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CHICAGO - Anti tumor necrosis factor therapy does not increase the overall risk of solid cancer in people with rheumatoid arthritis, according to research presented this week at the American College of Rheumatology Annual Scientific Meeting in Chicago.

Rheumatoid arthritis is a chronic disease that causes pain, stiffness, swelling, and limitation in the motion and function of multiple joints. Though joints are the principal body parts affected by RA, inflammation can develop in other organs as well. An estimated 1.3 million Americans have RA, and the disease typically affects women twice as often as men.

There has been a concern that the use of anti-TNF therapy to treat and manage rheumatoid arthritis may be associated with an increased risk of developing cancerous tumors. However, several patient studies have been unable to identify a connection between anti-TNF therapy usage and cancer. Researchers from the University of Manchester in the United Kingdom assumed that the short length of clinical trials may fail to spot new cancer cases and therefore they are following patients receiving these drugs in routine care for a minimum of five years to determine if anti-TNF therapy elevates cancer risk in people with rheumatoid arthritis.

“It is important to look at effects of long-term treatment with anti-TNF as patients with RA often take this therapy for several years. Some cancers take many years to develop and clinical trials lasting only six to 12 months may be too short to look for a link between anti-TNF and cancer,” says Kimme L. Hyrich, MD, PhD, FRCPC; senior lecturer and consultant in rheumatology at the University of Manchester in the United Kingdom and lead investigator of the study.

Researchers evaluated data from the British Society for Rheumatology Biologics Register—a registry that tracks the progress of patients with severe rheumatoid arthritis and other rheumatic diseases who are taking anti-TNF therapy. Patients with RA were followed for up to five years after starting treatment with the anti-TNF therapies etanercept (Enbrel®), infliximab (Remicade®) or adalimumab (Humira®). A second group of patients who had never received anti-TNF therapy, but who were taking disease-modifying antirheumatic drugs (commonly called DMARDs) were also included in the study.

New cancer cases were identified by reviewing annual physician questionnaires and lifelong health information from the United Kingdom cancer registry.

Statistical tests were used to compare the number of cancers in patients who had taken anti-TNF treatment to the number in patients who had never taken anti-TNF treatment. Seven factors were used to estimate cancer risk including age, gender, years diagnosed with RA, nonsteroidal anti-inflammatory drug usage, presence of other diseases, smoking and the year each participant was registered in the study. Participants with a history of cancer prior to the study were excluded.

Among the 15,262 participants, 386 cancer cases were recorded: 91 among 3,543 participants taking DMARDs and 295 among 11,719 participants taking anti-TNF. Researchers concluded there was not a significant difference in the overall risk of cancer between the two groups. The researchers also noted no significant differences in developing the three most common cancers in patients with RA - namely colorectal, lung and breast cancer. Moreover, cancer risk did not increase during the length of the study.

“We found that the risk of cancer was no different in patients receiving anti-TNF compared to those who had never received this therapy. We also could not identify a difference in risk between the three anti-TNF drugs studied. This should reassure patients and their physicians as this was a large study, looking at real-life practice in the UK. The study continues to look at the effect of receiving anti-TNF for longer than five years,” says Dr. Hyrich.

TNF-antagonists (anti-TNF therapy; among drugs called biologics) are a class of drugs that have been used since 1998. Overall, they have been given to more than 600,000 people worldwide. These drugs are given to lessen inflammation by interfering with biologic substances that cause or worsen inflammation.

Patients should talk to their rheumatologists to determine their best course of treatment.

The American College of Rheumatology is an international professional medical society that represents more than 8,000 rheumatologists and rheumatology health professionals around the world. Its mission is to advance rheumatology. The ACR/ARHP Annual Scientific Meeting is the premier meeting in rheumatology. For more information about the meeting, visit Follow the meeting on Twitter by using the official hashtag: #ACR2011.

Editor’s Notes: Kimme L. Hyrich, MD, PhD, FRCP, will present this research during the ACR Annual Scientific Meeting at McCormick Place Convention Center  at 5:00 pm on Tuesday, November 8 in Room W 375 A. Dr. Hyrich will be available for media questions and briefing at 1:30 pm on Monday, November 7 in the on-site press conference room, W 175C.

Learn more about living well with rheumatic disease as well as rheumatologists and the role they play in health care. Also, discover the ACR’s Simple Tasks campaign, which highlights the severity of rheumatic diseases and the importance of early and appropriate referral to a rheumatologist.

