We searched the Cochrane Library, Medline, and Embase from 1995 to 2007. We used the following generic drug names as search terms: “abatacept”, “CTLA4Ig”, “rituximab”, “anti-CD20”, “tocilizumab”, “MRA”, and “anti-IL-6R”. We limited the results to randomised trials and selected studies on rheumatoid arthritis. We also searched the reference lists of articles identified by this search strategy and selected those we judged relevant. Our reference list was modified on the basis of comments
New Drug ClassNew therapies for treatment of rheumatoid arthritis
Section snippets
Pathogenesis of rheumatoid arthritis
The cause of rheumatoid arthritis remains unknown, but insights into pathogenic pathways have accumulated over the past two decades (figure 1). A plethora of cells enter the synovium via activated endothelial cells expressing various adhesion molecules. Several cell types, especially dendritic cells, express pattern-recognition molecules such as Toll-like receptors, which bind to various foreign and self structures as part of their innate immune response activity, become activated subsequently,
Assessment of disease activity and outcome
Rheumatoid arthritis is a heterogeneous disorder. Its many clinical features—differing between, and even within, individuals—make assessment of any one variable, such as joint count, morning stiffness, acute-phase response, or fatigue, unreliable for groups of patients.37, 38 Therefore, composite indices have been developed and shown to reliably indicate disease activity and response to treatment (table 1).39 American College of Rheumatology (ACR) response criteria40 are categorical in nature
Limitations of disease-modifying antirheumatic drugs, including targeted treatments
Traditionally, rheumatoid arthritis has been treated with non-steroidal anti-inflammatory drugs, glucocorticoids, and disease-modifying antirheumatic drugs (figure 2). Only disease-modifying agents—and to some extent glucocorticoids—can impede or halt the inflammatory and destructive disease processes. The most widely used small-molecule disease-modifying antirheumatic drug is methotrexate, a cornerstone of most treatment regimens for rheumatoid arthritis,58, 59, 60 with the highest retention
New classes of targeted treatments
Two new classes of biological agents have been approved for the treatment of rheumatoid arthritis—rituximab and abatacept. A third compound, tocilizumab, is in phase III trials.
Other novel agents in early trial phases
Since neither established nor new treatments—as effective as they are in various clinical situations—cure rheumatoid arthritis or remit the disease in most patients, the search for better drugs (or strategies) goes on, and various novel targets are currently being intensively studied. These include interleukins 15, 17, 18 and 32 and chemokines or chemokine receptors.34, 129, 130, 131, 132 Similarly, interference with Toll-like receptor pathways might constitute a novel approach.36, 133, 134
Recommendations and outlook
All three agents—rituximab (approved for combination therapy with methotrexate in patients with moderately to severely active rheumatoid arthritis who have had an inadequate response to disease-modifying antirheumatic drugs including TNF inhibitors), abatacept (approved in the USA for rheumatoid arthritis patients who failed any other type of disease-modifying drug and in Europe for patients who failed other disease-modifying drugs including TNF inhibitors), and tocilizumab (licensed for
Search strategy and selection criteria
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