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Clinical trials of combination therapy in persistently active rheumatoid arthritis in adults

James R O'Dell, MD
Section Editor
Ravinder N Maini, BA, MB BChir, FRCP, FMedSci, FRS
Deputy Editor
Paul L Romain, MD


Patients with rheumatoid arthritis (RA) and persistently active disease despite initial pharmacologic therapies require adjustments in their treatment regimen to achieve effective disease control. The use of combinations of disease-modifying antirheumatic drugs (DMARDs) is typically required in patients with persistently active disease, defined as RA of at least six months’ duration which remains active despite initial treatment with one or several DMARDs [1].

DMARDs are divided into two broad major categories, nonbiologic and biologic, and a third category of drugs with some features of each of the major types.

The nonbiologic DMARDs are traditional small-molecule or synthetic DMARDs, such as methotrexate, leflunomide, sulfasalazine, and hydroxychloroquine.

The biologic DMARDs, produced by recombinant deoxyribonucleic acid (DNA) technology, usually target specific cytokines or their receptors, such as tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, or IL-6 receptors. Other types of biologic DMARDs include B-cell depleting agents and T-cell costimulatory blockers. The use of biologic DMARDs has been referred to as “targeted therapy.”

A third category of DMARDs includes the drug tofacitinib, which shares some features with the nonbiologic DMARDs as an orally active small molecule drug but is an inhibitor of isoforms of the Janus kinases, which are cytoplasmic protein tyrosine kinases that are critical for signal transduction from plasma membrane receptors for a number of different interleukins. Janus kinase inhibition by this agent has biologic and clinical effects similar to the biologic agents.


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Literature review current through: Sep 2016. | This topic last updated: Jan 2, 2016.
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