Presentation Number: 2525

The Risk of Solid Cancer in Patients Receiving Anti-Tumour Necrosis Factor Therapy for Rheumatoid Arthritis for up to 5 Years: Results From the British Society for Rheumatology Biologics Register

Kimme L. Hyrich (Arthritis Research UK Epidemiology Unit, The University of Manchester, Manchester, United Kingdom)
Louise K. Mercer (Arthritis Research UK Epidemiology Unit, The University of Manchester, Manchester, United Kingdom)
James B. Galloway (Arthritis Research UK Epidemiology Unit, The University of Manchester, Manchester, United Kingdom)  
Audrey SL Low (Arthritis Research UK Epidemiology Unit, The University of Manchester, Manchester, United Kingdom)
Kath D. Watson ((Arthritis Research UK Epidemiology Unit, The University of Manchester, Manchester, United Kingdom)  
Mark Lunt (Arthritis Research UK Epidemiology Unit, The University of Manchester, Manchester, United Kingdom)
William G. Dixon (Arthritis Research UK Epidemiology Unit, The University of Manchester, Manchester, United Kingdom)

Background/Purpose: The use of TNF inhibitors in the management of rheumatoid arthritis (RA) has been coupled with concerns about tumorigenesis. Meta-analysis of patient-level data from randomised controlled trials (RCT) has not found an increased risk of solid cancer. The short duration and strict exclusion criteria of RCTs means latent events such as cancer may be missed. The aim of this study was to determine whether anti-TNF influences the risk of cancer when used in routine UK clinical practice.

Method: The analysis was conducted in the British Society for Rheumatology Biologics Register (BSRBR), a national cohort study. Patients with RA starting treatment with the TNF inhibitors etanercept (ETA), infliximab (INF) or adalimumab (ADA) and a biologic-naí¯ve comparison cohort exposed to non-biologic therapy (DMARD) were recruited between 2001-2009. The first six months of follow up for each subject was excluded from the analysis. Subjects were followed for 5 years, until 31/12/2009 or death, whichever came first. Subjects with a history of solid cancer prior to registration identified by record linkage with the UK cancer registry (NHS-IC) were excluded. Incident cancers were identified in 3 ways; lifelong flagging with NHS-IC; 6 monthly patient and physician questionnaires for 3 years and annual physician questionnaires thereafter. Only the first solid cancer per subject (excluding non-melanoma skin cancer), confirmed by histology or NHS-IC, was analysed. Cancers occurring after stopping anti-TNF were attributed to the most recent anti-TNF. The rates of solid cancer in the anti-TNF and DMARD cohorts were compared using multivariate Cox proportional hazards models adjusted using inverse probability of treatment weighting (IPTW) for age, gender, comorbidity, disease duration, use of NSAIDs, smoking and registration year. Site specific analyses were performed for sites with ≥10 cancers in each cohort: colorectal, lung/bronchus and female breast. 

Result: 386 solid cancers were confirmed:  91 in 3543 DMARD patients and 295 in 11719 anti-TNF patients (84 v 63 per 10000 patient-years (pyrs)) (Table). After adjusting for IPTW there was no difference in risk of solid cancer between the 2 cohorts (hazard ratio (HR) for anti-TNF 0.88 (0.65, 1.17)). The IPTW adjusted HR for ETA was 0.94 (0.68, 1.29), INF 0.87 (0.61, 1.25) and ADA 0.81 (0.57, 1.14). There was no significant difference in risk of colorectal, lung/bronchus or female breast cancer for anti-TNF compared to DMARD. The risk did not vary with duration of follow up. 

Conclusion: In patients without prior solid cancer no increase in solid cancer risk was seen in this UK national cohort of RA patients treated with TNF inhibitors when followed for up to 5 years. Further follow up is warranted to further assess site specific risk and allow for longer latency.








Follow-up (pyrs)






Age: Mean (SD)

60 (12)

56 (12)

56 (12)

56 (12)

56 (12)

Gender: N(%) female

2552 (72)

8915 (76)

3135 (77)

2586 (75)

3194 (76)

Solid cancer: N






Solid: Rate per 10000 pyrs

84 (68, 103)

63 (57, 71)

68 (57, 81)

61 (48, 77)

60 (48, 73)

Solid: Unadjusted HR


0.73 (0.58, 0.93)

0.77 (0.59, 1.01)

0.72 (0.53, 0.98)

0.69 (0.51, 0.92)

Solid: Age and gender adjusted HR


0.94 (0.74, 1.20)

1.03 (0.78, 1.35)

0.91 (0.66, 1.24)

0.87 (0.65, 1.17)

Solid: IPTW adjusted HR


0.88 (0.65, 1.17)

0.94 (0.68, 1.29)

0.87 (0.61, 1.25)

0.81 (0.57, 1.14)

Colorectal: N






Colorectal: Rate per 10000 pyrs

9 (4, 17)

5 (3, 7)




Colorectal: IPTW adjusted HR


1.21 (0.54, 2.70)




Lung: N






Lung: Rate per 10000 pyrs

20 (13, 31)

16 (12, 20)




Lung: IPTW adjusted HR


0.89 (0.46, 1.74)




Female breast: N






Female breast: Rate per 10000 pyrs

7 (3, 11)

6 (4, 7)




Female breast: IPTW adjusted HR


0.99 (0.51, 1.92)




L. K. Mercer, None.
J. B. Galloway, None.
A. S. Low, None.
K. D. Watson, None.
M. Lunt, None.
W. G. Dixon, None.
B. S. F. R. B. R. (BSRBR) control centre consortium, None.
D. P. Symmons, None.
K. L. Hyrich, None.
O. B. O. T. BSRBR, None.

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