Información del artículo
Abstract
Tumor necrosis factor (TNF) is implicated in the control of tumoral growth in addition to the systemic inflammatory response. TNF blockage produces a comprensible reservation in patients with risk factors for cancer. No clear evidence for this came out from pre-clinical or clinical trials. Biosafety registries established in the post-marketing phase have concluded that, in general, cancer cases have not increased over what is expected in a population with RA exposed to the prolongued use of anti-TNF drugs. A meta-analysis of clinical trials which used infliximab and adalimumab for RA treatment showed an increase of up to three times the risk of developing cancer, but this dissapeared after correcting for time. Biobadaser shows evidence that support long-term safety. In the long-term, and if the inflammatory disease activity is truly under control, the risk of developing cancer is the same as with any other patient.
Keywords:
Infliximab
Etanercept
Adalimumab
Cancer
Adverse event
Resumen
El factor de necrosis tumoral (TNF) está implicado en el control del crecimiento de tumores además de en la respuesta inflamatoria sistémica. El bloqueo del TNF produce un recelo comprensible en pacientes con riesgo de cáncer. Ni en el desarrollo preclínico ni durante los ensayos clínicos de los anti-TNF se detectaron alarmas claras. Los registros de seguridad de biológicos establecidos en el período poscomercialización han concluido que el cáncer en general no está aumentado con respecto de lo esperado en una población de AR con el uso prolongado de anti-TNF. Un meta-análisis de ensayos clínicos de infliximab y adalimumab mostró un aumento de hasta tres veces el riesgo de cáncer, pero al corregir la exposición por el tiempo en los mismos no se encontró. En BIOBADASER tenemos evidencias que apoyan la seguridad a largo plazo. A largo plazo, y si realmente la actividad inflamatoria de la enfermedad subyacente está controlada, el riesgo de desarrollar un cáncer es igual que el de cualquier paciente.
Palabras clave:
Infliximab
Etanercept
Adalimumab
Cáncer
Efecto adverso
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References
[1.]
B.B. Aggarwal, T.E. Eessalu, P.E. Hass.
Characterization of receptors for human tumour necrosis factor and their regulation by gamma-interferon.
Nature, 318 (1985-1986), pp. 665-667
[2.]
A. Okubo, S. Sone, S.M. Singh, T. Ogura.
Production of tumor necrosis factor-alpha by alveolar macrophages of lung cancer patients.
Jpn J Cancer Res, 81 (1990), pp. 403-409
[3.]
P. Ghezzi, A. Cerami.
Tumor necrosis factor as a pharmacological target.
Mol Biotechnol, 31 (2005), pp. 239-244
[4.]
J. Gelin, L.L. Moldawer, C. Lonnroth, B. Sherry, R. Chizzonite, K. Lundholm.
Role of endogenous tumor necrosis factor alpha and interleukin 1 for experimental tumor growth and the development of cancer cachexia.
Cancer Res, 51 (1991), pp. 415-421
[5.]
T. Kiyama, M. Onda, A. Tokunaga, I. Fujita, T. Okuda, T. Mizutani, et al.
The presence of tumor necrosis factor-alpha and its antibody in the sera of cachexic patients with gastrointestinal cancer.
Surg Today, 24 (1994), pp. 759-762
[6.]
G.M. Williams.
Antitumor necrosis factor-alpha therapy and potential cancer inhibition.
Eur J Cancer Prev, 17 (2008), pp. 169-177
[7.]
S. Madhusudan, M. Foster, S.R. Muthuramalingam, J.P. Braybrooke, S. Wilner, K. Kaur, et al.
A phase II study of etanercept (Enbrel), a tumor necrosis factor alpha inhibitor in patients with metastatic breast cancer.
Clin Cancer Res, 10 (2004), pp. 6528-6534
[8.]
S. Madhusudan, S.R. Muthuramalingam, J.P. Braybrooke, S. Wilner, K. Kaur, C. Han, et al.
Study of etanercept, a tumor necrosis factor-alpha inhibitor, in recurrent ovarian cancer.
J Clin Oncol, 23 (2005), pp. 5950-5959
[9.]
E.R. Brown, K.A. Charles, S.A. Hoare, R.L. Rye, D.I. Jodrell, R.E. Aird, et al.
A clinical study assessing the tolerability and biological effects of infliximab, a TNF-alpha inhibitor, in patients with advanced cancer.
Ann Oncol, 19 (2008), pp. 1340-1346
[10.]
J. Friedberg, E. Jacobsen, D. Neuberg, J. Kutok, O. Munoz, V. Boussiotis, et al.
Targeting the follicular lymphoma microenvironment through blockade of TNFalpha with etanercept.
Leuk Lymphoma, 49 (2008), pp. 902-909
[11.]
A. Jatoi, S.R. Dakhil, P.L. Nguyen, J.A. Sloan, J.W. Kugler, K.M. Rowland, et al.
A placebocontrolled double blind trial of etanercept for the cancer anorexia/weight loss syndrome: results from N00C1 from the North Central Cancer Treatment Group.
Cancer, 110 (2007), pp. 1396-1403
[12.]
