EXTENDED REPORT

Risks of solid cancers in patients with rheumatoid arthritis and after treatment with tumour necrosis factor antagonists

J Askling^1,2, C M Fored¹, L Brandt¹, E Baecklund³, L Bertilsson⁴, N Feltelius^2,5, L Cöster⁶, P Geborek⁷, L T Jacobsson⁸, S Lindblad², J Lysholm⁹, S Rantapää-Dahlqvist¹⁰, T Saxne⁷, L Klareskog²

¹ Clinical Epidemiology Unit, Department of Medicine, Karolinska University Hospital, Stockholm, Sweden
² Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Stockholm, Sweden
³ Department of Rheumatology, Uppsala University Hospital, Uppsala, Sweden
⁴ Department of Rheumatology, Sahlgrenska University Hospital, Gothenburg, Sweden
⁵ Medical Products Agency, Uppsala, Sweden
⁶ Department of Rheumatology, Linköping University Hospital, Linköping, Sweden
⁷ Department of Rheumatology, Lund University Hospital, Lund, Sweden
⁸ Department of Rheumatology, Malmö University Hospital, Malmö, Sweden
⁹ Department of Rheumatology, Falu County Hospital, Falun, Sweden
¹⁰ Department of Rheumatology, University Hospital, Umeå, Sweden

Correspondence to:
Dr J Askling
Clinical Epidemiology Unit M9:01, Karolinska University Hospital Solna, SE-171 76 Stockholm, Sweden; johan.askling{at}medks.ki.se

Background: Existing studies of solid cancers in rheumatoid arthritis (RA) reflect cancer morbidity up until the early 1990s in prevalent cohorts admitted to hospital during the 1980s.

Objective: To depict the cancer pattern of contemporary patients with RA, from updated risk data from prevalent and incident RA populations. To understand the risk of solid cancer after tumour necrosis factor (TNF) treatment by obtaining cancer data from cohorts treated in routine care rather than trials.

Methods: A population based study of three RA cohorts (one prevalent, admitted to hospital 1990–2003 (n = 53 067), one incident, diagnosed 1995–2003 (n = 3703), and one treated with TNF antagonists 1999–2003 (n = 4160)), which were linked with Swedish nationwide cancer and census registers and followed up for cancer occurrence through 2003.

Results: With 3379 observed cancers, the prevalent RA cohort was at marginally increased overall risk of solid cancer, with 20–50% increased risks for smoke related cancers and +70% increased risk for non-melanoma skin cancer, but decreased risk for breast (–20%) and colorectal cancer (–25%). With 138 cancers, the incident RA cohort displayed a similar cancer pattern apart from non-decreased risks for colorectal cancer. TNF antagonist treated patients displayed solid cancer (n = 67) risks largely similar to those of other patients with RA.

Conclusion: The cancer pattern in patients treated with TNF antagonists mirrors those of other contemporary as well as historic RA cohorts. The consistent increase in smoking associated cancers in patients with RA emphasises the potential for smoking cessation as a cancer preventive measure in RA.

Abbreviations: NRN, national registration number; NSAID, non-steroidal anti-inflammatory drug; RA, rheumatoid arthritis; SIR, standardised incidence ratio; TNF, tumour necrosis factor

Keywords: cancer; risk; rheumatoid arthritis; epidemiology; Sweden; tumour necrosis factor

