Newer biological agents in the treatment of rheumatoid arthritis: do the benefits outweigh the risks?

Recently, three new biological agents, rituximab, abatacept and tocilizumab, have become available for the treatment of rheumatoid arthritis (RA) in patients with active disease, who have not responded to at least one disease-modifying antirheumatic drug (DMARD). Rituximab is an anti-CD20 monoclonal antibody, abatacept modulates T-cell activation and tocilizumab is an interleukin-6 receptor antagonist. Clinical studies with these agents have demonstrated that they are effective in RA patients with moderate to active disease, who have not responded to treatment with at least one DMARD and/or tumour necrosis factor (TNF) inhibitor. Thus far, there is no convincing evidence to show that one of these three new drugs has a superior efficacy over the others or that they have other benefits compared with the TNF inhibitors. The use of rituximab, instead of another TNF inhibitor, might be an option in patients who have not responded to TNF blockade. Abatacept could also be considered, but this has not yet been formally tested. A practical advantage of tocilizumab is that it may be administered as a first-line biological agent. Adverse events, including (usually mild) infusion reactions, are common. There is a small increased risk of serious infections that appears to be similar to that with TNF inhibitors, although each drug may have its own particular risk profile. Thus far, there is no convincing evidence that the new biological agents are associated with an increased risk of malignancies. However, the number of patient-years studied is still rather limited and, hence, continuous postmarketing surveillance is necessary. Adequate studies directly comparing new biological agents with each other and with other biological agents, such as TNF inhibitors, are not available. Hence, no firm conclusions regarding the benefit-risk profile of these agents versus each other can be reached. However, the benefit for a given new biological agent currently appears to outweigh the risk for an individual RA patient with active disease, despite earlier drug treatment.