“Risk of solid cancer in patients exposed to anti-tumor necrosis factor therapy: results from the British Society for Rheumatology Biologics Register for Rheumatoid Arthritis”

Mercer, L. et al. Ann Rheum Dis , published on line first 31 March 2014

Authors compared the risk of solid cancer in patients with rheumatoid arthritis treated with TNF inhibitors to that in patients treated with non-biologic (synthetic) disease modifying anti-rheumatic drugs (sDMARDs).

British Society for Rheumatology Biologic Register was established in 2001 to monitor for long-term safety of TNF inhibitors. Patients from that register were followed via record linkage with the national cancer registries until first solid cancer, death, for 5 years or until 2011. Solid cancer rates in 11767 patients without prior cancer treated with TNF inhibitor were compared to those in 3249 patients without prior cancer treated with sDMARDs (ex., methotrexate, sulfasalazine, leflunomide).

81 cancers per 10000 patient-years were reported for the TNF inhibitor group and 117 cancers per 10000 patient-years for sDMARD group. There were no differences in risk of solid cancer for TNF inhibitors compared to sDMARD treated patients.

The authors concluded that addition of TNF inhibitor to sDMARD does not increase the risk of cancer in rheumatoid arthritis patients selected for TNF inhibitors in the UK.




Systematic review with meta-analysis: malignancies with anti-tumor necrosis  factor-a therapy in inflammatory bowel disease.
Williams CJ et al. Aliment Pharmacol There, 2014 Mar; 39(5):447-58.
Authors reviewed 22 randomized-controlled studies. Those included studies on the infliximab, adalimumab, certolizumab, and golimumab used in treatment of the inflammatory bowel disease (IBD). There were 16 cases (0.39%) of malignancies in 4135 IBD patients using anti-TFF-a inhibitors compared with 13 (0.45%) in 2919 patients being as controls.  There were no cases of lymphoma in active treatment group compared with three (0.1%) in the control group. The authors concluded that the anti-TNF-a treatment was not associated with an increased risk of malignancy in patients with IBD. The duration of the studies included to the analysis was up to a year, meaning that an increased risk in the long term can not be excluded.
TNF inhibitor (TNFi) biologics and malignancy risk
in Rheumatoid arthritis (RA)
1. Relative risk of lymphoma in RA patients treated with TNFi biologics:
  • Compared to TNFi-naive RA patients            1.35 (95% CI 0.82-2.11)
  • Compared to general population                  2.72 (95% CI 1.82-4.08)

Reference: Askling J et al. Ann Rheum Dis. 2009; 68:648-653.

Comment: risk appears mostly driven by the disease (RA) rather than the TNFi biologic, but such risk can not be excluded.

2. Risk of skin cancer in RA patients treated with TNFi biologics compared to other RA patients (Odds ratio):
  • Non melanoma skin cancer        1.5 (95% CI 1.2-1.8)
  • Melanoma                                2.3 (95% CI 0.9-5.4)

Reference: Wolfe F et al. Athritis Rheum. 2007. Sep; 56 (9):2886-95

Comment: TNFi biologics appear increase the risk of skin cancer.

3. Risk of solid cancers in RA patients (SIR):
  • All RA patients compared to general population      1.05 (95% CI 1.01-1.08)
  • TNFi biologics compared to other RA patients          0.9 (95% CI 0.7-1.2)

Reference: Askling J et al. Ann Rheum Dis. 2005 Oct; 64(10);1421-1426

Comment: RA patients appear to have a slightly increased overall risk of solid tumours. This is possibly on the basis of smoking-related cancers. Use of TNFi biologics do not appear to increase the risk of solid cancers (excluding skin cancer).