Malignancy risk in Australian rheumatoid arthritis patients treated with anti-tumour necrosis factor therapy: analysis of the Australian Rheumatology Association Database (ARAD) prospective cohort study.
BACKGROUND
Malignancy risk with tumour necrosis factor inhibitor (TNFi) therapy remains unclear. Our primary aim was to assess malignancy risk with TNFi therapy in a cohort of Australian patients with rheumatoid arthritis (RA). We also assessed risk in a biologic-naïve group.


METHODS
Demographic data of all RA patients enrolled in the Australian Rheumatology Association Database before 25 October 2010 were matched to national cancer records in July 2010 (linkage complete to 2007). Verified self-reported malignancies occurring between 1 January 2008 and 25 October 2010 were also included in the analysis. Standardised incidence ratios (SIRs) were used to compare malignancy incidence in biologic-naïve and TNFi-exposed ARAD participants to the general population using site-, age- and sex-specific rates by calendar year. Rate ratios (RRs) were used to compare malignancy incidence in TNFi-exposed participants to biologic-naïve RA patients, and a composite RA cohort that included pre-TNFi person years, both adjusted for age, gender, smoking, methotrexate use and prior malignancy.


RESULTS
Forty-four malignancies were reported after 5752 person-years in the TNFi-exposed group (N = 2145) and 32 malignancies were reported after 1682 person-years in the biologic-naïve group (N = 803). No overall increased risk of malignancy in TNFi-treated RA patients was found when compared with the general population or with biologic-naïve RA patients. Compared to the biologic naïve group, without the inclusion of pre-TNFi years in the comparator group, the relative risk of female breast cancer was reduced in TNFi-treated patients (RR 0.17 (95 % CI 0.03 to 0.95)). It was no longer significant when adding pre-TNFi years in the comparator group. The risk of melanoma was increased for both biologic naïve and TNFi-treated patients when compared with the general population (SIR 2.72 (95 % CI 1.13 to 6.53) and SIR 2.03 (95 % CI 1.09 to 3.78) respectively). The relative risk of melanoma was not increased in the TNFi-exposed group compared with biologic naïve patients (RR 0.54, 95 % CI 0.12, 2.40). Inclusion of pre-TNFi person years in the comparator group did not change these results.


CONCLUSIONS
Malignancy incidence was low in this RA cohort and biologic exposure did not increase the risk of malignancy. Melanoma risk was increased in both TNFi-treated and biologic-naïve RA patients compared with the general population suggesting that RA status, and possibly methotrexate exposure, may be responsible.
Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia. rachelle.buchbinder@monash.edu.|Monash Department of Clinical Epidemiology, Cabrini Institute, Melbourne, Australia. rachelle.buchbinder@monash.edu.
Rachelle
R
Buchbinder
Department of Medicine (Royal Melbourne Hospital), The University of Melbourne, Melbourne, Australia. svd@unimelb.edu.au.
Sharon
S
Van Doornum
Department of Epidemiology and Preventive Medicine, School of Public Health and Preventive Medicine, Monash University, Melbourne, Australia. margaret.staples@monash.edu.|Monash Department of Clinical Epidemiology, Cabrini Institute, Melbourne, Australia. margaret.staples@monash.edu.
Margaret
M
Staples
St George Hospital, University of New South Wales, Sydney, Australia. Marissa.Lassere@sesiahs.health.nsw.gov.au.
Marissa
M
Lassere
Florance and Cope Professorial Department of Rheumatology, Royal North Shore Hospital, Institute of Bone and Joint Research, University of Sydney , Sydney, Australia. lyn.march@sydney.edu.au.
Lyn
L
March
D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy*; D001315:Australia / Q000453:epidemiology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000139:chemically induced* / Q000453:epidemiology; D011446:Prospective Studies; D018570:Risk Assessment; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors*
D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha