Switching RA Medicines – Don’t Wait Too Long or Try Too Many

I’ve been on seven – count them – seven different biologic medicines since being diagnosed with rheumatoid arthritis. I started with several anti-TNF biologics and then moved to several others even bouncing back to try another anti-TNF before eventually trying Rituxan. I’ve self-injected with auto-inject pens, self-injected with needles, and seems like I’ve had every type of infusion possible. This is probably something of a record although similar stories emerge on discussion boards from time to time. With some of the biologics, I would respond for a period of time and then it would stop working. With others, there was never a response. With yet others, there would be some adverse side-effect causing cessation. This is not all to unusual as it is widely know in the rheumatology community that upwards of 30% of RA patients do not positively respond to anti-TNF biologic medicines.[1] It is important to know that there is no perfect RA treatment and every patient responds differently to medicines probably due to genetics.


Switching medicines when one doesn’t work is an important therapeutic strategy that rheumatologist and patients can use in an attempt to keep the disease at bay. In an earlier post, I discussed strategies for knowing when it may be time to switch RA treatments. In 2012, the American College of Rheumatology (ACR) published guidelines developed by an expert panel for using disease modifying (DMARD) and biologic medicines for RA.[2] These guidelines represent a revision of ones published in 2008. Revisions after only four years reflect the rapidly changing landscape of treatment options and research on treatment effectiveness. The guidelines are constructed around disease activity, disease duration, and prognosis.

The guidelines recommend starting with one DMARD upon diagnosis. If after three months of monotherapy with a DMARD, the patient is still showing disease activity, then it is recommended to move to multiple DMARDs. One option mentioned in the ACR guidelines is to try multiple DMARD therapy without biologics. This is sometimes called “triple therapy” and includes methotrexate, hydroxychloroquine (Plaquenil), and sulfasalazine. Researchers demonstrated that this triple therapy approach has been shown to be as effective as biologic treatments[3] and is certainly much cheaper. If after three months the patient still does not show improvement on multiple DMARD therapy, then the addition of a biologic is recommended starting with an anti-TNF such as Enbrel, Humira, Cimzia, Remicade, or Simponi. If after three months on the first anti-TNF biologic the patient still does not show improvement, then it is recommended to switch to another anti-TNF or a non anti-TNF. These non anti-TNFs include Orencia, Actemra, and Rituxan. If after six months there is not a positive response, then the patient can try another non anti-TNF biologic. Xeljanz has recently been approved as another treatment option. The protocol is fairly straightforward except for other factors to consider including side effects and life threatening events.

One of the important factors to be considered is to only wait three months before making an assessment about the effectiveness of each treatment. This is a fairly tight timeline and I wonder how closely this recommendation is followed. Part of this could be related to the difficultly in determining treatment effectiveness as blood tests are not always perfect predictors and patient opinions can be subjective. In my own personal experience, there were times when we would go 6 to 12 months before making a change in medications. Part of this was due to my own stubbornness and lack of willingness to admit that medicines were not working. There were times when my rheumatologist would look me in the eye and insist that it was time to make a change. There were other times when we just couldn’t be sure. The medicine might have been doing some good but probably not enough.

Another issue that researchers have found is that patients who try many anti-TNF biologics have less of a response to additional anti-TNFs and non anti-TNFs. A review of research on switching anti-TNF biologics demonstrated that patients showed a dramatic decline in response from two to three anti-TNFs. The message is that patients are more likely to fail in responding to the use of more anti-TNF biologics.[4]In a study just published in the Journal of Rheumatology, researchers found that patients who had failed a fewer number of biologic medicines did better on Rituxan (Rituxamab) than patients who had been through multiple biologics.[5] Rituxan is considered a second-line biologic to be used for patients who don’t respond to anti-TNF biologics (e.g. Enbrel, Humira, Remicade). Such results make a case for moving right into second-line treatments like Rituxan if a couple of anti-TNFs don’t work.

Based on the ACR guidelines and research on the use of multiple RA treatments, the rule of thumb appears to be to try DMARDs first, multiple DMARDs next, then one or two anti-TNFs, and finally non anti-TNFs. Cycling through more than two anti-TNFs seems to be counter productive and moving onto new treatments quickly is the best approach. In other words, don’t wait too long or try too many different treatments. The longer one waits, the more the chance of permanent damage from disease activity.

Please remember that treatment decisions should be made between a patient and doctor. Don’t stop taking any medication without talking to your doctor.

This article represents the opinions, thoughts, and experiences of the author; none of this content has been paid for by any advertiser. The RheumatoidArthritis.net team does not recommend or endorse any products or treatments discussed herein. Learn more about how we maintain editorial integrity here.
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