Rheumatology Advance Access originally published online on February 23, 2008
Rheumatology 2008 47(4):548-549; doi:10.1093/rheumatology/ken026
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LETTERS TO THE EDITOR |
Risk of cancer in Turkish patients after treatment with TNF antagonists
GATA, Romatoloji BD, 06118 Etlik, Ankara, Turkey
Correspondence to: S. PAY, GATA Romatoloji BD, 06118 Etlik, Ankara, Turkey. E-mail: salihp{at}yahoo.com
SIR, There is conflicting evidence whether anti-TNF therapy offers an increased cancer risk in rheumatological disorders. In this study, we aimed to collect pilot data on a possible association between anti-TNF agent use and development of neoplasms among Turkish patients with various rheumatological conditions.
We conducted a nationwide survey pooling reported cases from 26 different rheumatology centers in Turkey. A total of 2199 patients (1247 females, 952 males, mean age: 41.8 ± 13.9 yrs) were reported. Among those patients, 943 had AS (1027.16 patient-years) (mean age: 37.3 ± 10.9 yrs), 931 RA (1145.14 patient-years) (mean age: 49.1 ± 12.7 yrs), 132 PsA (mean age: 43.6 ± 12.5 yrs), 127 JCA (mean age: 23.8 ± 10.9 yrs) and 66 other disorders (62.14 patient-years) (mean age: 30.9 ± 10.3 yrs). Nine-hundred and twenty-three patients had been treated with etanercept (1028.54 patient-years), 853 with infliximab (1014.68 patient-years) and 259 with adalimumab (223.69 patient-years). One-hundred and sixty-four patients had been treated with more than one anti-TNF agent. We used standardized incidence ratios (SIRs) as measures of relative risk were expected number were taken from a regional cancer survey conducted in the Izmir (Western Turkey) region.
Fifteen malignancies (13 solid cancers and 2 lymphoproliferative disorders) were observed (SIR = 1.26, 95% CI 0.70, 2.08). Ten patients had been treated with etanercept (SIR = 2.3, 95% CI 1.10, 4.23), three with infliximab (SIR = 0.66, 95% CI 0.14, 1.92), one with adalimumab (SIR = 0.62, 95% CI 0.02, 3.48) and one with etanercept and then adalimumab. Eleven RA patients (SIR = 1.36, 95% CI 0.68, 2.43), two AS patients (SIR = 0.66, 95% CI 0.08, 2.38) and two patients with other indications developed cancer after anti-TNF agents. Among RA patients who developed cancer, seven patients had been treated with etanercept (SIR = 2.46, 95% CI 0.99, 5.06), two with infliximab (SIR = 0.64, 95% CI 0.02, 3.56), one with adalimumab (SIR = 0.75, 95% CI 0.09, 2.72) and one with etanercept, and then switched to adalimumab (Fig. 1).
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The number of studies investigating a possible association between the use of TNF alpha antagonists in RA patients and the development of cancer have been published with inconclusive results. Wolfe and Michaud [1] reported increased risk of lymphoma in RA patients compared with the general population, and the risk was greatest in patients treated with TNF-
antagonists. In a previous study by a regional Swedish cohort, Geborek et al. [2] suggested that the overall incidence of cancer is not increased in patients treated with anti-TNF agents, while there may be an increased risk of lymphomas in those patients compared with RA patients treated with conventional agents. However, in the national Swedish cohort, including the data of the previous regional cohort, Askling et al. [3] could not find any increased risk for lymphomas in RA patients treated with TNF antagonists than other patients with RA. Setoguchi et al. [4] compared the risk of haematological malignancies and solid tumours in elderly RA patients from US and Canada who received biologic agents as compared with those treated with methotrexate. The authors found no significant increase in the risk of cancers in biologic agent users. Chakravarty et al. [5] and Wolfe and Michaud [6] demonstrated an increased risk of non-melanoma and all skin cancers in patients with RA treated with anti-TNF agents, respectively. In contrast to RA, disease-associated cancer risk has been poorly explored in AS. Recently, no overall increased risk for solid cancers or lymphomas were found in AS [7, 8]. Our nationwide survey did not show an increased risk of cancer associated with TNF antagonist use when data with etanercept, infliximab and adalimumab were considered together. On the other hand, there was an increase of cancer risk with etanercept use when these agents were considered separately and this trend was also present among RA patients taken as a separate group. There was no evidence for increased neoplasm among the AS patients.
