Rheumatoid arthritis (RA) that doesn’t respond adequately to conventional therapy. The definition of “refractory” RA has changed in recent years. RA was once considered refractory if it did not respond adequately to disease-modifying antirheumatic drugs (DMARDs) such as sulfasalazine (Azulfidine) or methotrexate (Rheumatrex, Trexall). Now it is usually considered refractory if it doesn’t respond adequately to a relatively new class of drugs called TNF inhibitors.
Five TNF inhibitors are now available: etanercept (Enbrel), infliximab (Remicade), adalimumab (Humira), certolizumab pegol (Cimzia), and golimumab (Simponi). These drugs block the action of tumor necrosis factor–alpha (TNF-alpha), a naturally occurring protein that promotes inflammation in the joints of people with RA. TNF inhibitors have been shown in clinical trials to work in many people with RA who had failed to respond to one or more DMARDs, and they have become standard therapy for RA. However, clinical studies have also shown that, for some people with RA, TNF inhibitors either do not have an adequate effect or have an effect at first but then lose their effectiveness.
Fortunately, there are still newer drugs that work in different ways and show promise in treating refractory RA. They include rituximab (Rituxan) and abatacept (Orencia). Rituxan works by blocking B cells, and Orencia prevents the activation of T cells. Both B cells and T cells are thought to play a part in the destructive immune process that leads to joint inflammation in people with RA. Clinical trials have shown that both Rituxan and Orencia can improve the signs and symptoms of RA in people who did not respond to either DMARDs or TNF inhibitors.