Two Valuable Treatment Advances in Rheumatoid Arthritis

Jonathan Kay, MD; Ronald F. van Vollenhoven, MD, PhD


November 25, 2015

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Jonathan Kay, MD: Hello. I am Jonathan Kay, professor of medicine and director of clinical research in the Division of Rheumatology at the University of Massachusetts Medical School and UMass Memorial Medical Center, both in Worcester, Massachusetts. I'm reporting from the 2015 American College of Rheumatology Annual Scientific Meeting in San Francisco, California. I'm here today with Professor Ronald van Vollenhoven, who is professor of clinical therapy research and chief of the Clinical Trials Unit in Rheumatology at the Karolinska Institutet in Stockholm, Sweden. Professor van Vollenhoven is also about to become professor of rheumatology at the University of Amsterdam in the Academic Medical Center and will be a welcome addition to the Dutch Rheumatology Group.

I'd like to talk to you about some really interesting work that's been going on over the past couple of years in your group. Karen Hambardzumyan and others in your group have looked at the Swedish Pharmacotherapy (SWEFOT) study and specifically at patients with early rheumatoid arthritis (RA) who did not respond to methotrexate and used the multibiomarker disease activity (MBDA) score to predict response to therapy with either infliximab plus methotrexate or triple therapy (ie, methotrexate with sulfasalazine and hydroxychloroquine). In a previous study that's been published, you've shown that a low MBDA score allows for better response to triple therapy with less radiographic progression and no need necessarily for biologic therapy.[1] You've extended that work at this meeting with a very interesting abstract.[2] Could you tell us something about it?

Ronald F. van Vollenhoven, MD, PhD: We've been interested in the question: If somebody doesn't respond to methotrexate, what do you give them next? As you know, there are some recommendations and guidelines that say that you could give them additional conventional disease-modifying antirheumatic drugs (DMARDs), so that would usually be sulfasalazine and hydroxychloroquine (Plaquenil®), and that's triple therapy, or you can go to an anti-tumor necrosis factor (TNF) agent; and, in fact, that's what many clinicians are doing if the payers will allow it. The question is if these two options are roughly equivalent or if there is a difference. Most studies show that these two options are similar, but the clinicians usually say, "No, I know that the anti-TNF agent is better." This is a bit of a paradox. What we did was we looked at these patients in the SWEFOT trial and at their MBDA score, which is also known as the Vectra® DA RA test (Crescendo Bioscience, South San Francisco, California) available in the United States. This actually tells us that if a patient is on methotrexate and they are not doing so well, but their MBDA score is high, then they really should be on an anti-TNF agent because it gives much better results. But if their MBDA score is low, and remember they are not doing so well on the methotrexate, it actually turns out that they can do very well with triple therapy, perhaps even better than with an anti-TNF agent.

Dr Kay: That was a finding that intrigued me because if it's due to the greater efficacy of the combination of infliximab plus methotrexate over triple therapy, then you would expect there to be a relatively even response in the methotrexate-inadequate responders with low MBDA scores to both treatment arms and a better response to the biologic therapy in the high-MBDA-score group. But to have a much better response to triple therapy than to biologic therapy in the low-MBDA-score population suggests something about the score that's differentiating two different types of patients. Why might this be?

Dr van Vollenhoven: I think that these treatments work against different pathways in the inflammatory process. The MBDA score identifies many different aspects of the inflammatory process, not just acute inflammation like C-reactive protein or serum amyloid A but also aspects that have to do with cartilage degeneration and vascular activation that takes place in the synovia. However, I don't know the answer to the question of the mechanism. But I can tell you this: It solves a paradox because we all have seen patients who do much better with an anti-TNF agent than with triple therapy. But we don't seem to remember seeing a patient who did very well with triple therapy but not with an anti-TNF agent. I think the reason is that we just never try it that way. We never go to an anti-TNF agent; and then, if it doesn't work, we go to triple therapy. I think we may be depriving some patients, perhaps about one quarter, who could actually do better on the triple therapy, so we need to keep this in mind, and maybe MBDA will help us decide for which patients to use triple therapy.

Dr Kay: Your group's work has really set up a new paradigm in the use of this blood test, MBDA, that really predicts which patients don't need biologic therapy to prevent structural damage from occurring and which patients might actually do better clinically if treated with one type of therapy as opposed to the other. This is very interesting and has great implications for clinical practice.

Also presented at this meeting was a study from George Schett's group in Erlangen, Germany, where they looked at the ability to taper DMARD therapy in patients with RA in remission on treatment.[3] They measured MBDA at baseline while the patient was in remission, and they found that patients with a score of less than 30 (ie, the typical cutoff for low disease activity) were able to sustain remission off of the DMARD therapy as compared with those with higher scores who had a greater risk for relapse. Now how does this fit in with the work that you've been doing?

Dr van Vollenhoven: That was a terrific study from our colleagues in Germany. They had done this study called Reduction of Therapy in Patients With Rheumatoid Arthritis in Ongoing Remission (RETRO),[4] but actually there was nothing "retro" about it, as it was really forward thinking. The name is wrong, but it was a great study. They showed that if you have patients who are doing well on whatever treatment (eg, biologics, conventional DMARDs, steroids), you are mostly able to reduce the intensity, cut the dosages, reduce the dosing frequency, or maybe even stop it. These results were already very interesting and have been published. At this meeting, they showed that you can then use MBDA score to know upfront in which patients this strategy is most likely to work. This is true especially if you combine MBDA and anticitrullinated protein antibody status. With this information, you can say for a given patient that you will either be very hard-pressed to take them off treatment because they will flare or that they're doing so well that you can try to stop treatment and will most likely succeed.

Dr Kay: This body of work looking at a biomarker panel is really starting to help us provide personalized medicine, targeting specific therapy for the specific patient. Thank you very much for your insight, and I look forward to seeing more of this work coming out of Amsterdam.

Dr van Vollenhoven: Thank you, Jon.

Dr Kay: Thank you for joining us today, and I look forward to seeing you again on Medscape.


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