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
[13.]
J.P. Leombruno, T.R. Einarson, E.C. Keystone.
The safety of anti-Tumor Necrosis Factor treatments in rheumatoid arthritis: meta and exposure adjusted pooled analyses of serious adverse events.
Ann Rheum Dis, (2008),
[14.]
S.L. Brown, M.H. Greene, S.K. Gershon, E.T. Edwards, M.M. Braun.
Tumor necrosis factor antagonist therapy and lymphoma development: twenty-six cases reported to the Food and Drug Administration.
Arthritis Rheum, 46 (2002), pp. 3151-3158
[15.]
P. Geborek, A. Bladstrom, C. Turesson, A. Gulfe, I.F. Petersson, T. Saxne, et al.
Tumour necrosis factor blockers do not increase overall tumour risk in patients with rheumatoid arthritis, but may be associated with an increased risk of lymphomas.
Ann Rheum Dis, 64 (2005), pp. 699-703
[16.]
J. Askling, C.M. Fored, E. Baecklund, L. Brandt, C. Backlin, A. Ekbom, et al.
Haematopoietic malignancies in rheumatoid arthritis: lymphoma risk and characteristics after exposure to tumour necrosis factor antagonists.
Ann Rheum Dis, 64 (2005), pp. 1414-1420
[17.]
F. Wolfe, K. Michaud.
Lymphoma in rheumatoid arthritis: the effect of methotrexate and anti-tumor necrosis factor therapy in 18,572 patients.
Arthritis Rheum, 50 (2004), pp. 1740-1751
[18.]
F. Wolfe, K. Michaud.
The effect of methotrexate and anti-tumor necrosis factor therapy on the risk of lymphoma in rheumatoid arthritis in 19,562 patients during 89,710 person-years of observation.
Arthritis Rheum, 56 (2007), pp. 1433-1439
[19.]
E. Baecklund, A. Iliadou, J. Askling, A. Ekbom, C. Backlin, F. Granath, et al.
Association of chronic inflammation, not its treatment, with increased lymphoma risk in rheumatoid arthritis.
Arthritis Rheum, 54 (2006), pp. 692-701
[20.]
S. Setoguchi, D.H. Solomon, M.E. Weinblatt, J.N. Katz, J. Avorn, R.J. Glynn, et al.
Tumor necrosis factor alpha antagonist use and cancer in patients with rheumatoid arthritis.
Arthritis Rheum, 54 (2006), pp. 2757-2764
[21.]
L. Abasolo, L. Carmona, J.J. Gómez Reino, BIOBADASER Study Group.
Is The Exposure To TNF Antagonists A Risk Factor For Cancer In Rheumatoid Arthritis? ACR/AHRP.
Anual Scientific Meeting,
[22.]
L. Abasolo, L. Carmona, J.J. Gómez Reino, BIOBADASER Study Group.
Is The Incidence Risk Of Cancer Constant Through Time In Rheumatoid Arthritis Patients Exposed to Biologics?.
ACR/AHRP Anual Scientific Meeting,
[23.]
L. Carmona, M.A. Descalzo, E. Perez Pampin, D. Ruiz Montesinos, A. Erra, T. Cobo, et al.
All-cause and cause-specific mortality in rheumatoid arthritis are not greater than expected when treated with tumour necrosis factor antagonists.
Ann Rheum Dis, 66 (2007), pp. 880-885
[24.]
E. Szekanecz, C. Andras, Z. Sandor, P. Antal-Szalmas, J. Szanto, L. Tamasi, et al.
Malignancies and soluble tumor antigens in rheumatic diseases.
Autoimmun Rev, 6 (2006), pp. 42-47
[25.]
L. Abasolo, E. Judez, M.A. Descalzo, I. Gonzalez Alvaro, J.A. Jover, L. Carmona.
Cancer in rheumatoid arthritis: occurrence, mortality, and associated factors in a South European population.
Semin Arthritis Rheum, 37 (2008), pp. 388-397
[26.]
J. Askling, C.M. Fored, L. Brandt, E. Baecklund, L. Bertilsson, N. Feltelius, et al.
Risks of solid cancers in patients with rheumatoid arthritis and after treatment with tumour necrosis factor antagonists.
Ann Rheum Dis, 64 (2005), pp. 1421-1426
[27.]
M. Drini, P.J. Prichard, G.J. Brown, F.A. Macrae.
Hepatosplenic T-cell lymphoma following infliximab therapy for Crohn's disease.
Med J Aust, 189 (2008), pp. 464-465
[28.]
A.C. Mackey, L. Green, L.C. Liang, P. Dinndorf, M. Avigan.
Hepatosplenic T cell lymphoma associated with infliximab use in young patients treated for inflammatory bowel disease.
J Pediatr Gastroenterol Nutr, 44 (2007), pp. 265-267
[29.]
A. Zeidan, R. Sham, J. Shapiro, A. Baratta, P. Kouides.
Hepatosplenic T-cell lymphoma in a patient with Crohn's disease who received infliximab therapy.
Leuk Lymphoma, 48 (2007), pp. 1410-1413
[30.]
