Ryan Haumschild, PharmD, MS, MBA: Well, speaking of clear leaders that are publishing and have been treating in the space for a while, Dr Lebwohl, you come to mind. You've done a ton of work and a ton of research. But typically, when we look at these patients, switching is something that has occurred historically among these patients as we're looking to control plaque psoriasis. I don't know if you can tell us a little bit more about how does switching occur among agents in this space and why is that clinically relevant to the treatment algorithm?

Mark Lebwohl, MD: There are many reasons why switching occurs, probably the most common is that psoriasis is a disease that waxes and wanes. If you're on a treatment that is just barely controlling the disease, patients are going to have flares. And thus, there will be good days and bad days. And when a patient’ experiences that, and you as a physician know that there are more effective treatments out there, you have to then ask yourself the question, "Why wouldn't I switch them?" And there are reasons not to switch. For example, if you are on a drug that has done a pretty good job, you stop it and then decide later you're going to go back to it. That sometimes leads to antibody formation to that drug. Thus, the drug then becomes less effective and does not remain a viable option anymore in the future. Every time you switch, you should think about that. And there are drugs for which that's a bigger problem and drugs for which that's a smaller problem. It's a particularly big problem for infliximab. Also, a big problem for adalimumab. Perhaps less of a problem for a drug like secukinumab, where the recapture rates about 95%. Similarly, brodalumab, there’s a very high recapture rate. But the bottom line is if you don't have to switch, there's some advantages to not switching. There's also a cost when you switch. Suddenly you're going from a drug that you might be giving every three months, for example, with an IL-23 blocker, and then you go to a drug where you need to start over with the loading dose. If you switch to another 23-blocker, there might be a loading dose that's 2 injections a month apart. My colleagues have already said these are very expensive treatments, so you're now increasing the cost of the treatment for that year by giving an extra dose that you didn't need before. If you look at a drug like secukinumab, which is ultimately given 2 injections, 300 mg every 4 weeks eventually. But if you now go back to secukinumab, it's 2 injections every week for 5 weeks. Thus, you're dramatically increasing the cost of that treatment. Hence, there are certainly reasons not to switch if you don't have to.

Bhavesh Shah, PharmD: I think you know what we see sometimes in the specialty pharmacy in IDN [integrated delivery network] is that there may be a factor that providers may not be aware of, is that patients may not be adherent to their medications. And that may be the driver of that switching, which may be also to your point causing for an expense, or maybe even dose optimization, where you've seen providers kind of redo the loading dose and rechallenge with a lower frequency. Thus, I think we see a lot of things as payers and claims that providers do in order to manage primary, secondary failures, which can be due to multiple reasons you mentioned, in terms of even we have biosimilars with infliximab that are also kind of lower-cost option that providers are reaching out to. Thus, there's definitely a lot of options for providers, and I feel like there's more, even more, stronger responses with some of the newer biologics that have come out from my perspective, too. It's really interesting dynamic with all the different biologics. And I think one of the things that I've noticed also is that, correct me if I'm wrong, but there are patients who will have psoriatic arthritis that develop on top of psoriasis. Thus, there's definitely certain preferred biologics that you would use because not all biologics carry that indication. I think that's another treatment decision that payers actually forget when they're making formulary decisions.

Mark Lebwohl, MD: I'm glad you mentioned that. When patients stop complying, and by the way, I didn't mention another reason for switching is a patient may have great skin, but their joints aren't doing well. And then, we've got to switch them. We've got to preserve those joints. And we spoke earlier about some of the comorbidities, and psoriatic arthritis is the most common one. 30% of patients approximately will develop psoriatic arthritis. When we stop a drug, or a patient doesn't comply, and we are not just stopping to treat their skin, we're no longer preventing the radiographic progression, a joint disease. We are no longer preventing what's happening to the coronary arteries and forgetting about the cardiovascular disease that we were protecting them against when we were treating their psoriasis. Thus, there is a real price to stopping a treatment. I think one of the things that happened when the coronavirus pandemic started is patients were nervous. They were on a drug that they know had some vague impact on their immune system, and they stopped their biologic therapies. And it turns out when you go back and look at the impact of biologic treatments on the response to COVID-19 vaccination and to COVID-19 itself, most of the treatments we use, certainly the 23-blockers and 17-blockers, don't impact the response to vaccination. And if anything, some of the drugs were protective against the advanced lung disease. They seem to block the cytokines responsible for lung destruction. And thus, the outcomes were better in the patients who continued their biologic therapy at the time before they were infected. Thus, I think we still have a lot to learn about these drugs, but certainly, the arbitrary discontinuation of them has not been good. Switching is fraught with problems unless the patients are not doing well, in which case it should be encouraged.

Robert Groves, MD: I just think this brings up another important point. Back in 1950, it took 50 years for medical knowledge to double. That's down to days or weeks now. It really is an exponential curve. Thus, knowledge management becomes incredibly important. There are lots of practitioners who are not aware of exactly what's going on in this space specific to psoriasis and certainly not specific to the combination of psoriasis and metabolic syndrome. Thus, we have to come up with strategies to help the average practitioner, who's out there delivering care, keep up with this rapidly accelerating field of knowledge. And we also have to help our colleagues in the payer system keep up with this expanding field of knowledge. It is no easy task. There really is a lot coming out. There's a lot to know. And we're getting better and better, but we're not necessarily implementing that better and better strategy broadly until we tackle the knowledge management challenge.

This transcript has been edited for clarity.