Robert A. Levine, MD

I think we've gone through a litany of different ideas about the drugs and how we use them. One of the concerns that many people have when anything new comes out is, is it reliable? I know, certainly, when drugs come out, is it effective, is it safe, and then can my patients get it? We ask the same questions with laboratory tests. Is it effective? Is it reliable? Can my patients get it for free or covered through insurance? With that, I think I'd like to get the last part. I'm going to hear from both of you. What advice do you have for your colleagues treating rheumatoid arthritis in the community setting? Joy?

I think we've come a long way. I think rheumatologists need to commend themselves. First of all, rheumatologists are still the subspecialty that still listens to patients. We still examine our patients. We use all of our clinical tools, we don't rely just on testing alone. However, we are probably the group of subspecialists that question and ask those questions on how this test is going to benefit our patients. And so I think that we do look at science, and the fact that we are getting these studies that are showing us consistently that looking at the signaling and whether a patient is going to have a response or not have a response to certain medications, and as we get into more precision medicine, and we see that these tools are going to help us to get our patients into low disease activity quicker and get to that treat to target quicker, I think we're going to rely on them more. Like Bob has said, it's going to take us a few years. There's going to be our early adopters that are going to look at this and look at that science and study it and say, ‘This is a tool in my toolbox, I’m going to use it with my clinical exam. I’m going to use it with all my laboratory testing, and I’m going to move into that direction quicker, and I’m going to see the response probably in my patients a little bit quicker.’ Then there are going to be the early adopters. There are going to be our colleagues that are going to take a little bit more time. But I think over the next few years you're going to see a big change in how we approach our patients. We're going to be commended for how quickly we take care of the patient journey and get these patients in low disease activity, and maybe at some point, rheumatoid arthritis will not have the stigma that it has had over the last several years, at least in my career, that this is a "crippling" disease process. Thank you.

Joy said it very nicely, and I would like to add that this technology has great potential. We're only scratching the surface based on the data on looking at the signal of nonresponse to TNFs [tumor necrosis factor], and hopefully getting more patients involved and more data collected will strengthen the argument that this is a reliable piece of information that will really help us guide therapy. Second, I look forward to the day that the adoption by CMS [Centers for Medicare & Medicaid Services] and adoption by the commercial insurance carriers will help us guide therapy and allow us to have this be an affordable option for us to use and not have the worry of large out-of-pocket expenses and concerns about that. Then, I just think that this really has the opportunity to help guide our patients to get to those treat to target goals, low disease activity, remission. That would ultimately lead to getting our patients to our goals as providers, as doctors, and also to the patient goals of improving those quality-of-life and patient-reported outcome things that we measure.

I think both of you hit the nail right on the head. We need more tools. We need more information. We need more accessibility to these tools because although we've had a tremendous explosion of therapeutic options, we haven't had any real guidance. To have a test that may guide our hand in therapy, even for just the first decision or even beyond that, because as we both and all know here, the therapy selection right now comes down to what are we most comfortable with? What came first? Maybe comorbid conditions, but mainly insurance mandates. Use this, then that, then this because that's our formulary. That's our sequence. I think many of us are feeling choked by this because as scientists, as rheumatologists, we are data-driven. We know better, and we know that as this science evolves in the 21st century, precision medicine is the way we can learn from our oncology colleagues. With that, I'd like to give a thanks to all of you for this rich and informative discussion. Before we conclude, I'd like to get final thoughts from each of you. Joy?

I wholeheartedly agree with everything that has been said here today. We're in a very rich environment that we have a lot of potential, a lot of hope, down the line by having a good collaboration with the science, with the testing, to give our patients that precision medicine that we want to achieve and to get these patients into the remittive state that they should be able to get into. By using good science and showing insurance companies that we are scientists, that we use evidence-based medicine to make some of our decisions. I hope through the work of the CRSO [Clinical Research Support Office], Bob, and my other colleagues, and I know myself I've tried to work in that area as well, that we'll be able to convince our insurance payers that this is the way to go for our patients and to get them into low disease activity in remission as quickly as possible.

