Biologic Therapy and the Risk of Malignancy in Psoriasis

Abstract

Biologic agents are currently regarded as a highly efficacious systemic treatment for moderate to severe psoriasis. However, their use in patients with a history of malignancy or an increased risk of cancer is not recommended. The current recommendations are based on several case reports and observational studies, as well as data from randomized, controlled trials, associating these medications with tumorigenic properties. Furthermore, some reports describe malignancies arising de novo in patients using biologic agents. Psoriasis patients are at an increased risk of lymphoproliferative diseases and nonmelanoma skin cancers because of the inflammatory nature of the disease. A blockade of tumor necrosis factor-alpha (TNF-α) reduces inflammation but also may enhance tumor proliferation. Trials have not shown a significant increase in the risk of malignancy, with the exceptions of lymphoma and nonmelanoma skin cancers, with the use of TNF blockers. However, any risk may be unacceptable in a patient with a history or elevated risk of cancer. Ustekinumab acts on a different inflammatory pathway and may have a different profile regarding the risk of malignancy. A comprehensive review of the literature shows some consensus that relative contraindications are active malignancies and malignancies within the past 5 years. There is debate about nonmelanoma skin cancers and melanoma, but it seems prudent to use biologics more cautiously in a patient with a history of aggressive skin cancer, a high risk of recurrent skin cancer, or a history of extreme ultraviolet exposure. Additionally, certain combinations of immunosuppressive therapies, such as purine analogs, with biologics may lead to unacceptable risks of malignancy. Some subgroups, such as patients with chronic obstructive pulmonary disease, are already predisposed to lung cancer because of a significant smoking history; these patients require closer monitoring during biologic therapy. As the biologics are in use longer for psoriasis, more data on the long-term safety of these therapeutics will be available.