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Drug Tapering: An Option, Not a Necessity, for Patients With RA in Remission
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In past decades, a diagnosis of rheumatoid arthritis often signified a long-term struggle to control the disease and improve quality of life. However, in more recent years, significant advances in treatment options have enabled an increasing number of patients to achieve remission.
This evolution in the state of rheumatoid arthritis (RA) treatment has led clinicians to consider issues of tapering in patients who are in remission and wish to reduce their medication burden.
“The fact that we are having discussions about tapering now is great because it tells us we have come a long way in managing this disease,” Eric M. Ruderman, MD, professor of medicine and associate chief for clinical affairs of the Division of Rheumatology at Northwestern University, said in an interview with Healio Rheumatology. “Fifteen years ago, we were worried about how to get the disease under control, how to manage disease and how to get people into remission. The fact that we are now able to do that in a meaningful percentage of patients and we can begin to talk about tapering, is fantastic.”
Ruderman spoke with Healio Rheumatology about the circumstances that might prompt tapering, how he approaches drug tapering and how to ensure patients maintain remission of RA.
Question: When do you consider tapering in a patient with RA?
Answer: I consider it when a patient is in sustained remission. There is not a firm definition of what sustained remission is, however. Is it 1 year or is it 6 months? Nevertheless, if I have a patient who is in remission for multiple visits, then we begin to discuss tapering medications. I do not rush to taper. It is often driven by the patient.
Q: Why would a patient who is in remission want to taper? Is it an issue of tolerability?
A: It is less about tolerability and more about not wanting to take as many medications, which is a reasonable request. Occasionally, the decision to taper is related to cost; although that generally does not play into the decision because if a drug is covered, it is usually covered regardless of the amount the patient is taking.
I would also consider having the tapering discussion with a patient who has been in remission for multiple visits. However, there are two caveats. One, remission needs to be consistent. I do not want to taper drug therapy in a patient who has been doing progressively better, and it is the first visit where I think their disease is in remission. My recommendation at that point is, “Do not change anything. You are doing well, but let us wait.” Then, if it is a second or third visit and the patient is still in remission and is stable, I would begin the discussion then. The second caveat is the patient needs to be in true remission. I do not discuss tapering drugs in a patient who is in low disease or acceptable disease, but not in remission. Most of the evidence would suggest this is not going to be a successful approach.
Q: How do you define true remission?
A: That is another challenge. I use the clinical disease activity index (CDAI) in my practice largely to assess disease activity. A CDAI score of 2.9 or less would qualify as remission. I also consider how the patient is doing, how I believe he or she is doing just from talking to them and looking at them, joint counts, and swollen and tender joints. There are more formal definitions for remission that are used for clinical trials or epidemiologic studies, which are more challenging in practice because these require a sedimentation rate or a continual reassessment method. I do not always have those at the time of the visit. It is nice to use the CDAI because, at that visit, we can make a determination of how someone is doing because I have all the information in hand.
Of course, this conversation is related to more than the objective number. If a patient’s CDAI number is good, but they still feel “pretty achy,” “have to get started a little earlier in the morning than usual” or “have trouble getting to sporting events for the kids,” I may not consider tapering in those patients. It is not a huge deal, but it is enough that they are still impacted by their disease, even if their objective assessment suggests they are in remission.
Q: Once you ha ve determined that tapering is appropriate , what is the next step?
A: I usually start by tapering methotrexate, and there are many reasons for that. Typically, that is the drug the patient would prefer to taper. If there are any tolerability issues, methotrexate is likely to be the drug that is driving that.
Usually, by that point, the patient does not have tolerability issues that would mean they cannot take it at all, but they might say, “The day I take it, I just do not feel great. I know that and accept that, but I still feel kind of yucky that day.” In that case, I might try to back off slowly from methotrexate. I do not stop; I just try a lower dose to see if the patient has fewer issues with it.
However, there are exceptions when tapering methotrexate. For example, if a patient is on methotrexate and a biologic, most of these drugs work better with methotrexate than just the biologic alone.