I'm going to throw one out there. I'll put on my advocacy hat for a minute and just say that we've been really trying to improve formulary construction based on efficacy and safety. That flies in the face of the payers and the PBMs [pharmacy benefit managers] who basically construct formularies based on what's most profitable to them and not at all what's related to safety or effectiveness. I see this being a real tool that we can use from the advocacy standpoint in fighting the PBMs, in other words, being a PBM buster. That it could blow up their whole paradigm. I'm doubly excited, not only based on the science and how patient outcomes can be affected by utilizing this, but also utilizing it as maybe a cajole against the payers and against the PBMs who are unfortunately in control of what we prescribe and getting in the way of the doctor-patient relationship.

Well, Bob and Joy, thanks to you and our audience for this rich and informative discussion. If you enjoyed the content, please subscribe to our e-newsletters to receive upcoming peer exchanges and other great content right in your inbox.

Videos

Nehad Soloman, MD; Joy Schechtman, DO; and Robert Levin, MD, share final thoughts and takeaways on the treatment of rheumatoid arthritis in the community setting.

Clinical Pearls for RA Management

Let's get a little controversial now. We know that there's been some recent label changes with some of the targeted synthetic therapies in terms of when to use them. With this test and now potentially addressing an issue with nonresponse, where do you see yourself positioning these drugs where you have sort of some constraints now in the label where we didn't have that before? As the next iteration and the evolution of the science with this test becomes even more revealing, whether it's not just nonresponse to TNF [tumor necrosis factor] but also nonresponse to other agents or potential response to other agents. If we get pigeonholed, if you will, or directed towards a targeted synthetic and you know that they're not going to respond or minimally responsive to a TNF, how do you perceive yourself practicing at that point?

When I first saw the language and the label changes for the Janus kinase inhibitors and it was a standard class label, I was thinking of the molecular signature test. I'm saying, I've got this patient, and they've got a molecular signature of nonresponse, and yet the label on the drug, on the Janus kinase inhibitor, it doesn't matter which one, says they must fail a TNF inhibitor first before getting to be able to prescribe that medication, according to the FDA-approved label. I'm saying that really is a contradiction. Maybe they should have said a different biologic before going to one of these targeted synthetic therapies; I think that would have been much more appropriate.

We're unfortunately stuck with it, and I don't know any way to get around that. From a medical-legal standpoint, if you don't follow a label, you are liable for certain liabilities, and we all have to be cognizant of those, too. I'm not sure how to answer that conundrum, but it is a conundrum, and I see that being just maybe not completely appropriate.

Let's talk to the other side of the equation. As this test continues to evolve and more insights are given, more credence is given, how do you perceive the rheumatology community is going to either embrace or reject? We've talked about not only the heterogeneity of disease but the heterogeneity of rheumatologists and their desire to adopt early or ‘Let's wait and see,’ or just be skeptics through and through. I'm curious what your insights are.

