Rheumatoid arthritis is the most common inflammatory form of arthritis. It is a systemic autoimmune disorder for which there is yet a cure.

Because of its devastating effect on both joints as well as internal organs, it has a substantial impact on both an individual's ability to function as well as their expected lifespan.

In addition there is a significant negative economic impact on society because of the disability it causes.

While there is no known cure, newer biologic therapies have enabled rheumatologists to help their patients achieve remission. The effectiveness of the TNF inhibitors, the first group of biologic therapies to enter the market, has been established in multiple randomized clinical trials.

Unfortunately, many patients who start TNF therapy discontinue it because of three major reasons: side effects, lack of initial response (primary failure), or eventual loss of response (secondary failure).

So what can be done? Options include switching to another TNF inhibitor or going to an alternative biologic group or going backwards and using standard disease modifying therapies which, in my opinion, are not nearly as effective.

There is a question whether switching TNF inhibitors makes sense when a patient fails to respond or loses response to the initial TNF inhibitor. There may be a genetic predisposition to non-response so that a patient may not respond to these drugs as a class. However, there has also been substantial anecdotal empirical evidence that switching TNF inhibitors does work and is a viable option for patients.

A recent meta-analysis published in Medscape (The Effectiveness of Anti-TNF-α Therapies when Used Sequentially in Rheumatoid Arthritis Patients: A Systematic Review and Meta-analysis. Suzanne Lloyd; Sylwia Bujkiewicz; Allan J. Wailoo; Alex J. Sutton; David Scott) addressed this issue.

The gist of what they found is that patients who fail one TNF inhibitor may still benefit from switching to another TNF inhibitor. What they found also, though, was that the response rate in patients using a second TNF inhibitor was less.

They concluded that more evidence is needed to elucidate the effectiveness of switching.

They also concluded that there was a degree of selection bias since patients who fail a TNF inhibitor will have a worse prognosis and are unlikely to show a good response to any treatment.

While there have been a number of studies that have tried to look at this problem, they have all been flawed as a result of one reason or another. Nonetheless, after examining all the data, these authors reached a final conclusion that rheumatoid arthritis patients who fail to respond to one TNF inhibitor will show a significant response to a second drug of that class.

I, personally, feel that using a second TNF inhibitor is worth trying. Yes, the response may not be quite as good, but if the patient does get a good effect, then both the patient and I feel more comfortable with it. Biologic drugs are scary enough without the thought of having to go to an entirely new class of medicines.

What is not known is this: is there a sequence that TNF inhibitors should be used in that is most effective and that makes sense? Knowing the answer to this question might help a lot with decision making.

Also, the advantage of switching TNF inhibitors versus going with another biologic group such as drugs that affect B-lymphocytes, like rituximab (Rituxan), T-cells, like abatacept (Orencia), or interleukin-6, like tociluzimab (Actemra), is not clear.

Stay tuned for further developments!