The combination of methotrexate and tumor necrosis factor (TNF) inhibitors have been the gold standard for inducing remission in patients with rheumatoid arthritis. But this combination does not always work. This article provides information on alternatives.

Rheumatoid arthritis (RA) is the most common inflammatory form of arthritis and affects more than 2 million Americans.

It is a chronic, progressive, autoimmune disease that causes both joint damage as well as harm to internal organs.

While biologic drugs, first introduced about 17 years ago have been a boon for RA sufferers, not everyone responds. Some people have no amelioration of their symptoms (primary non response) and others lose their response over time (secondary non response). And others develop side effects or frequent infections that limit the usefulness of biologic therapy.

Fortunately, there are alternatives.

The first is tocilizumab (Actmera). This is a medicine that blocks the effects of interleukin 6, a protein that plays a pivotal role in the progress of RA. This drug is a good option for those patients who fail TNF therapy. Unlike the many TNF inhibitors, Actemra can only be given intravenously as of this writing … but a subcutaneous form is in the works.

Another option is abatacept (Orencia.) This blocks the activation of T cells which are cells that also play an important role in chronic inflammation. Orencia is also given intravenously … but like Actemra, a subcutaneous form is available.

Another second line biologic is rituximab (Rituxan). This is a drug that depletes B cells, another pivotal player in the RA process.

As one might imagine, tinkering with the immune system has its downsides and the number of potential side effects associated with biologics is prodigious. However, in experienced hands, in other words, in the hands of an arthritis expert, the likelihood of a significant problem can usually either be avoided or at least recognized. Nonetheless, these drugs do carry potential risks that should be explained to the patient and risk versus benefit needs to be discussed.

Some people have advocated combining biologics with different modes of action to see if better control can be achieved. Unfortunately, it appears this strategy does not work. One study used a combination of a TNF inhibitor along with Orencia. No improvement in symptoms and signs of disease were seen. What was not noticed was an increased incidence of side effects.

Newer drugs that target different proteins and cells are constantly being evaluated. Inhibitors of a chemical messenger called tyrosine kinase have been evaluated. One such drug, a JAK kinase inhibitor, appears promising. The drug, tofacitinib, has looked promising in clinical trials. The advantage of this group of medicines is that they are oral.

Other companies are also exploring this pathway and developing competitiveness products.

The ultimate goal, of course, is remission!