I think as we're looking at the patient journey, it comes back to that. I think you're always going to have your early adopters of new testing and new recommendations by the American College of Rheumatology. I would say there are probably about 300 of us that are very aggressive rheumatologists that are involved in a lot of the science and understand what's going on for our patients. Then we have a middle-of-the-road, where some of those rheumatologists are very conservative, and they're going to dip their toe into the water and maybe try a few patients and see how it's going to work in those patients that they're confused about. Then you're going to have a set of rheumatologists that are probably not going to make major changes in what they're doing; they feel comfortable with where they're at, they don't read the new science. They're not precision medicine doctors and they're not going to be adopters of any of this new science. I think it's unfortunate, but patients are going to want to demand because they're going to hear about this testing. They're going to get online, they're going to know more about this testing because they like that. They look up things a lot more than you think they do. The doctors that can explain to them some of the new science and the new testing, they're going to understand those physicians are ahead of where these other physicians are. They're going to demand us being a lot more precise because these medications potentially are very expensive, number 1. Number 2, they know that this can make a difference in their overall life as far as disability and their ability to work and meet their potential in their work, with their families, and with their children. They're going to demand this because they're going to see that certain doctors are going to be more aggressive, and by showing more testing and showing them precision medicine. I think the physicians, hopefully, those who are in the middle of the road, they're just testing it, will come on board, but it may take a few years for people to adopt this precision medicine. Here at the ACR [American College of Rheumatology], we're getting together now, and I think more doctors are going to want this as well, and they're going to move along. I do think that insurance coverage, like Bob was saying, is important. We want to make sure that we take an account that our patients aren't hit with big laboratory bills. Then last of all, we must take in consideration some of the label changes in the targeted synthetics, that when we're looking at the different targeted synthetics that some of them have less risk cardiac-wise and mortality and morbidity there. Maybe we need to push on FDA to change that label to get it away from that TNF label to say any biologic and to start to look at the different targeted synthetics and know that some of them may be higher risk for cardiovascular disease than other targeted synthetics. Before this label change came about, I had patients on certain targeted synthetics, and I had the conversation with them about the new changes in the label. I documented in my notes whether they wanted to stay with that medication or come off that medication. I know there's a lot of liability there, and we have to worry about that, but we have to have those hard conversations with our patients, too.

I think that as we had mentioned and as Joy had stated so well, there are differences among doctors' adoption of new technologies. So, the question is, what does it take for those who aren't early adopters and are going to be more wait-and-see to adopt using this? One factor is just time; getting used to it, understanding it better. Maybe they haven't heard about this and don't know the data very well. Second, I just think that many of us, we're really data driven as rheumatologists, and what is the threshold of data that will convince any individual rheumatologist to adopt a new treatment or a new technology that helps guide treatment? In this case, I think the good news for this test is that more data has been coming out and the data has been consistent, that it showed good differentiation from patients with signal of nonresponse to TNF versus those who don't have the signal and is differentiating those patients in terms of their actual response. It's correlating nicely and the numbers of patients are increasing. I think that, assuming that that's going to be the case, and that the data continuously consistently shows the response that is favorable, that it will get adoption and ultimately increased utilization among rheumatologists.

I agree. I think the common theme amongst rheumatologists is to ‘Show me the data.’ We need more therapies. We need more testing. We need more information. Show me the data. Then they're provided the data, and then as we look at the data, we say, ‘Give me more data,’ and then we are provided with more data. Then it becomes, ‘Well, let me do my own little clinical trial in my N of 2 or 3, get comfortable with the utilization, whether it's of a new medication, a new therapy, a new testing, validate it for myself, even though we all know an N of 2 or 3 is a horrible number and is not the number needed to treat or number needed to make decisions, and yet somehow we find ourselves either making decisions for the rest of our life based on that first 2 or 3 patient experience positive or negative. I think that's what you're going to see moving forward.

Nehad Soloman, MD; Joy Schechtman, DO; and Robert Levin, MD, review the integration of precision medicine into the management of rheumatoid arthritis.

Adoption of Precision Medicine in Rheumatology Practices

It sounds like both of you have been using and are comfortable with the tests, and actually implementing change in therapy as a result of these results. Have you faced any challenges with insurance companies covering the test, or in the case that you described, using the test to your advantage?

I have not had any challenges as of yet in using the test. Some of this may change down the line; we don't know, but I think I just look at just trying to do the test in order to give me another tool in my databank and to also allow me to discuss what the outcomes are with insurances. I, like Bob, will write letters to the insurances and say I believe because of the testing and the precision medicine, I want to go to XYZ, and this is the reason why. I haven't really had a lot of difficulties with doing the tests and issues there, but on the other hand, in my decision-making, I think this is a good test to do, whether it's your new rheumatoid patients or patients who have been on biologics that you want to switch and then maybe you weren't doing that test at that time that you started that patient on a biologic. I think it can be used at any time, and we're looking forward to further testing and more precision medicine down the line so that we'll have a little bit more idea if we want to go to TNF [tumor necrosis factor] or a targeted synthetic. I think that we will be more precise in what we're doing to patients earlier on.

