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

Tuesday, November 8, 2011: 5:00 PM
W375a (McCormick Place West)
Louise K. Mercer1, James B. Galloway1, Audrey SL Low1, Kath D. Watson1, Mark Lunt1, William G. Dixon1, British Society for Rheumatology Biologics Register (BSRBR) control centre consortium1, Deborah PM Symmons1, Kimme L. Hyrich1 and On behalf of the BSRBR2, 1Arthritis Research UK Epidemiology Unit, The University of Manchester, Manchester, United Kingdom, 2British Society for Rheumatology, London, United Kingdom
Presentation Number: 2525

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-naïve 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)




Keywords: anti-TNF, malignancy and rheumatoid arthritis

Disclosure: 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.