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Simon, T A, Smitten, A L, Franklin, J, Askling, J, Lacaille, D, Wolfe, F, Hochberg, M C, Qi, K, Suissa, S (2009). Malignancies in the rheumatoid arthritis abatacept clinical development programme: an epidemiological assessment. Ann Rheum Dis 68: 1819-1826 [Abstract] [Full Text]  
• Zink, A, Askling, J, Dixon, W G, Klareskog, L, Silman, A J, Symmons, D P M (2009). European biologicals registers: methodology, selected results and perspectives. Ann Rheum Dis 68: 1240-1246 [Abstract] [Full Text]  
• Leombruno, J P, Einarson, T R, Keystone, E C (2009). The safety of anti-tumour necrosis factor treatments in rheumatoid arthritis: meta and exposure-adjusted pooled analyses of serious adverse events. Ann Rheum Dis 68: 1136-1145 [Abstract] [Full Text]  
• Bongartz, T, Warren, F C, Mines, D, Matteson, E L, Abrams, K R, Sutton, A J (2009). Etanercept therapy in rheumatoid arthritis and the risk of malignancies: a systematic review and individual patient data meta-analysis of randomised controlled trials. Ann Rheum Dis 68: 1177-1183 [Abstract] [Full Text]  
• Fidder, H, Schnitzler, F, Ferrante, M, Noman, M, Katsanos, K, Segaert, S, Henckaerts, L, Van Assche, G, Vermeire, S, Rutgeerts, P (2009). Long-term safety of infliximab for the treatment of inflammatory bowel disease: a single-centre cohort study. Gut 58: 501-508 [Abstract] [Full Text]  
• Hemminki, K., Li, X., Sundquist, J., Sundquist, K. (2009). Cancer risks in Crohn disease patients. Ann Oncol 20: 574-580 [Abstract] [Full Text]  
• Furst, D E, Keystone, E C, Kirkham, B, Fleischmann, R, Mease, P, Breedveld, F C, Smolen, J S, Kalden, J R, Burmester, G R, Braun, J, Emery, P, Winthrop, K, Bresnihan, B, De Benedetti, F, Dorner, T, Gibofsky, A, Schiff, M H, Sieper, J, Singer, N, Van Riel, P L C M, Weinblatt, M E, Weisman, M H (2008). Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2008. Ann Rheum Dis 67: iii2-iii25 [Full Text]  
• Hemminki, K., Li, X., Sundquist, K., Sundquist, J. (2008). Cancer risk in hospitalized rheumatoid arthritis patients. Rheumatology (Oxford) 47: 698-701 [Abstract] [Full Text]  
• Boulton, J. G., Bax, D. E. (2008). An unusual cause of abnormal liver function in a patient with rheumatoid arthritis. Rheumatology (Oxford) 47: 226-227 [Full Text]  
• Furst, D E, Breedveld, F C, Kalden, J R, Smolen, J S, Burmester, G R, Sieper, J, Emery, P, Keystone, E C, Schiff, M H, Mease, P, van Riel, P L C M, Fleischmann, R, Weisman, M H, Weinblatt, M E (2007). Updated consensus statement on biological agents for the treatment of rheumatic diseases, 2007. Ann Rheum Dis 66: iii2-iii22 [Full Text]  
• Carmona, L., Descalzo, M. A., Perez-Pampin, E., Ruiz-Montesinos, D., Erra, A., Cobo, T., Gomez-Reino, J. J, on behalf of the BIOBADASER and EMECAR Groups, (2007). 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: 880-885 [Abstract] [Full Text]  
• Burmester, G. R, Mariette, X., Montecucco, C., Monteagudo-Saez, I., Malaise, M., Tzioufas, A. G, Bijlsma, J. W J, Unnebrink, K., Kary, S., Kupper, H., on behalf of the Research in Active Rheumatoid Art, (2007). Adalimumab alone and in combination with disease-modifying antirheumatic drugs for the treatment of rheumatoid arthritis in clinical practice: the Research in Active Rheumatoid Arthritis (ReAct) trial. Ann Rheum Dis 66: 732-739 [Abstract] [Full Text]  
• Corona, R., Bigby, M. (2007). What Are the Risks of Serious Infections and Malignancies for Patients Treated With Anti-Tumor Necrosis Factor Antibodies?. Arch Dermatol 143: 405-406 [Full Text]  
• Capell, H. A, Madhok, R., Porter, D. R, Munro, R. A L, McInnes, I. B, Hunter, J. A, Steven, M., Zoma, A., Morrison, E., Sambrook, M., Wui Poon, F., Hampson, R., McDonald, F., Tierney, A., Henderson, N., Ford, I. (2007). Combination therapy with sulfasalazine and methotrexate is more effective than either drug alone in patients with rheumatoid arthritis with a suboptimal response to sulfasalazine: results from the double-blind placebo-controlled MASCOT study. Ann Rheum Dis 66: 235-241 [Abstract] [Full Text]  
• Symmons, D. P. M. (2007). Lymphoma and rheumatoid arthritis--again. Rheumatology (Oxford) 46: 1-2 [Full Text]  
• Klareskog, L, Gaubitz, M, Rodriguez-Valverde, V, Malaise, M, Dougados, M, Wajdula, J, for The Etanercept Study 301 Investigators, (2006). A long-term, open-label trial of the safety and efficacy of etanercept (Enbrel) in patients with rheumatoid arthritis not treated with other disease-modifying antirheumatic drugs. Ann Rheum Dis 65: 1578-1584 [Abstract] [Full Text]  
• Pucino, F. Jr., Harbus, P. T., Goldbach-Mansky, R. (2006). Use of biologics in rheumatoid arthritis: Where are we going?. Am J Health Syst Pharm 63: S19-S41 [Abstract] [Full Text]  
• Scott, D.L., Kingsley, G.H. (2006). Tumor Necrosis Factor Inhibitors for Rheumatoid Arthritis.. NEJM 355: 704-712 [Full Text]  
• Askling, J, Fored, C M, Geborek, P, Jacobsson, L T H, van Vollenhoven, R, Feltelius, N, Lindblad, S, Klareskog, L (2006). Swedish registers to examine drug safety and clinical issues in RA. Ann Rheum Dis 65: 707-712 [Abstract] [Full Text]  
• Bongartz, T., Sutton, A. J., Sweeting, M. J., Buchan, I., Matteson, E. L., Montori, V. (2006). 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: 2275-2285 [Abstract] [Full Text]  
• Askling, J, Fored, C M, Baecklund, E, Brandt, L, Backlin, C, Ekbom, A, Sundstrom, C, Bertilsson, L, Coster, L, Geborek, P, Jacobsson, L T, Lindblad, S, Lysholm, J, Rantapaa-Dahlqvist, S, Saxne, T, Klareskog, L, Feltelius, N (2005). Haematopoietic malignancies in rheumatoid arthritis: lymphoma risk and characteristics after exposure to tumour necrosis factor antagonists. Ann Rheum Dis 64: 1414-1420 [Abstract] [Full Text]