The goal of treatment is to induce remission.



In previous articles, I discussed non-steroidal anti-inflammatory drugs (NSAIDS) and disease-modifying anti-rheumatic drugs (DMARDS) and their role in rheumatoid arthritis. This article will talk about the biologic group.

Of all the advances in treatment for rheumatoid arthritis (RA), none has had a greater impact than the biologics.

Multiple randomized, double-blind, placebo-controlled trials have demonstrated the efficacy of the anti-TNF (tumor necrosis factor) agents in improving clinical symptoms and signs in patients with RA.

Patients with early RA as well as those with active RA in whom previous DMARD therapy has failed, show improvement with biologic therapy such as TNF inhibitors [including etanercept (Enbrel), infliximab (Remicade), and adalimumab (Humira)]. These agents have been shown to be beneficial when used in combination with MTX in patients with ongoing active RA despite adequate doses of methotrexate (MTX) alone. TNF-inhibitors block the effects of tumor necrosis factor which plays a major role in the perpetuation of inflammation and joint damage in RA.

Many patients improve rapidly even during the first 2 weeks. Also, there is less x-ray progression with these agents after 1 year than in patients treated with MTX alone.

In one study, the early treatment of RA with adalimumab plus methotrexate versus adalimumab alone or MTX alone demonstrated the effectiveness of aggressive MTX combined with an anti-TNF medicine versus either single drug alone with respect to clinical, functional, and x-ray outcomes.

Several studies have also demonstrated the effectiveness of these drugs in later disease as well. The TNF inhibitors adalimumab and etanercept are given subcutaneously every 1-2 weeks. The third drug, infliximab, requires intravenous infusions initially, then at 2 weeks, 6 weeks, and then every 8 weeks. In addition, it needs to be given with weekly MTX to lower the incidence of antibodies produced against infliximab. Antibody production occurs because infliximab has mouse proteins that the body recognizes as foreign. The normal immune response is then to mount a gradual antibody response to the drug.

Anakinra (Kineret) is a subcutaneously administered biologic drug that blocks a protein called interleukin (IL)-1. It needs to be given daily as a a subcutaneous injection. It also seems to work less well than the anti-TNF drugs. It should not be given along with a TNF inhibitor because of an unacceptably high rate of infection with such a combination.

Abatacept (Orencia) is a T-cell costimulation modulator. It must be given by infusion and is not indicated for same time use with anti-TNF drugs nor with anakinra. Immunizations should be avoided during and for 3 months after having stopped this drug. Also, patients with chronic obstructive pulmonary disease experience a higher rate of complications than do those on placebo.

Rituximab (Rituxan) acts through depletion of CD20+ B cells. It is useful for patients who have failed anti-TNF therapy and DMARD therapy. However, side effects include generalized mouth sores and skin rash as well as fatal infusion reactions. The infusion reaction has been seen mostly in patients who have received rituximab for treatment of non-Hodgkins lymphoma. It is much less common in patients with RA. About 80% of infusion reactions occur with the first infusion.

Several trials have shown the value of switching to a different anti-TNF agent or to abatacept or rituximab after initial TNF failure.

General precautions include the avoidance of live vaccines in any patient receiving a biologic treatment. Combinations of biologics, while intellectually appealing, have not been shown to be any more effective and have actually been shown to cause a higher rate of side effects.

For a more complete discussion of side-effects, readers are referred to another article entitled, “Doctor… what are the complications of being treated for rheumatoid arthritis with some of the drugs I've heard about?”