Rheumatoid arthritis (RA), an autoimmune disease affecting as many as 1.5 million Americans, has been the focus of intense and fruitful research over the past two decades. A number of effective treatments for RA have been approved by the FDA for treating this disease, including a category of disease-modifying antirheumatic drugs (DMARDs) called biologic response modifiers (biologics), which are designed to halt the internal processes that cause inflammation.

While the biologic drugs currently approved for RA have shown great effectiveness in controlling inflammation and preventing the joint erosion and deformity that characterize this condition, they carry many side effects and risks, including a greater likelihood of developing serious infections. While some researchers are seeking new, more effective and safer treatments for RA, others are investigating possible causes or working to identify potential risk factors for developing the disease.

Fighting RA With Antibodies

One active area of RA research and development focuses on antibodies, proteins made by the body’s immune system that identify disease-causing agents for destruction. Several antibodies are already approved by the FDA for use in RA treatment, but new ones are being studied for effectiveness. Antibody treatments are typically given as injections or infusions.

Denosumab (Prolia) targets a molecule called RANKL, a cytokine, or protein that can play a part in RA inflammation. The first RANKL inhibitor approved by the FDA (for osteoporosis and bone-related problems in cancer), denosumab is being studied for RA use. A study published in the journal Arthritis Care & Research last spring showed the drug’s effectiveness in preventing bone erosion and improving hand bone mineral density in 56 RA patients already taking methotrexate.

, an antibody that inhibits IL-1ß, a cytokine that at high levels could trigger inflammation, is currently in Phase II clinical trials after early studies showed it was potentially effective and well tolerated as an RA treatment.

Ofatumumab (Arzerra), already approved for treating a form of leukemia, is an anti-CD20 monoclonal antibody now being studied for RA use. (Monoclonal simply means the antibody comes from a single parent cell; CD20 is a protein.) A two-part, Phase I and Phase II study showed the drug was effective in RA patients whose disease did not respond to other DMARDs.

Otelixizumab, an anti-CD3 antibody (targeting the antigen CD3), is currently in a Phase II clinical trial to study its safety and tolerability in a small group of RA patients, as well as its effectiveness compared with adalimumab (Humira). The drug is in more advanced studies as a type-1 diabetes treatment.

Clinical trials for ocrelizumab, an anti-CD20 antibody, were halted in March 2010 due to participants developing serious infections that caused several deaths.