Peter Salgo, MD: Before we leave this topic, give me some feedback from patients who’ve actually navigated this whole framework, and are on the CGRPR [calcitonin gene-related peptide receptor] antagonists. What’s life like for them?
Shoshana Lipson: We’re seeing a very mixed bag. My group has about 6500 people in it. It’s not the biggest migraine group, but it’s almost the biggest CGRP group. We’re having all sorts of experiences along the spectrum—from people who actually received the medication in a timely manner and have found that they are responding 50% percent or more so—they’re relatively happy. And there are people who are saying, “If this is life changing, I’m getting my life back. It’s phenomenal; it’s a miracle drug. I can do math again. I can go back to work. I can actually play with my child.” So that is on the positive side of the spectrum.
All the way on the side of the spectrum, we’re finding that patients are feeling a lot of concern about the way the clinical trials were structured. There is a sense that the population using the clinical trials was not fully representative of the real-world migraine population. There is a sense among patients that they’re being left out of the conversation, in how these medications are actually working in the real world. There’s kind of a fear and anxiety. And then there [are] all the people in between, especially the ones who say, “Well, I got 50% better, but I still have 15 migraine days a month. So what do I do now? Do I try a different medication?” Or they’re concerned because of the layering issue, which is where—let’s say they were taking Botox and now they’ve been told, “You can’t have Botox and a CGRP inhibitor,” so they’re being taken off Botox, which can have devastating impacts.
Stephen Silberstein, MD: And they crash.
Shoshana Lipson: And they crash, exactly.
Stephen Silberstein, MD: Here’s an interesting problem. With cheap drugs, you can combine as many as you want. With expensive drugs, suddenly, you can’t. There’s theoretical and scientific evidence that the best combination treatment would be Botox and antibody. Botox works with 1 set of fibers. The antibodies work on a different set of fibers. Basically, our paradigm is our failures, the Botox failures. We add the antibody to Botox, and eventually we’ll know what happened, and we can discontinue the Botox. But the companies say, “Well, they haven’t been tested, and therefore, you can’t approve both of them.” But I can tell you, 90% of the combinations—that will be used that are approved—have never been tested. There’s no evidence for it, yet we’re allowed to use it. Now, what I’m really stating is the fact that the criteria come from cost, not from science.
Peter Salgo, MD: There [are] a lot of folks who’ve said to me, “I love evidence-based medicine, and as soon as I get some evidence, I’d be happy to use it.” But there’s a lot of stuff out there that has not been studied adequately long term, and yet these patients are suffering. And if you restrict your dispensing to patients, who absolutely meet the evidence-based criteria, you’re going to be leaving a lot of her friends out in the cold.
Maria Lopes, MD, MS: Well, you know for us there’s evidence, right? There’s published literature that supports the combination use. One of the criteria for use of CGRPs is that there’s a washout period with respect to Botox.
Stephen Silberstein, MD: Why?
Maria Lopes, MD, MS: Well, perhaps because that’s how the clinical trials were designed?
Stephen Silberstein, MD: They weren’t. Here’s the problem with that. If you wash out Botox and the patients crash, they will wind up being hospitalized. We use CGRP in the presence of Botox, often, because we can get a sample. Then if they do well, we’ll move them along to prescription Botox.
There’s absolutely no reason in the world that you have to wash it out. That was done for a clinical trial to prove the fact that it was the same for any other prevention. All the studies,demanded no concomitant prevention. Does that mean—if you’re into topiramate—you have to wash topiramate out before you go on that? It was for statistical separation. The only trial that allowed a concomitant drug was TEVA, and they allowed topiramate. To our surprise—topiramate worked—the antibodies worked just as well whether or not the topiramate was present.
Therefore, we have good scientific evidence. At least for topiramate, they were synergistic. The costs of these trials are enormous. To design a trial—with or without Botox, with or without placebo, with or without active drug—would be $100 million. So I think the only way we can do it is real life.
Maria Lopes, MD, MS: It would be real world. It would be meta-analysis. But if there’s published literature, I think that helps at getting us to agree rather than disagree.
Stephen Silberstein, MD: I’m not disagreeing with you, but there’s no scientific basis except for bad trial design, which was based to get FDA approval and has nothing to do with real life. Let me assume for the sake of argument, you had AIDS and you were on an anti-HIV medicine. If a new one came along, would you stop all the drugs before you got it? Even though there is no scientific evidence that it was studied that way? So why do it for migraines? Because it’s a second-rate disorder, right, unless you’ve had it.
Maria Lopes, MD, MS: When you’re talking about high-cost drugs and you’re looking at the literature to support it—for efficacy and for safety—usually there’s a moment to educate us.
Stephen Silberstein, MD: I’m not disagreeing with you. What I’m really stating is there are different criteria based on your perception of how bad the disorder is. It’s like the devil quotes scripture for his own benefit.
My problem is taking an aspect of trial design that had no concomitant medication. Why? With the belief being that if you’re on a drug, it would blunt the effect. That’s why it was done. It’s been shown that it’s synergistic with topiramate, and the trials that are now going to be done show that they’re synergistic with CGRP antagonists. The reason they weren’t done before is—we didn’t know while we were doing the trials—if they were better or worse, and what would happen. Trials are like science experiments, they’re not real life. I would take objection to saying—I can agree that you wouldn’t pay for both, but the washout to me is brutal.