Identifying the Differing Mechanisms of Available Biologics

The panel provides an understanding of the different biologics and the various mechanisms of action.

Transcript

Peter Dehnel, MD: There are some significant improvements, to your point, with treatment options. But how do I then reconcile that with the cost of those products?

Peter L. Salgo, MD: I want to get to that, and we’re going to save that little juicy morsel for later. You dove into the deep end of the pool and from a television perspective, that deep end of the pool is pronouncing these darn drug names. But there are mechanisms of action and efficacies of various biologics. I’m going to try this once and then it’s all yours, guys, because I stayed up all night practicing.

Joel Gelfand, MD, MSCE, FAAD: Let’s hear it.

Peter L. Salgo, MD: OK, we have the TNF-α [tumor necrosis factor-alpha] inhibitors. That’s etanercept, adalimumab, infliximab, and certolizumab.

Joel Gelfand, MD, MSCE, FAAD: You’re doing very well. Keep going. You’re on a roll.

Peter L. Salgo, MD: We have the IL-12/23 [interleukin-12/23] inhibitor, which is ustekinumab.

Joel Gelfand, MD, MSCE, FAAD: Very nicely done.

Peter L. Salgo, MD: I’m so excited now. We have the IL-17 inhibitors. These are the tough ones, secukinumab.

Joel Gelfand, MD, MSCE, FAAD: Yes.

Peter L. Salgo, MD: Ixekizumab?

Joel Gelfand, MD, MSCE, FAAD: Not so good.

Peter L. Salgo, MD: I’m sorry about that. Brodalumab. I think I did that fairly well. So help me out on this. What are the mechanisms of action here? How do they differ? How do you choose among them?

Joel Gelfand, MD, MSCE, FAAD: I try to explain to patients and colleagues that we have 3 basic strategies when it comes to treating psoriasis with biologics—targeted therapies to TNF [tumor necrosis factor], targeted therapies to IL-17, or targeted therapies to IL-23. That also includes ustekinumab, which is a little bit broader, blocks IL-12 and IL-23. And there are a lot of nuances that go into this. The TNFs are very effective for psoriatic arthritis. According to ACR [American College of Rheumatology] guidelines, they’re a first-line therapy if you have comorbid psoriatic arthritis, so it’s often a place where we want to use those drugs. They have more complex labeling issues. They have black box warnings for lymphoma, for demyelination, tuberculosis reactivation. Fortunately, those effects are pretty rare and uncommon. I’ve been using the drugs for 20 years and can only think of 1 or 2 patients who’ve had some of the complications, so it’s pretty well tolerated, especially using it as monotherapy, single-agent drugs.

Then you move on to the IL-17s, which tend to have a more rapid onset of action in patients, absolute efficacy. Some of them are approved for joints as well and have good efficacy in the joints. They could aggravate underlying colitis, Crohn’s disease, for example, and that’s often comorbid in some of our patients. They have shared genetics. And the IL-23s are our newer folks on the block now, and they distinguish themselves by having very strong efficacy and very strong convenience for patients. Some of these other drugs are being dosed weekly or biweekly as they’re starting on the drug and then monthly. The IL-23 inhibitors tend to be every 2 to 3 months, which is much more convenient for patients.

Peter L. Salgo, MD: If I’m a patient I want that.

Joel Gelfand, MD, MSCE, FAAD: Yes. Fewer injections. Most patients will say they’d rather have fewer shots.

Steven Feldman, MD, PhD: It’s really interesting the way the human brain works. If I tell a patient: “Would you rather have a shot every 2 weeks or every 3 months,” they’d say, “Oh, every 3 months.” If I tell a patient, “I have a great drug for you, it’s very safe, very effective, you just have to take a shot once a day.” Did I just say once a day? I’m having a senior moment. “You don’t have to do it once a day, you only have to do it every 2 weeks.” Well, then they’re like, “Oh, every 2 weeks, that’s fine, no problem.” When you give them the comparison it makes a big difference; they don’t measure the absolute value of these things very well. And you can gently guide them. Even the mechanism of action, to explain the mechanism of action to a patient. And Joel, for a physician, that was perfect. These drugs inhibit the key signaling molecules that cause psoriasis. But for a patient, I might describe it as these are all natural, organic, gluten-free anti-inhibitors that complement your natural healing mechanisms. They bring your immune system back into balance and harmony, because I like to take a holistic approach.

Peter L. Salgo, MD: Gosh, it sounds like you’re giving them pyramids and crystals to go home with.

Steven Feldman, MD, PhD: It does.

Peter L. Salgo, MD: It does. And it also is reminiscent of talking to patients who have diabetes. As we look at the literature, you want to start patients on insulin earlier, you’ve got to convince them to take a shot. And it’s how you approach it. It’s all the same.