Abstract
BackgroundMalignancy 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.MethodsDemographic 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.ResultsForty-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.ConclusionsMalignancy 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.
Highlights
Malignancy risk with tumour necrosis factor inhibitor (TNFi) therapy remains unclear
A systematic review of adalimumab and infliximab randomised controlled trials in rheumatoid arthritis (RA) patients reported a significantly higher malignancy risk compared with placebo [3]
Based upon findings from individual studies they concluded that TNFi exposure is not associated with an increased overall risk of malignancy, lymphoma or non-melanoma skin cancer (NMSC) but may be associated with a slight increased risk of melanoma based upon a single study [23]
Summary
Malignancy risk with tumour necrosis factor inhibitor (TNFi) therapy remains unclear. While several groups have demonstrated an increased risk of lymphoma with TNFi therapy [10,11,12], which may just reflect the known increased risk in RA [13, 14], observational studies have generally reported no increased risk of malignancy overall [10, 11, 15,16,17,18,19,20]. A 2011 systematic review of prospective observational studies supported these findings (pooled estimate of overall risk of malignancy 0.95, 95 % CI 0.85-1.05 compared with RA TNFi-naïve controls), the risk of non-melanoma skin cancer (NMSC) was increased (pooled estimate of risk 1.45, 95 % CI 1.15-1.76) [21]. Based upon findings from individual studies they concluded that TNFi exposure is not associated with an increased overall risk of malignancy, lymphoma or NMSC but may be associated with a slight increased risk of melanoma based upon a single study [23]
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