Rheumatoid arthritis and lymphoma: the role of disease-modifying anti-rheumatic drugs
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A well-functioning immune system is of paramount importance in preventing lymphomagenesis. Both immunostimulation, which causes excessive cell turnover and increased potential for mutations, and immunosuppression, causing a decreased ability to monitor and halt aberrant cell proliferation, have been implicated in cancer development. Autoimmune diseases are characterized by excessive activation of lymphocytes due to a dysregulated response to self-antigens. The treatments for autoimmune disease therefore share a common goal of immunosuppression. While treatments have become better-targeted to specific inflammatory pathways over the last 30 years as opposed to general immunosuppression, there remains a high risk of hematologic malignancy for patients with autoimmune disease relative to the general population. There are numerous types of autoimmune disease, as well as much heterogeneity within each diagnosis from patient to patient. The focus of this thesis is Rheumatoid Arthritis (RA), a strikingly common disease affecting 0.5-1.0% of the world population and characterized by debilitating, painful, joint-deforming symptoms and difficulty in achieving remission.  Therapeutic intervention often necessitates a trial and error approach and various combinations of drugs, in the same way cocktails of chemotherapeutic drugs are tailored to treat cancers due to their heterogeneity. Drugs for the treatment of autoimmune diseases are collectively known as Disease-Modifying Anti-Rheumatic Drugs (DMARDs) and were only first widely used for the treatment of RA in the 1980s. This short history of widespread use, along with the great variability in manifestation of disease and treatment course, has historically limited the ability of observational studies to determine the safety of DMARDs in terms of malignancy risk. Only in the past few years has enough information been available, drawn mostly from national healthcare databases in several countries, to enable strong conclusions about the effects of DMARDs on malignancy risk. This thesis aims to provide a comprehensive review of the most recent and well-designed studies regarding currently available DMARDs for RA and their effects on the risk of lymphoma.