Anti-TNF Agents and Cancer Risk: What to Tell Patients

From Medscape Rheumatology > Viewpoints Kevin Deane, MD Posted: 08/17/2011 Does Cancer That Occurs During or After Anti-Tumor Necrosis Factor Therapy Have a Worse Prognosis?: A National Assessment of Overall and Site-Specific Cancer Survival in Rheumatoid Arthritis Patients Treated With Biologic Agents Raaschou P, Simard JF, Neovius M, Askling J Arthritis Rheum. 2011;63:1812-1822 Background Shortly after the introduction of anti-tumor necrosis factor (TNF) therapies for rheumatoid arthritis (RA) and other rheumatic diseases, concern was raised that these agents might increase the risk for cancer. Complicating the issue of anti-TNF therapy and cancer risk are biologic mechanisms of TNF that, when blocked, either improve or worsen cancer risk, depending on the type of cancer. Multiple studies have examined the association between anti-TNF therapy and cancer incidence; however, to date, data on the influence of such therapy on cancer outcomes are limited. Therefore, using a large registry of Swedish patients with RA along with controls, Raaschou and colleagues investigated the effects of anti-TNF therapy on cancer staging and survival. A study of this type is possible in Sweden because cancer reporting is mandatory, and the estimated under reporting is < 5%. Study Summary Using the Swedish Patient Register, the authors identified 78,483 patients with RA, treated with or without biologic therapy (nearly all with anti-TNF agents). From this group, 8562 patients started biologic therapy during the study period. The investigators performed a matched analysis of patients with both RA and cancer who were treated with biologic therapies (n = 302, of whom 300 were treated with anti-TNF agents), matched by cancer site, age, sex, and year of cancer diagnosis in a 1:2 fashion with patients with RA and cancer who had not received biologic therapy (n = 586). Cancer stage at diagnosis was similar between groups, although a larger proportion of patients treated with biologics had stage 3 cancer (20% vs 9%) and a smaller proportion had stage 4 cancer than did biologic-naive patients (20% vs 29%). For lung cancer in particular, a greater proportion of biologic-naive patients had stage 4 cancer at diagnosis than did patients treated with biologics (60% vs 26%). Conversely, for melanoma, a greater proportion of patients treated with biologics had stage 2 cancer or higher at diagnosis than did biologic-naive patients (28% vs 0%). In the 302 biologic-treated patients, 113 (37%) deaths occurred; in the 586 biologic-naive patients, 256 (44%) deaths occurred. In adjusted analyses (including accounting for comorbid conditions), no significant differences in overall survival (relative risk 1.1, 95% confidence interval, 0.8-1.6) or survival by specific type of cancer were found between biologic-treated and biologic-naive patients. Also analyzed in an unmatched fashion were the outcomes of first cases of primary cancer in biologic-treated patients (n = 314 cancers) compared with biologic-naive patients (n = 4650 cancers). In these analyses, no significant differences in overall outcomes or cancer-specific outcomes were found between groups. The investigators concluded that cancer outcomes following anti-TNF therapy do not significantly differ, in terms of stage at presentation or survival rates, from those of biologic-naive patients with RA. Viewpoint The findings of this study suggest that the use of anti-TNF agents in patients with RA does not significantly alter cancer stage at presentation or overall survival of patients with incident cancers. However, how these results will influence the management of specific patients in terms of cancer screening approaches or use of biologic therapy after a diagnosis of cancer is still unclear. In particular, what should a rheumatologist do with anti-TNF therapy in a patient who develops cancer? Moreover, does management of biologic therapy depend on the type of cancer -- for example, should patients with lung cancer continue to receive their anti-TNF agent, and should patients with melanoma or hematologic cancers have their therapy discontinued? These questions are not readily answered by this study because most patients discontinued biologic therapy after cancer was diagnosed, and numbers of the various subtypes of cancers were limited. Furthermore, as the author of an accompanying editorial points out, it is not clear how these results apply to all patients with RA, including those in the United States who may have received anti-TNF therapy for less-aggressive disease than what is seen in Europe because of differences in prescribing practices. In terms of applicability to direct patient care, data from this study can be used to counsel patients that if they develop cancer while receiving anti-TNF therapy, the outcomes will not clearly be worse than if they discontinued therapy. However, additional surveillance studies, and perhaps controlled studies where possible, are still necessary going forward to help guide biologic use (especially anti-TNF therapy) after cancer has been diagnosed.