Incidence of Malignancy in Adult Patients With RA
Incidence of Malignancy in Adult Patients With RA
Introduction: The risk of malignancies in patients with rheumatoid arthritis (RA) has raised some concern, particularly with immunosuppressive approaches to disease management.
Methods: We conducted a systematic review of the literature and meta-analysis characterizing the associated risk of overall malignancy and four site-specific malignancies (lymphoma, lung, colorectal, and breast cancer) in patients with RA. A Medline search from 1990 to 2007 was conducted using specified search terms and predefined inclusion criteria for identification of relevant observational studies that provide estimates of relative risk of malignancy associated with RA. Study-specific estimates of the relative risk, as measured by standardized incidence ratios (SIRs) and estimated in comparison with the general population, were combined using a random effects model.
Results: A total of 21 publications were identified, of which 13 reported the SIR for overall malignancy, 14 for lymphoma, 10 for colorectal, 12 for lung, and 9 for breast cancer. Compared with the general population, the overall SIR estimates suggest that RA patients have approximately a two-fold increase in lymphoma risk (SIR 2.08, 95% confidence interval [CI] 1.80 to 2.39) and greater risk of Hodgkin than non-Hodgkin lymphoma. The risk of lung cancer was also increased with an SIR of 1.63 (95% CI 1.43 to 1.87). In contrast, a decrease in risk was observed for colorectal (SIR 0.77, 95% CI 0.65 to 0.90) and breast (SIR 0.84, 95% CI 0.79 to 0.90) cancer. The SIR for overall malignancy was 1.05 (95% CI 1.01 to 1.09).
Conclusion: Patients with RA appear to be at higher risk of lymphoma and lung cancer and potentially decreased risk for colorectal and breast cancer compared with the general population.
Rheumatoid arthritis (RA) is a chronic autoimmune disease that is also characterized by the presence of inflammation. Because of the immune pathways underlying its pathogenesis and what has generally been an immunosuppressive approach to disease management using traditional disease-modifying antirheumatic drugs (DMARDs), the risk of malignancies among RA patients has been of considerable interest. The characterization of this potential risk has become more relevant with the introduction of a new class of agents, biologic DMARDs. While these drugs act by directly modifying immunologic pathways involved in the pathogenesis of RA, it has been of concern that their use may be associated with an increased incidence of cancer. To better understand and interpret studies evaluating the risk associated with these agents, it is first necessary to determine the magnitude of any underlying risk of cancer that may already be present in patients with RA compared with the general population.
Data from several studies, reviewed by Chakravarty and Genovese, have suggested that there is no increase in the overall risk of cancer in patients with RA compared with the general population. However, accumulating evidence has suggested that the RA population may be characterized by changes in the relative risk of site-specific malignancies. Consequently, the objective of this study was to review the risk of four important site-specific malignancies (lymphoma, lung, colorectal, and breast cancer) in patients with RA in the recent published literature. In particular, this review focused on observational studies comparing the incidence of malignancy in patients with RA versus the general population since these may be expected to provide a realistic perspective on risk in the clinical setting.
Abstract and Introduction
Abstract
Introduction: The risk of malignancies in patients with rheumatoid arthritis (RA) has raised some concern, particularly with immunosuppressive approaches to disease management.
Methods: We conducted a systematic review of the literature and meta-analysis characterizing the associated risk of overall malignancy and four site-specific malignancies (lymphoma, lung, colorectal, and breast cancer) in patients with RA. A Medline search from 1990 to 2007 was conducted using specified search terms and predefined inclusion criteria for identification of relevant observational studies that provide estimates of relative risk of malignancy associated with RA. Study-specific estimates of the relative risk, as measured by standardized incidence ratios (SIRs) and estimated in comparison with the general population, were combined using a random effects model.
Results: A total of 21 publications were identified, of which 13 reported the SIR for overall malignancy, 14 for lymphoma, 10 for colorectal, 12 for lung, and 9 for breast cancer. Compared with the general population, the overall SIR estimates suggest that RA patients have approximately a two-fold increase in lymphoma risk (SIR 2.08, 95% confidence interval [CI] 1.80 to 2.39) and greater risk of Hodgkin than non-Hodgkin lymphoma. The risk of lung cancer was also increased with an SIR of 1.63 (95% CI 1.43 to 1.87). In contrast, a decrease in risk was observed for colorectal (SIR 0.77, 95% CI 0.65 to 0.90) and breast (SIR 0.84, 95% CI 0.79 to 0.90) cancer. The SIR for overall malignancy was 1.05 (95% CI 1.01 to 1.09).
Conclusion: Patients with RA appear to be at higher risk of lymphoma and lung cancer and potentially decreased risk for colorectal and breast cancer compared with the general population.
Introduction
Rheumatoid arthritis (RA) is a chronic autoimmune disease that is also characterized by the presence of inflammation. Because of the immune pathways underlying its pathogenesis and what has generally been an immunosuppressive approach to disease management using traditional disease-modifying antirheumatic drugs (DMARDs), the risk of malignancies among RA patients has been of considerable interest. The characterization of this potential risk has become more relevant with the introduction of a new class of agents, biologic DMARDs. While these drugs act by directly modifying immunologic pathways involved in the pathogenesis of RA, it has been of concern that their use may be associated with an increased incidence of cancer. To better understand and interpret studies evaluating the risk associated with these agents, it is first necessary to determine the magnitude of any underlying risk of cancer that may already be present in patients with RA compared with the general population.
Data from several studies, reviewed by Chakravarty and Genovese, have suggested that there is no increase in the overall risk of cancer in patients with RA compared with the general population. However, accumulating evidence has suggested that the RA population may be characterized by changes in the relative risk of site-specific malignancies. Consequently, the objective of this study was to review the risk of four important site-specific malignancies (lymphoma, lung, colorectal, and breast cancer) in patients with RA in the recent published literature. In particular, this review focused on observational studies comparing the incidence of malignancy in patients with RA versus the general population since these may be expected to provide a realistic perspective on risk in the clinical setting.
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