Influence of biological agents on cardiovascular disease in rheumatoid arthritis.

A wealth of studies has demonstrated that patients with rheumatoid arthritis (RA) are at increased risk of cardiovascu-lar morbidity and mortality, and that this increase is manifest early in the course of RA. 1 2 Another wealth of studies has shown the increasing effi cacy of recent therapies, or therapeutic strategies, in reducing disease activity in RA. As the infl ammatory burden in RA may partly explain the increased cardiovascular risk, can effective therapy reduce the cardio-vascular risk in RA? Unfortunately, and as indicated in the interesting report by Greenberg et al 3 in this issue of the journal (pp 576–582), 'Despite the published evidence of a heightened cardiovascular risk for patients with RA, few studies have investigated therapeutic strategies to reduce this risk.' Since cardiovascular disease makes up a considerable part of the excess burden of disease and premature mortality in RA, the clinical importance of this issue cannot be underestimated. We must therefore carefully appraise the methods and results of such studies and consider future directions. With increasing emphasis on long-term safety and disease outcomes beyond short-term EULAR DAS28 response or ACR70 we need, and are likely to see more of, studies from disease registers such as that by Greenberg et al from the CORRONA registry (reviewed in Curtis et al 4 and Zink et al). 5 However, as multiple registers address the same scientifi c question, we need to understand why results from different studies on the same topic may come out quite differently. Cardiovascular events following antitumour necrosis factor (TNF) therapy is an excellent example: the CORRONA study in this issue reports a greater than twofold reduction in cardiovascular risk for anti-TNF-treated patients compared with non-biological non-methotrexate disease-modifying antirheumatic drug (DMARD)-treated patients a fi nding contrasting with other null studies of anti-TNF. 6 – 9 They also failed to fi nd a protective effect with methotrexate, which is somewhat at odds with previous reports. 10 Transparency and harmonised reporting are key elements in this process. 11 Greenberg et al 3 should be commended for the reporting of their study, and do not leave the reader in doubt of the population under study, the defi nitions of exposure, the outcomes used, nor of their statistical approaches. Through a series of sensitivity analyses, they have challenged their own data by modifying defi nitions or analyses. In essence, Greenberg et al 3 have compared the occurrence of cardiovascular events …