Rheumatoid arthritis is a chronic inflammatory disorder that has no cure. It is an autoimmune disorder, in which the patient’s own immune system attacks its own tissues. The goal is to quiet this attack, and put a halt to the inflammation.
The approach to rheumatoid arthritis in this country is to begin a patient on a so-called DMARD (disease-modifying antirheumatic drug). If a patient has mild disease, then sulfasalazine is a reasonable drug to begin. However, methotrexate appears to be the DMARD of choice; this is generally used with anti-inflammatory medications such as ibuprofen. If the patient has particularly active disease, it is reasonable to use a short course of prednisone until the DMARD has a chance to fully take effect, which often is in about three months.
Virtually all of the studies of the anti-TNF alpha (tumor necrosis factor alpha) biologic agents show that these drugs are much more effective when used in combination with the so-called gold standard of rheumatoid arthritis treatment, methotrexate. In fact, Remicade should be used in combination with methotrexate. Other anti-TNF alpha drugs include Enbrel, Humira, Cimzia and Simponi.
When Should You Switch?
There are other biologic drugs commonly used, usually in the situation where a patient hasn’t responded to a drug, or has a contraindication to one of the anti-TNF alpha drugs; these include Rituxan, Orencia and Actemra. The question is: When do patient and/or rheumatologist decide that it is time to switch biologic agents? And if it is decided that a switch should be made, is the switch made to another anti-TNF alpha drug, or should Rituxan, Orencia or Actemra be the next choice?
Researchers have tried to answer some of these questions, but the studies have not been large and definitive, and thus the conclusions have not been large and definitive. One pilot study attempted to examine whether patients with an inadequate response to Enbrel responded better to Remicade; the results showed perhaps a trend toward favoring Remicade as an improvement after the switch from Enbrel, but the study was not large enough to allow a definitive conclusion. An earlier study also examined the switch from Enbrel to Remicade, and vice-versa; this study concluded that patients did benefit, and in fact did very well when switched. This study, however, also was a fairly small study, and thus cannot be considered definitive.
A Rheumatologist’s Perspective
In the practice setting, I will give a treatment three to four months before I consider a change due to a lack of effectiveness. For example, if a patient is still having disease activity after several months on methotrexate, then I will generally add an anti-TNF alpha drug. If after three to four months the patient remains with active disease, then I tend to switch the anti-TNF alpha drug to another type of biologic agent; and there are a number of choices out there. Unfortunately, science has not been able to guide the hand of the rheumatologist when it comes to such decision-making. For example, it would be nice to be able to check a simple lab test, allowing for the evaluation of, say, some sort of genetic marker that would tell a rheumatologist what type of drug to use next for a particular patient. This is important, because the drugs used for rheumatoid arthritis do have different mechanisms of action: Rituxan acts against B-cells ( a type of inflammatory cell); Orencia works on T-cells (another type of inflammatory cell); and Actemra attacks interleukin-6 (an inflammatory substance elevated in patients with rheumatoid arthritis).
At this point, it is often a matter of choosing a drug both patient and doctor feel comfortable using. But if Rituxan does not work, then the next step might be to try Actemra; or vice-versa.
So, science does not play a role in every decision; a little bit of art has its say, as does a little bit of luck.