Biologic therapies and non-melanoma skin cancer rates in three chronic immune-mediated diseases

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Today, a number of studies have found a causal relationship between inflammation, innate immunity and cancer. Nevertheless many of the molecular and cellular mechanisms mediating this relationship remain unresolved and the magnitude of the association is still unclear. Several factors can stimulate carcinogenesis in patients with autoimmune disease, particularly rheumatoid arthritis (RA), Crohn's disease (CD) and psoriasis including chronic inflammation and immune dysregulation, the use of immunosuppressive drugs, and exposure to environmental factors. The role of inflammatory cells and the chemokines and cytokines that they produce is controversial: they have a beneficial effect on the host, enhancing the immunological responses against infectious agents and tumour cells; but they are also powerful tumour promoters, producing an attractive environment for tumour growth, facilitating genomic instability and promoting angiogenesis. It is recognized that immunosuppression may lead to reduced immune surveillance and tumour formation. Because of the immunosuppressive properties of different traditional systemic therapies and biologic therapies, it is plausible that these drugs may increase the occurrence of malignancies or reactivation of latent ones, including non-melanoma skin cancers (NMSC). Biologic medications have revolutionized treatment of several significant inflammatory autoimmune diseases. Nevertheless, issues concerning long-term safety remain to be clarified. The purpose of this thesis was to carry out a review of literature on the impact on cancer risk, mainly NMSC, of different drug classes, especially biologicals, used in the treatment of immune-mediated inflammatory diseases (IMIDs) as well as understand the role of inflammation in cancer and cancer risk in IMIDs. Overall cancer incidence and mortality risk in RA, CD and psoriasis is slightly elevated in comparison to the general population, with risk profiles differing for different tumor types. Increased risk for NMSC is associated with anti-TNF treatment of RA, especially when combined with methotrexate, with PUVA, cyclosporine and anti-TNF treatment in psoriasis, which have an inherent risk for NMSC, and with thiopurine treatment in CD. Only limited data are available on the impact of anti-TNF treatment on cancer risk in CD. As opposed to cancer incidence, sparse data are available on the safety of using biologic or immunosuppressant therapy in IMIDs patients with premalignancy states. Appropriate patient counseling and selection, as well as clinical follow-up, are necessary to maximize safety with biologic therapies. Further long-term controlled clinical trials and registries are required to more precisely quantify the risks associated with these therapies.