Advances in Targeted Therapy Selection in Rheumatoid Arthritis - Episode 12
Nehad Soloman, MD; Joy Schechtman, DO; and Robert Levin, MD, review the integration of precision medicine into the management of rheumatoid arthritis.
Nehad Soloman, MD: 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?
Robert Levin, MD: 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.
Joy Schechtman, DO: I agree.
Robert Levin, MD: 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.
Nehad Soloman, MD: 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.
Joy Schechtman, DO: 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.
Nehad Soloman, MD: Bob, what are your thoughts?
Robert Levin, MD: 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.
Nehad Soloman, MD: 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.
Transcript edited for clarity