Our study had several limitations: first, we did not re-confirm the cancer diagnoses neither clinically nor by histology. Second we did not seek information about the background risk factors for cancer, such as smoking status, or family history. Third, the comparator group for the cancer incidence represented only a limited geographic area [9]. Lastly, the total number surveyed as well as the number of cancer cases found is rather small to make robust comparisons.
Our results, which need to be interpreted in the light of shortcomings of our survey we mention above, nevertheless suggest that the risk of malignancy with the use of TNF antagonists might differ in different disease states (i.e. RA, SpAs), and with the use of different anti-TNF agents. Larger prospective collaborative studies with prolonged follow-up and more meticulous methodology will be needed in order to obtain more precise estimates.
The Executive Committee of The Society for Research and Education in Rheumatology would like to thank Dr Salih Pay and Dr Mehmet Akif Öztürk who managed this project, all other members who contributed to the present study, to Dr Mutlu Hayran for statistical assessment and to Dr Hasan Yaz
c for helpful comments in the preparation of the article.
APPENDIX 1. Complete list of members of The Society for Research and Education in Rheumatology who contributed to the present study (in alphabetical order).
Salih Pay (Gülhane Military Medical School)
M. Akif Öztürk (Gazi University School of Medicine)
Gerçek Can (Dokuz Eylul University School of Medicine)
Ay
e Cefle (Kocaeli University School of Medicine)
Veli Çobankara (Pamukkale University School of Medicine)
Burak Erer (Istanbul University, Istanbul Faculty of Medicine)
Feride Gö
ü (Gazi University, School of Medicine)
Gülen Hatemi (Istanbul University Cerrahpaa School of Medicine)
Nevsun 
nanç (Marmara University School of Medicine)
Yaar Karaaslan (Ankara Numune Education and Research Hospital)
Ömer Karada (Hacettepe University School of Medicine)
Yüksel Karakoç (Bursa Goverment Hospital)
Esen Kasapolu Günal (Maltepe University School of Medicine)
Timuçin Kaifolu (Osmangazi University School of Medicine)
Gökhan Keser (Ege University School of Medicine)
Serdar Koca (Frat University School of Medicine)
Selda Öktem (Memorial Hospital)
Hüseyin TE Özer (Cukurova University School of Medicine)
Mehmet Sayarlolu (Sütçü mam University School of Medicine)
Mehmet Soy (Trakya University School of Medicine)
Takn 
entürk (Adnan Menderes University School of Medicine)
Musa Temel (Haseki Education and Research Hospital)
Ender Terziolu (Akdeniz University School of Medicine)
Olcay Tiryaki (Ankara University School of Medicine)
Tufan Türk (Denizli Goverment Hospital)
Eftal Yücel (Baskent University School of Medicine)
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Acknowledgements |
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 Top Acknowledgements References |
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The Executive Committee of The Society for Research and Education in Rheumatology thanks to Dr Salih Pay and Dr Mehmet Akif Özturk who managed this project, all other members who contributed to the present study, to Dr Mutlu Hayran for statistical assessment and Dr Hasan Yazici for helpful comments in the preparation of the manuscript.
Disclosure statement: The author has declared no conflicts of interest.
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References |
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TopAcknowledgementsReferences |
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- Geborek P, Bladstrom A, Turesson C, 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 (2005) 64:699–703.
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