Arthritis Treatment: Should Combination Treatment Be Used for Rheumatoid Arthritis?

Rheumatoid arthritis (RA) is the most common inflammatory form of arthritis affecting almost 2 million Americans. It is a chronic, systemic, autoimmune process driven by a complex array of cells, cytokines (protein messengers), and antibodies.

What is significant is that it is a disease that affects internal organs and is associated with a marked increase in morbidity and mortality when not treated aggressively. RA is a leading cause of disability as well.

In the early 1980's, methotrexate (MTX) assumed the position of being the disease modifying anti-rheumatic drug (DMARD) of choice when treating RA. DMARDS are supposed to slow the progression of disease and multiple studies confirmed the effectiveness of MTX in doing so. Unfortunately, as effective as this drug can be, there were still many instances when patients would not respond as well as hoped or they would sustain side effects that limited the use of the drug.

Multiple combinations of DMARDS have been used to "enhance" the effectiveness of MTX. These have included MTX plus Arava, MTX plus cyclosporine, MTX plus Azulifidine, and most often MTX plus Plaquenil and Azulfidine.

A recent study (TEAR) study purportedly showed that the latter combination was as effective as MTX plus a biologic medicine. The results of this study are still being discussed among rheumatologists. The upside is that combination DMARDs are significantly cheaper than biologics. The downside is that x-ray damage appears to be worse with combination DMARD than the combination of MTX and biologic. And x-ray damage correlates with future disability.

So let's talk about biologics. The biologic revolution began in the 1990's with the introduction of drugs such as Enbrel, Remicade, and Humira, and more recently Simponi and Cimzia, along with biologic drugs with other mechanisms of action.

It has been shown in a number of studies that the combination of MTX and a biologic is superior to MTX alone. There has been a recent surge of interest in the use of monotherapy with a biologic by itself.

Nonetheless, most rheumatologists still prefer to use MTX in combination with a biologic. All biologics appear to work well in combination with MTX. The exception is Kineret which is not used much by anyone I know, because it doesn't seem to be all that effective. However, Actemra, Orencia, and Rituxan all seem to work better with MTX in combination than MTX alone.

So bottom line... MTX works pretty well for RA but it appears to work even better when combined with another medicine, preferably a biologic.