C. Nakashima, M. Tanioka, K. Takahashi, Y. Miyachi.
Diffuse large B-cell lymphoma in a patient with rheumatoid arthritis treated with infliximab and methotrexate.
Clin Exp Dermatol, 33 (2008), pp. 437-439
[31.]
P.D. Ziakas, S. Giannouli, A.G. Tzioufas, M. Voulgarelis.
Lymphoma development in a patient receiving anti-TNF therapy.
Haematologica, 88 (2003), pp. ECR25
[32.]
S.W. Smale, T.M. Lawson.
Monoclonal gammopathy of undetermined significance and anti-TNF-alpha treatment.
Scand J Rheumatol, 36 (2007), pp. 405-406
[33.]
C.W. Lees, J. Ironside, W.A. Wallace, J. Satsangi.
Resolution of non-small-cell lung cancer after withdrawal of anti-TNF therapy.
N Engl J Med, 359 (2008), pp. 320-321
[34.]
J. Sheppard, K. Raza, C.D. Buckley.
Skin cancer in psoriatic arthritis treated with anti- TNF therapy.
Rheumatology (Oxford), 46 (2007), pp. 1622-1623
[35.]
V.F. Manfredsdottir, T. Vikingsdottir, T. Jonsson, A.J. Geirsson, O. Kjartansson, M. Heimisdottir, et al.
The effects of tobacco smoking and rheumatoid factor seropositivity on disease activity and joint damage in early rheumatoid arthritis.
Rheumatology (Oxford), 45 (2006), pp. 734-740
[36.]
K. Aksu, A. Donmez, Y. Ertan, G. Keser, V. Inal, G. Oder, et al.
Hodgkin's lymphoma following treatment with etanercept in ankylosing spondylitis.
Rheumatol Int, 28 (2007), pp. 185-187
[37.]
J. Askling, L. Klareskog, P. Blomqvist, M. Fored, N. Feltelius.
Risk for malignant lymphoma in ankylosing spondylitis: a nationwide Swedish case-control study.
Ann Rheum Dis, 65 (2006), pp. 1184-1187
[38.]
E. Burstein, E.R. Fearon.
Colitis and cancer: a tale of inflammatory cells and their cytokines.
J Clin Invest, 118 (2008), pp. 464-467
[39.]
J. Askling, L. Brandt, A. Lapidus, P. Karlen, M. Bjorkholm, R. Lofberg, et al.
Risk of haematopoietic cancer in patients with inflammatory bowel disease.
Gut, 54 (2005), pp. 617-622
[40.]
R.A. Van Hogezand, R.F. Eichhorn, A. Choudry, R.A. Veenendaal, C.B. Lamers.
Malignancies in inflammatory bowel disease: fact or fiction?.
Scand J Gastroenterol Suppl, (2002), pp. 48-53
[41.]
S.J. Bickston, G.R. Lichtenstein, K.O. Arseneau, R.B. Cohen, F. Cominelli.
The relationship between infliximab treatment and lymphoma in Crohn's disease.
Gastroenterology, 117 (1999), pp. 1433-1437
[42.]
E. Roddy, P.A. Courtney, A. Morris.
Non-Hodgkin's lymphoma in a patient with refractory dermatomyositis which had been treated with infliximab.
Rheumatology (Oxford), 41 (2002), pp. 1194-1195
[43.]
K.E. Smedby, H. Hjalgrim, J. Askling, E.T. Chang, H. Gregersen, A. Porwit-MacDonald, et al.
Autoimmune and chronic inflammatory disorders and risk of non-Hodgkin lymphoma by subtype.
J Natl Cancer Inst, 98 (2006), pp. 51-60
[44.]
A. Knight, J. Askling, A. Ekbom.
Cancer incidence in a population-based cohort of patients with Wegener's granulomatosis.
Int J Cancer, 100 (2002), pp. 82-85
[45.]
J.H. Stone, J.T. Holbrook, M.A. Marriott, A.K. Tibbs, L.P. Sejismundo, Y.I. Min, et al.
Solid malignancies among patients in the Wegener's Granulomatosis Etanercept Trial.
Arthritis Rheum, 54 (2006), pp. 1608-1618
[46.]
Sociedad Española de Reumatología. Guía de Práctica Clínica para el Manejo de la Artritis reumatoide. 2007 cited. Available from: http://www.ser.es/practicaClinica/GUIPCAR_2007/Seguridad/Menu6_Seguridad_Anti-TNFs_VI2.php
[47.]
D.E. Furst, F.C. Breedveld, J.R. Kalden, J.S. Smolen, G.R. Burmester, J. Sieper, et al.
Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2007.
Ann Rheum Dis, 66 (2007), pp. iii2-iii22
[48.]
W.G. Dixon, K.D. Watson, M. Lunt, K.L. Hyrich, D.P.M. Symmons, BSRBR Control Centre Consortium, et al.
The Influence of Anti-TNF Therapy upon Cancer Incidence in Patients with Rheumatoid Arthritis (RA) who have had Prior Malignancy: Results from the BSRBR.
ACR/AHRP Anual Scientific Meeting,
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