The relationship between tumor necrosis factor-α inhibitors (TNFi) and cancer risk is complex, given their pivotal role in managing chronic inflammatory conditions. Persistent concerns about TNFi therapy potentially increasing cancer risk necessitate a thorough understanding of its long-term effects on cancer development in patients with psoriasis to guide therapeutic decision-making. This systematic review and meta-analysis aimed to evaluate the association between long-term TNFi therapy and cancer risk in patients with psoriasis. Data were collected from PubMed, Embase, and the Cochrane Library, from their inception to January 1, 2024. The studies included adults with psoriasis or psoriatic arthritis receiving TNFi, presenting standardized incidence ratio (SIR) data for cancer. Data extraction followed PRISMA guidelines, with independent extraction by two authors, and pooled data synthesis was conducted using a random-effects model. The primary outcomes were SIRs for all cancers excluding non-melanoma skin carcinoma (NMSC) and for NMSC itself. The secondary outcome was the SIR of specific cancer types. The meta-analysis included eight studies with a total of 32,765 psoriasis patients. The pooled results showed no increased risk of cancers, including all cancers excluding NMSC, melanoma, lymphoma, prostate cancer, and breast cancer, among individuals receiving long-term TNFi therapy for psoriasis compared to the general population. However, subgroup analysis found an elevated risk of NMSC in patients with psoriatic arthritis and a significant increase in the risk of squamous cell carcinoma (SCC) among psoriasis patients treated with TNFi compared to the general population (SIR, 1.84; 95% CI, 1.16 - 2.92 and SIR, 2.84; 95% CI, 1.64 - 4.91, respectively). Our systematic review and meta-analysis indicate that most cancers examined did not demonstrate an increased risk following long-term TNFi therapy in psoriasis patients. However, for patients with psoriatic arthritis or those at high risk of SCC, these findings underscore the importance of personalized treatment strategies that weigh individual risks and benefits.
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