I will taper the methotrexate down to 10 mg per week, or perhaps down to 7.5 mg per week. If the patient does well with that dose, I will usually encourage them to leave it alone and not go below that. Exceptions might be patients who are on tocilizumab (Actemra, Genentech), which tends to work better as monotherapy. Occasionally, etanercept (Enbrel, Amgen) and tofacitinib (Xeljanz, Pfizer) can also work well as monotherapy. For example, if a patient has been on methotrexate and ended up on tofacitinib with their methotrexate and is now in remission, I am generally willing to taper if they are doing well. If they had a really good response to the addition of the tofacitinib, I may suggest tapering them off the methotrexate.
Q: Do you ever taper a biologic?
A: That is not my first move. I will occasionally do that if we have gone 6 months on a lower dose of methotrexate and they are still doing well and there is a reason to taper further. If they have a high copay and are paying out of pocket or having issues getting it for a couple of months per year, we will try to stretch it. As a rule, though, if the patient is doing well and their therapy is covered, I usually do not taper. There is not a lot of evidence that would suggest that lowering the dose of a biologic decreases risk very much.
Once a patient is on the biologic, we know they have a lower risk for cardiovascular complications associated with RA, and that is an important benefit of those drugs. I am usually not in a big rush to lower them down because I do not want to lose that benefit, either. We do not know what the threshold is for that.
Q: In patients you are tapering, how do you monitor the effects of the tapering and what might prompt you to make further adjustments?
A: It is largely symptoms and exams. I will typically say, “Let us drop the dose by 5 mg a week and I will see you back in 2 [months] to 3 months and I will re-examine you.” I will see them back and reassess them and review their labs. There are situations where I might get a sedimentation rate or a C-reactive protein to see if there are systemic markers of inflammation. I am trying to taper them further, that is one more piece of data that might be helpful. If patients report they are doing a little worse, and I notice their sedimentation rate has gone up, I am going to be reluctant to suggest they taper any further at that point. I will not necessarily go up on their dose again, but I will be unlikely to taper further.
Q: Do you ever opt against tapering even in a patient who is in remission?
A: If the patient is in remission and doing well and is not having any toxicity from the medication, I am not in a rush to taper. I typically let the patient guide that because the benefit of tapering the drugs is largely in the patient’s eyes. It is the benefit of being on less medication. From a toxicity perspective, it is not clear that there is a huge benefit to tapering the drugs. In terms of the serious things we worry about, like liver toxicity and blood counts, it is not clear there is a big difference between 20 mg of methotrexate per week and 10 mg per week. If the patient is having gastrointestinal side effects and there is nausea, diarrhea or mouth sores that we think are related to methotrexate, then there may be a clear benefit to trying to taper. Symptomatic toxicities can be dose-related. But if the patient is not having any of that and is in remission and the lab tests are normal, I will not necessarily advise tapering.
If the patient brings it up, we will discuss it. However, just because the patient brings it up does not necessarily mean I am going to do it, but I am always willing to discuss it. If the patient perceives value in lowering the medication, I am willing to make a plan and try to do it; but if the patient does not see any value, I do not feel any need to push in that direction.
The recent ACR guidelines on RA management discuss tapering briefly. The guideline states you can consider tapering medication in a patient who is remission, but that it is not advisable to taper if a patient is in a low disease activity state or the disease is not as well controlled. It does not advocate for tapering; it simply says that it is something that can be considered in a patient who is in remission.
Q: Do you have any additional advice on tapering?
A: One thing I would like to mention is I do have patients who are on methotrexate monotherapy, and have managed to achieve remission on that, and I have some of them who do very well. I am more reluctant to taper their medication in that situation.
I do not know that there is a ton of data on this, but my experience has been that it is often less successful because when you increase the dose of methotrexate, you often need to go up until you hit the dose that works for that patient. It is not weight based. It is not age based. It is just something about individual patients and the dose they respond to. When we have achieved the dose that they respond to, I am especially reluctant to then begin to back off on that dose. I do not have a majorty of my patients on methotrexate monotherapy, but when I do start methotrexate, perhaps a quarter of patients will achieve remission on methotrexate alone. That is fabulous, and I would rather not lose that and then need to add another agent if that is working well. I am cautious about trying to taper in that situation. – by Jennifer Byrne
For more information:
Eric M. Ruderman, MD, can be reached at 675 N. St. Clair St., Chicago, IL 60611; email: e-ruderman@northwestern.edu.
Disclosure: Ruderman reports he receives consulting honoraia from AbbVie, Amgen, Bristol-Myers Squibb, Celltrion, Janssen, Eli Lilly, Novartis and Pfizer.