Background Anti-tumour necrosis factor (anti-TNF) therapy has been widely used for refractory rheumatoid arthritis (RA) and psoriatic arthritis (PsA) over the past 10 years. Safety data from randomised controlled trials (RCTs) and cohort studies have identified a potentially increased risk of malignancy, particularly skin cancers.

Objectives To investigate the risk of skin cancer following anti-TNF therapy in RA and PsA patients.

Methods We conducted a systematic literature review using the Cochrane Library, EMBASE, PubMed and Web of Science databases. Only human RCTs and cohort studies published in English were analysed. Data extracted for comparison included study population characteristics, prior exposures, confounding factors, interventions, number and type of malignancies (specifically melanomas, basal cell and squamous cell carcinomas). Risk of study bias was assessed based on the Cochrane Risk of Bias Assessment Tool.

Results Of the 282 results that were obtained from the literature search, 15 met the inclusion criteria. We analysed 5 RCTs and 10 cohort studies, covering a total of 358,734 patients. Three of 15 studies reported significant odds or hazard ratios for non-melanoma skin cancers (NMSCs) in RA patients treated with anti-TNFs. There was an increased risk of NMSCs (hazard ratio (HR): 1.42 [1.23-1.65]) with anti-TNF treatment in a population of 19,200 American veterans (90.7% male) as well as in a large observational study involving 13,001 patients (Odds ratio: 1.5 [1.2-1.81). The risk of NMSCs was increased in one study when anti-TNF was combined with methotrexate (HR: 1.97 [1.51-2.58] compared with anti-TNF without methotrexate HR: 1.24 [0.97-1.581). There was no increased risk of melanomas documented in RA patients treated with anti-TNFs. There was insufficient data to comment on PsA cohorts.

Conclusions RA patients treated with anti-TNF agents may be at an increased risk of developing NMSCs, particularly the male RA patient population and those taking concomitant methotrexate. This risk should be considered when commencing anti-TNF therapy. We did not find an increased risk of melanomas with anti-TNF therapy in RA patients. Further investigation is required to determine a relationship between skin cancers and anti-TNF therapy in PsA patients.

References

1. Amari, W., A. L. Zeringue, J. R. McDonald, L. Caplan, S. A. Eisen, and P. Ranganathan. 2011. Risk of non-melanoma skin cancer in a national cohort of veterans with rheumatoid arthritis. Rheumatology (Oxford) 50 (8):1431-9. doi: 10.1093/rheumatology/ker113.

2. Wolfe, F., and K. Michaud. 2007. Biologic treatment of rheumatoid arthritis and the risk of malignancy: analyses from a large US observational study. Arthritis Rheum 56 (9):2886-95. doi: 10.1002/art.22864.

3. Chakravarty, E. F., K. Michaud, and F. Wolfe. 2005. Skin cancer, rheumatoid arthritis, and tumor necrosis factor inhibitors. J Rheumatol 32 (11):2130-5.

Disclosure of Interest R. Chatterjea: None declared, M. Mc Laughlin: None declared, I. Kuhn: None declared, A. Östör Grant/research support from: Roche, Lilly, Chugai, MSD, Abbvie, Pfizer, Novartis, Napp & BMS., Consultant for: Roche, Lilly, Chugai, MSD, Abbvie, Pfizer, Novartis, Napp & BMS.