A Swedish population-based study shows that treatment with tumour necrosis factor (TNF) inhibitors significantly increases the risk of developing squamous cell carcinoma (SCC), but not basal cell carcinoma (BCC), in patients with rheumatoid arthritis.
The research also provides additional evidence to support the known association between rheumatoid arthritis and the elevated risk of developing non-melanoma skin cancer.
“Therefore, all patients with rheumatoid arthritis—regardless of treatment—might benefit from increased surveillance for skin cancer and should be advised to protect themselves from the sun”, says Shervin Assassi (University of Texas Health Science Center at Houston, USA) in an editorial published alongside the study in The BMJ.
Using data from the Swedish Biologics Register (ARTIS) and the Swedish National Cancer Register, the study authors identified 46,409 patients with rheumatoid arthritis who were naïve to TNF inhibitors and 12,558 who initiated anti-TNF therapy between 1998 and 2012. TNF-naive patients were matched by gender, year of birth and country of residence to 10 controls from the general population.
A total of 191 first in situ or invasive SCC were detected among TNF-treated patients, compared with 847 among those naïve to anti-TNF treatment, which equated to a significant hazard ratio (HR) of 1.30 after adjusting for demographical factors and comorbidity. And the risks were similar when in situ and invasive cases were analysed separately.
Assuming a causal relationship between TNFs and SCC, researcher Pauline Raaschou (Karolinska Institutet, Stockholm, Sweden) and colleagues estimate that their findings translate into an annual number needed to harm of around 1600, but they caution that the number “should be regarded as indicative of the order of magnitude rather than an exact figure”.
TNF treatment led to a moderate increase in the risk of developing BCC, with 236 first incidences among 8827 TNF-treated patients compared with 1587 cases among 43,675 untreated participants, but the increase was not significant after adjusting for demographics and comorbidities.
Assassi writes that “[i]n line with data from organ transplant literature, treatment with TNF inhibitors had a greater effect on the risk of SCC than of BCC, although the overall effect, even in the SCC group, was modest”, adding that “most of the overall risk originates from other factors including the disease itself”.
And indeed Raaschou et al found that relative to the general population, the risk of both SCC and BCC was significantly increased among TNF-naïve rheumatoid arthritis patients, with HRs of 1.88 and 1.22, respectively. These results are in line with previous studies that have shown a 20–80% increase in the risk of non-melanoma skin cancer for rheumatoid arthritis patients versus the general population, they say.
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