If I can add to what Joy just said. There is some concern that the patients definitely won’t want to be socked with a big bill for a test and that's not covered. We always have a discussion when I'm talking to a patient about the test that they may be responsible for a relatively small portion, but the manufacturer of the test has been very generous in terms of their assistance program and allowing us to get access to treatment or access to the results of the tests and be able to act on it. So, I know that insurance coverage is being worked on, but at this point, a lot of the patient's insurance will not cover the test. You have to mention that and tell them that if there's any problems that … we are, certainly, in my office, they bring the bill in to us, and we help them work through it with the manufacturer. We've had very satisfactory outcomes overall, and I would say that I've had no instance where some patient was stuck with an unreasonable bill that they felt was inappropriate and they didn't have disclosure.

Nehad Soloman, MD; Joy Schechtman, DO; and Robert Levin, MD, discuss barriers to rheumatoid arthritis (RA) treatment selection such as insurance access.

Insurance and Access Challenges in RA

Are you actively using this molecular signature testing in your practice? Tell us how you’re using it; when are you ordering this test, and how is it impacting your decision?

I also was a part of the AIMS [Accelerate Information of Molecular Signatures] study, and I think where this test should be used is very early on. If you have a patient on methotrexate and you know in your heart that that patient probably is going to go on to a biologic, I would get that test as early as possible. Then I would have that in my data bank, and then if that patient fails methotrexate, or their initial DMARD [disease-modifying antirheumatic drug], then I would look at, let’s look at your testing and your data, and let’s make this decision together as to what the next level should be by the mechanism of action according to what we’re seeing on the MSRC [Molecular Signature Response Classifier] test.

Let‘s say if they are a predictor to nonresponse to TNF [tumor necrosis factor], Bob, what would you choose and why would you choose it? Clearly, if they’re a predictor of nonresponse, you may stay away from TNFs, but where would you go next?

If they have a strong signal of nonresponse and the higher the number is the stronger the prediction is that they won’t respond, you’re looking at an ACR 50 of 24 weeks of about 5%-10%. I think none of us would say that that’s a good result and we think we can do a lot better. I think the key in those patients who have that signal of nonresponse, try to get an alternative MOA [mechanism of action]. It really doesn’t distinguish between the other MOAs at this point, and I know there’s research going on to look at other MOAs to try to give us a predictor of those, and I’m excited to see that data. The bottom line is to use something else. I think that we have a much better chance and it enhances the chance of getting that patient down to lose disease activity and remission on the first shot. We’re stuck due to insurance formularies. We’re restricted in our access to alternative MOAs as first-line or even second-line therapies. By the way, you don’t need to just use this in a methotrexate or traditional DMARD incomplete responder. You can use this in a biologic DMARD or even a targeted synthetic DMARD incomplete responder as a piece of data that helps you maybe pick the next therapy, whether that’s TNF or non-TNF at this point. It’s incredibly helpful ,and we’re all trying to get our patients to low disease activity and remission as directly and as efficiently and as quickly as possible to improve quality of life, improve outcomes, and improve risk of comorbidities and joint damage. This makes a whole lot of sense to me to go to something else, and we should be discussing those something else’s, and I don’t give up. Oftentimes even when there is a formulary, I look to try to appeal to the insurance company, to write letters and do a peer-to-peer with their medical director, if possible. Occasionally I’ve gotten that approved using this test to help me get the patient what I think is a better choice for them based on the science.

So, you talk about insurance companies being the villain here, and now we finally have a tool, if you will, and some data to help us be in the driver’s seat.

Drs Nehad Soloman, Joy Schechtman, and Robert Levine share their thoughts on how MSRC test results impact the treatment selection for patients with RA.

Robert A. Levine, MD

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