J Med, 343 (2000), pp. 1586-1593
[10.]
D. Van der Heijde, L. Klareskog, V. Rodríguez-Valverde, C. Codreanu, H. Bolosiu, J. Melo-Gomes, For the TEMPO study investigators, et al.
Comparison of etanercept and methotrexate, alone and combined, in the treatment of rheumatoid arthritis. Two-year clinical and radiographic results from the TEMPO study, a double-blind, randomized trial.
Arthritis Rheum, 54 (2006), pp. 1063-1074
[11.]
M.E. Weinblatt, E.C. Keystone, D.E. Furst, L.W. Moreland, M.H. Weisman, C.A. Birbara, et al.
Adalimumab, a fully human anti-tumor necrosis factor alpha monoclonal antibody, for the treatment of rheumatoid arthritis in patients taking concomitant methotrexate: the ARMADA trial.
Arthritis Rheum, 48 (2003), pp. 35-45
[12.]
L.B.A. Van de Putte, C. Atkins, M. Malaise, J. Sany, A.S. Russell, P.L.C.M. Van Riel, et al.
Efficacy and safety of adalimumab as monotherapy in patients with rheumatoid arthritis for whom previous disease modifying antirheumatic drug treatment has failed.
Ann Rheum Dis, 63 (2004), pp. 508-516
[13.]
D.E. Furst, M.H. Schiff, R.M. Fleischmann, V. Strand, C.A. Birbara, D. Compagnone, et al.
Adalimumab, a fully human anti-tumor necrosis factoralfa monoclonal antibody, and concomitant standard antirheumatic therapy for the treatment of rheumatoid arthritis: results of STAR (Safety Trial of Adalimumab in Rheumatoid Arthritis).
J Rheumatol, 30 (2003), pp. 2563-2571
[14.]
E.C. Keystone, Kavanaugh, J.T. Sharp, H. Tannenbaum, Y. Hua, L.S. Teoh, et al.
Radiographic, clinical, and functional outcomes of treatment with adalimumab (a human anti-tumor necrosis factor monoclonal antibody) in patients with active rheumatoid arthritis receiving concomitant methotrexate therapy. A randomized, placebo-controlled, 52-week trial.
Arthritis Rheum, 50 (2004), pp. 1400-1411
[15.]
F.C. Breedveld, M.H. Weisman, A.F. Kavanaugh, S.B. Cohen, K. Pavelka, R. Van Vollenhoven, The PREMIER study, et al.
A multicenter, randomized, double-blind clinical trial of combination therapy with adalimumab plus methotrexate versus methotrexate alone or adalimumab alone in patients with early, aggressive rheumatoid arthritis who had not had previous methotrexate treatment.
Arthritis Rheum, 54 (2006), pp. 26-37
[16.]
S. Kroesen, A.F. Widmer, A. Tyndall, P. Hasler.
Serious bacterial infections in patients with rheumatoid arthritis under anti-TNF-alpha therapy.
Rheumatology (Oxford), 42 (2003), pp. 617-621
[17.]
J. Listing, A. Strangfeld, S. Kary, R. Rau, U. Von Hinueber, M. Stoyanova-Scholz, et al.
Infections in patients with rheumatoid arthritis treated with biologic agents.
Arthritis Rheum, 52 (2005), pp. 3403-3412
[18.]
J.J. Gomez-Reino, L. Carmona, V.R. Valverde, E.M. Mola, M.D. Montero.
Treatment of rheumatoid arthritis with tumor necrosis factor inhibitors may predispose to significant increase in tuberculosis risk: a multicenter active-surveillance report.
Arthritis Rheum, 48 (2003), pp. 2122-2127
[19.]
L. Carmona, J.J. Gomez-Reino, V. Rodriguez-Valverde, D. Montero, E. Pascual-Gomez, E.M. Mola, et al.
Effectiveness of recommendations to prevent reactivation of latent tuberculosis infection in patients treated with tumor necrosis factor antagonists.
Arthritis Rheum, 52 (2005), pp. 1766-1772
[20.]
R.S. Wallis, M.S. Broder, J.Y. Wong, M.E. Hanson, D.O. Beenhouwer.
Granulomatous infectious diseases associated with tumor necrosis factor antagonists.
Clin Infect Dis, 38 (2004), pp. 1261-1265
[21.]
T. Bongartz, A.J. Sutton, M.J. Sweeting, I. Buchan, E.L. Matteson, V. Montori.
Anti-TNF antibody therapy in rheumatoid arthritis and the risk of serious infections and malignancies: systematic review and meta-analysis of rare harmful effects in randomized controlled trials.
JAMA, 295 (2006), pp. 2275-2285
[22.]
Y.F. Chen, P. Jobanputra, P. Barton, S. Jowett, S. Bryan, W. Clark, et al.
A systematic review of the effectiveness of adalimumab, etanercept and infliximab for the treatment of rheumatoid arthritis in adults and an economic evaluation of their cost-effectiveness.
Health Technol Assess, 10 (2006), pp. 1-248
[23.]
A. Alonso-Ruiz, J.I. Pijoan, E. Ansuategui, A. Urkaregi, M. Calabozo, A. Quintana.
Anti-tumor necrosis factor alpha drugs in rheumatoid arthritis: systematic review and metaanalysis of efficacy and safety.
BMC Musculoskeletal Disorders, 9 (2008), pp. 52
[24.]
W. Dixon, A. Silman.
Is there an association between anti-TNF monoclonal antibody therapy in rheumatoid arthritis and risk of malignancy and serious infection? Commentary on meta-analysis by Bongartz et al.
Arthritis Res Ther, 8 (2008), pp. 111-113
[25.]
M. Delgado.
Causalidad.
Fundamentos de Diseño y Estadística. UD 7. Investigación científica: diseño de estudios, pp. 23-53

Esta revisión ha sido presentada en el I Simposio de infección y patologías microcristalinas, de la Sociedad Española de Reumatología (SER) (Cádiz, 8 de marzo de 2008).

Copyright © 2008. Elsevier España S.L. Barcelona
Idiomas
Reumatología Clínica

Suscríbase a la newsletter

Opciones de artículo
Herramientas
es en

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?