Peter L. Salgo, MD: OK. Now, you’ve all been using biologics. What’s your impression as a general group? Are you impressed with them? Do they work? Are they the next big thing? Are they the present big thing?
Linda S. Cox, MD, FAAAAI, FACAAI, FACP: I think that they’ve been a game changer for a patient population that has driven us, or was driving us, crazy. They’d be in our office every other week. We can never get them off oral steroids. They’re going to the ED [emergency department] getting antibiotics for sinus infections they don’t have. And because, as John said earlier, we’re physicians and we want people to get better, it’s just when you see that patient’s name on the appointment book, or you get that call at night, you’re like, “Oh, what more can I think of?”
Louis Christos, RPh: My question is: Are we seeing real-world evidence that mirrors what we’ve seen in the clinical trials?
John J. Oppenheimer, MD: I think Don hit it, though. There is a subgroup that’s just remarkable. They stop all their medicines. You can beg them to take their medicines. There are other people who need to be on their medicines, and there’s still a subgroup who doesn’t respond as well as you’d like.
Don A. Bukstein, MD: And you’re absolutely right. I like your point. The point is that these patients need to be monitored. They need to be seen back frequently. Because in the best world, there are going to be two-thirds of them who do really well, but there are going to be 20% or 30% who don’t respond to that biologic. And it’s craziness to keep them on something they’re not responding to. The response in this disease with these biologics usually is very rapid.
Linda S. Cox, MD, FAAAAI, FACAAI, FACP: Can I just bring in 1 point? We keep talking about clinical trials. Who is included in clinical trials? Compliant patients? They have to be stable enough to get included. They’re not real-life patients. Your primary outcomes.
Peter L. Salgo, MD: Well, that was his point.
Linda S. Cox, MD, FAAAAI, FACAAI, FACP: Severe exacerbations, reduction by 1.3%.
Louis Christos, RPh: My whole point is, could we have data for noncompliant real-world patients showing that 50% reduction in exacerbation, or are you seeing only 20% because they’re not compliant on their standard of care?
Peter L. Salgo, MD: In the view of the payer, what is the place of biologics? They’re expensive. Who gets them? Who needs them? When do you approve them?
Louis Christos, RPh: Based on the data we have now, the right patient is the patient who was studied in the trials, similar to what was done in the trials.
Peter L. Salgo, MD: But they’re not the typical patient; that was your point in the first place.
Louis Christos, RPh: But the hypertensive medications are never the typical patient either.
Linda S. Cox, MD, FAAAAI, FACAAI, FACP: But these are patients who go to the ED. They go to multiple urgent care clinics. They get multiple x-rays.
Louis Christos, RPh: Well, you’re proving my point. So these patients—if you give them a biologic, are you going to change that?
Linda S. Cox, MD, FAAAAI, FACAAI, FACP: Yes.
Louis Christos, RPh: All of them?
Linda S. Cox, MD, FAAAAI, FACAAI, FACP: No, never. In medical school, the wrong answer is “always never” or “always.”
Louis Christos, RPh: That’s why we have to limit it initially now because we don’t have the data to identify the real-world patients who will benefit from these therapies and the ones who don’t. As you brought up, it makes no sense to allow this for a noncompliant patient who’s not going to be compliant.
Linda S. Cox, MD, FAAAAI, FACAAI, FACP: But you’ve got some data. They can look at all the cost involved in that patient’s care.
Don A. Bukstein, MD: But you’re absolutely right. So you have to demand that patient be monitored appropriately. I remember when I was looking over claims for a major insurer, I’d find some. The only thing in the chart was “patient better.” I mean, a biologic that’s costing up to $30,000 a year, that’s not enough. And so I think there are certain ways to follow these patients. There are certain markers, whether it’s eNO [exhaled nitric oxide], whether it’s an asthma control test, symptom scores, beta agonist use, workdays, quality of life. I could go on and on about the multiple outcomes that you can follow in asthma, but when you’re really that sick, necessitating that form of therapy that is very expensive, we probably should demand more in the way of better outcome and follow-up.
John J. Oppenheimer, MD: But at the end of the day, I can’t speak with any robust data to separate one for another. I will say there was a beautiful editorial in the New England Journal that said that these need to be done head-to-head. The problem is the expense of doing it would be mind-boggling.
Louis Christos, RPh: You’re not going to see that.
John J. Oppenheimer, MD: I don’t think so either. But the truth is that we’re really left trying to tease these studies out, and everybody can argue why one is better than the other.
Don A. Bukstein, MD: But what it has done, too, is usher in a whole new era. It’s pretty exciting.
John J. Oppenheimer, MD: It is.
Don A. Bukstein, MD: Because we have these agents, we’re understanding all the different phenotypes. We’re kind of going at it maybe backward; we’re having therapy that interrupts pathways, so we see what happens in the end result, so we can relate that to a clinical outcome. That’s called translational medicine. And that’s really big. It’s precision medicine with regard to treatment, but translational medicine, understanding and going back and then seeing what it may be. Our ultimate goal is to, for every phenotype, relate that back to an endotype that has a physiologic change that generates that.
John J. Oppenheimer, MD: Well, for the clinician, it’s the right medicine at the right time for the right person, and that’s where we are. That’s what’s so exciting. We finally—I mean, we gave and held steroids and oral steroids for generations, right? Let’s be honest. And now we’re talking about understanding subparts of these mechanisms and really attacking them.
We’re all talking about pathways, and there’s this pathway and that pathway, and this drug that affects that pathway. Is there a pathway? Is there a final common pathway and a drug that hits that pathway?
Don A. Bukstein, MD: I’m very doubtful. Because the one thing I’ve learned as I’ve gotten older is that the human body has this redundancy to it. And it has so many ways of getting where it wants to go. Usually to the benefit of us but sometimes not. And here we’re talking about inflammation. I think maybe we’re talking too much about pathways because one of the biggest difficulties I find is not that there’s too much inflammation but too little communication. So it’s not necessarily just a disease of inflammation but communication.
Peter L. Salgo, MD: When you say communication, let me be very clear, is this cellular communication or physician—patient communication?
Don A. Bukstein, MD: Oh, no—physician—patient communication.
John J. Oppenheimer, MD: Thanks for clarifying that.
Peter L. Salgo, MD: But the reason I ask is that if you are interrupting cellular communication, isn’t that what these biologics are doing?
Don A. Bukstein, MD: Yeah.
John J. Oppenheimer, MD: But Don brings up a good point. I mean, part of the problem, and we need to get back to this, a really neat study shows that many of the people who we have on biologics didn’t take their more standard therapy before. We need to understand why. Was it a communication issue? Was it a lack-of-efficacy issue? These are some of the things we have to go back and resolve.
But also, in answer to your question, Peter, we have newer therapies that we call upstream. So there’s TSLP [thymic stromal lymphopoietin] and IL-33. We’re going to have to come back and have another conference on that one because we don’t have enough data other than 1 initial study.