Cancer risk with tumor necrosis factor alpha (TNF) inhibitors: Meta-analysis of randomized controlled trials of adalimumab, etanercept, and infliximab using patient level data

Pharmacoepidemiology and Drug Safety

Volumn 20, Issue 2, 2011, Pages 119-130

  Askling, Johan ^a   Fahrbach, Kyle ^b   Nordstrom, Beth ^b   Ross, Susan ^b   Schmid, Christopher H ^c   Symmons, Deborah ^d  

^a KAROLINSKA INSTITUTE   (Sweden)

^b UNITED BIOSOURCE CORPORATION   (United States)

^c TUFTS MEDICAL CENTER   (United States)

^d UNIVERSITY OF MANCHESTER   (United Kingdom)

Author keywords

Cancer; Inflammatory bowel disease; Meta analysis; Rheumatoid arthritis; TNF; Trial

Indexed keywords

ADALIMUMAB; ETANERCEPT; IMMUNOSUPPRESSIVE AGENT; INFLIXIMAB; METHOTREXATE; PLACEBO; STEROID;

ARTICLE; CANCER RISK; DRUG INDUCED CANCER; FEMALE; FOLLOW UP; HUMAN; LYMPHOMA; MAJOR CLINICAL STUDY; MALE; META ANALYSIS; PATIENT CODING; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL (TOPIC); RHEUMATOID ARTHRITIS; RISK ASSESSMENT; SKIN CANCER;

ANTI-INFLAMMATORY AGENTS; ANTIBODIES, MONOCLONAL; BAYES THEOREM; EVIDENCE-BASED MEDICINE; HUMANS; IMMUNOGLOBULIN G; NEOPLASMS; RANDOMIZED CONTROLLED TRIALS AS TOPIC; RECEPTORS, TUMOR NECROSIS FACTOR; RISK ASSESSMENT; RISK FACTORS; TIME FACTORS; TREATMENT OUTCOME; TUMOR NECROSIS FACTOR-ALPHA;

EID: 78751685797     PISSN: 10538569     EISSN: 10991557     Source Type: Journal    
DOI: 10.1002/pds.2046     Document Type: Article

References (19)

1. Balkwill F. TNF-alpha in promotion and progression of cancer. Cancer Metastasis Rev 2006; 25(3): 409-416.
2. van Horssen R, Ten Hagen TL, Eggermont AM. TNF-alpha in cancer treatment: molecular insights, antitumor effects, and clinical utility. Oncologist 2006; 11(4): 397-408.
3. Bongartz T, Sutton AJ, Sweeting MJ, Buchan I, Matteson EL, Montori V. 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 2006; 295(19): 2275-2285.
4. Bongartz T, Warren FC, Mines D, Matteson EL, Abrams KR, Sutton AJ. Etanercept therapy in rheumatoid arthritis and the risk of malignancies. A systematic review and individual patient data meta-analysis of Randomized Controlled Trials. Ann Rheum Dis 2009; 68(7): 1177-1183.
5. Leombruno JP, Einarson TR, Keystone EC. The safety of anti-Tumor Necrosis Factor treatments in rheumatoid arthritis: meta and exposure adjusted pooled analyses of serious adverse events. Ann Rheum Dis 2009; 68(7): 1136-1145.
6. Askling J, Baecklund E, Granath F, et al. Anti-tumour necrosis factor therapy in rheumatoid arthritis and risk of malignant lymphomas: relative risks and time trends in the Swedish Biologics Register. Ann Rheum Dis 2009; 68(5): 648-653.
7. Askling J, Fored CM, Brandt L, et al. Risks of solid cancers in patients with rheumatoid arthritis and after treatment with tumour necrosis factor antagonists. Ann Rheum Dis 2005; 64: 1421-1426.
8. Setoguchi S, Solomon DH, Weinblatt ME, et al. Tumor necrosis factor alpha antagonist use and cancer in patients with rheumatoid arthritis. Arthritis Rheum 2006; 54(9): 2757-2764.
9. Wolfe F, Michaud K. Biologic treatment of rheumatoid arthritis and the risk of malignancy: analyses from a large US observational study. Arthritis Rheum 2007; 56(9): 2886-2895.
10. Askling J, van Vollenhoven RF, Granath F, et al. Cancer risk in patients with rheumatoid arthritis treated with anti-tumor necrosis factor alpha therapies: does the risk change with the time since start of treatment? Arthritis Rheum 2009; 60(11): 3180-3189.
11. Available from:
12. Wegener's Granulomatosis Etanercept Trial (WGET) Research Group. Etanercept plus standard therapy for Wegener's granulomatosis. N Engl J Med 2005; 352(4): 351-361.
13. Berry S, Berry D, Natarajan K, et al. Bayesian survival analysis with nonproportional hazards: metaanalysis of combination pravastatin-aspirin. JASA 2004; 99: 36-44.
14. Peyrin-Biroulet L, Deltenre P, de Suray N, et al. Efficacy and safety of tumor necrosis factor antagonists in Crohn's disease: meta-analysis of placebo-controlled trials. Clin Gastroenterol Hepatol 2008; 6(6): 644-653.
15. Geborek P, Bladström 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(5): 699-703.
16. Chakravarty EF, Michaud K, Wolfe F. Skin cancer, rheumatoid arthritis, and tumor necrosis factor inhibitors. J Rheumatol 2005; 32(11): 2130-2135.
17. Age-adjusted SEER incidence and U.S. death rates and 5-year relative survival rates by primary cancer site, sex and time period. Available from:
18. Askling J, Fored CM, Baecklund E, et al. Haematopoietic malignancies in rheumatoid arthritis: lymphoma risk and characteristics after exposure to tumour necrosis factor antagonists. Ann Rheum Dis 2005; 64(10): 1414-1420.
19. Mellemkjaer L, Linet MS, Gridley G, et al. Rheumatoid arthritis and cancer risk. Eur J Cancer 1996; 32A(10): 1753-1757.