Risk of non-melanoma skin cancer for rheumatoid arthritis patients receiving TNF antagonist: a systematic review and meta-analysis

Objective Tumor necrosis factor inhibitors (anti-TNF) have become the standard treatment for rheumatoid arthritis (RA). However, evidence is inconsistent as to whether RA patients with anti-TNF are associated with an increased risk of non-melanoma skin cancer (NMSC) compared with those without anti-TNF. We performed a systematic review and meta-analysis to evaluate the risk of NMSC in patients with anti-TNF drugs compared with those without anti-TNF. Methods We did a systematic literature search with PubMed, EMBASE, and the Cochrane Library from inception to April 1, 2019. Prospective observational studies were eligible for inclusion if they included any of the approved anti-TNF drugs and reported the risk estimates and 95% confidence interval (95% CI) of NMSC associated with anti-TNF in RA patients. Pooled relative risks (RRs) and 95% CIs were calculated using a fixed-effects model. To assess the heterogeneity and risk of publication bias, we respectively conducted the subgroup and sensitivity analysis, funnel plot, Begg's and Egger's test. Results The present meta-analysis included six studies with 123,031 patients. Compared with RA patients without anti-TNF, patients with anti-TNF drugs were associated with an increased risk of NMSC (RR 1.28, 95% CI 1.19 to 1.38; I-2 = 45.6%, P = 0.056), especially squamous cell skin cancer (SCC) (RR 1.30, 95% CI 1.09 to 1.54; I-2 = 0%, P = 0.854), but not basal cell skin cancer (RR 1.13, 95% CI 0.97 to 1.31; I-2 = 0%, P = 0.555). Sensitivity and subgroup analysis confirmed the robustness of the primacy results. There was no evidence of publication bias with Begg's and Egger's test or by inspection of the funnel plot. Conclusions These results suggest that RA patients treated with anti-TNF are at an increased risk of NMSC, especially SCC. However, this association in RA urgently needs the more clinical studies and basic researches to further validate.