These drugs are targeted therapies that act on tumor necrosis factor, a cytokine, to block its action in the immune response that is out of whack in patients with RA. Cytokines are chemical messengers that are produced by cells to permit signaling among each other.

TNF-inhibitors may be used in conjunction with disease modifying anti-rheumatic drugs (DMARDS) such as methotrexate, although they may also be used alone.

Since their first use approximately fifteen years ago, much information has become gleaned from clinical experience as well as clinical research trials.

About one-third of patients with RA treated with anti-TNF drugs fail to respond. This failure of response is called primary treatment failure.

And another significant percentage of patients lose response over time. This phenomenon is termed secondary treatment failure.

Patients with primary treatment failure are generally switched to another anti-TNF drug with a different mechanism of action.

Patients who experience secondary failure can have their dose of drug increased either by increasing the amount of drug given or by decreasing the interval between doses of drug.

Anti-TNF drugs do come with potential serious side effects that must be monitored for.

These include an increased risk of infection as well as a possible increase in risk of cancer reoccurrence (although this is highly speculative). TNF-inhibitors can also increase the risk of tuberculosis.In addition, an increased incidence of other fungal infections such as histoplasmosis and coccidiodomycosis has also been noted.

Other potential side effects include a risk of neurological syndromes that mimic multiple sclerosis and injection site reactions.

Options for patients who have developed failure to TNF-inhibitor treatment include switching to either abatacept (Orencia) or rituximab (Rituxan).

Abatacept acts to block the activation of T-cells which are felt to play a significant role in the immune response.

Rituximab acts by depleting B-cells, which are also felt to be a significant contributor to the role of RA progression.

Another drug that is waiting in the wings is tocilizumab (Actemra). This drug inhibits the action of interleukin-6, another cytokine that has multiple effects on the immune system. Actemra has many desirable effects but because interleukin-6 is so ubiquitous, it also has some undesirable effects as well. These include elevation of liver enzymes as well as elevation of lipids.

Other drugs that have even different mechanisms of action include the various protein kinase inhibitors such as the Syk and JAK inhibitors that are currently being studied. These drugs have multiple effects on the immune system and are attractive because unlike anti-TNF drugs, protein kinase drugs are taken orally. However, they too have potentially undesirable side effects that must be accounted for.

The current buzz is the development of biomarker profiles that will potentially allow customized therapies for RA patients. By biopsying the synovium (lining of the joint)and identifying the biomarkers that are present within the synovium, it may be possible to "customize" the correct drug or combination of drugs that will get a patient into remission.

This will provide a much more targeted approach to treatment and may potentially lead to a cure for this devastating disease.