Review of Current and Novel Treatment Pathways to Manage Plaque Psoriasis - Episode 12

Plaque Psoriasis: BE READY Trial

Published on: 

Drs Bagel and Lebwohl discuss the new biologic agent, bimekuzumab, and the data results from the phase 3 BE READY trial.

Linda F Stein Gold, MD: Mark, I want to go back, we have one newer category and we have a new biologic drug and this one falls into the IL-17 [interleukin-17] inhibition, but it’s different because it blocks both IL-17A and F. Can you tell us what that means and what’s the significance?

Mark Lebwohl, MD:Sure. For more than 10 years, we’ve known IL-17A is a critical molecule in the development of psoriasis, and blocking IL-17A, gives us profound benefits in psoriasis. But it turns out that IL-17F, though maybe not as potent a force in the development of psoriasis, does play a role. It turns out to be more prevalent in psoriatic plaques than IL-17A. And when you block both, you get an additive effect. The PASI [reduction in the Psoriasis Area and Severity Index] improvement numbers we’re seeing with bimekizumab are greater than what we see with all of the other biologics. It’s the first biologic we’ve ever had that at its primary end point achieved PASI 100 in more than half the patients. We’ve never had a drug do that before, be dramatically effective. For psoriatic arthritis, the others talk about ACR20 [20% improvement in the American College of Rheumatology criteria] as their primary end point. This one talks about ACR50. It’s more effective for arthritis and for psoriasis. It’s also incredibly fast. It’s an effective treatment for psoriasis. The dilemma that they will face is that it blocks IL-17, so effectively, there is an increase in monilial infections, but they are mild to moderate and hardly ever lead to discontinuation.

Linda F Stein Gold, MD: Mark, can you talk about that for a minute? Because when people think about monilial infections, they think about somebody who has broad immunosuppression, but this is very targeted. What should people take away from that?

Mark Lebwohl, MD:People born deficient in IL-17, and in the receptor for IL-17, so they’re effectively deficient in IL-17A, F, and the other IL-17s, those patients only get chronic mucocutaneous candidiasis. They get severe infections, which we do not see with this drug because we’re not blocking it completely. In addition, in this trial, people worry, am I going to be getting yeast infections all the time? The vast majority got it once or twice over the course of years. We are not seeing repeated monilial infections in the vast majority of patients. And again, the monilial infections were mild to moderate, not severe, and seldom led it to discontinuation. In my career, I have seen a patient with chronic mucocutaneous candidiasis, many years ago before we had fluconazole, which turns out to be highly effective and rapidly effective. In the clinical trials, and I will say for the other IL-17 blockers too, monilial infections are seldom a big problem, never in my experience, a big problem.

Linda F Stein Gold, MD: That’s good to understand what that means exactly. And the drug does have longevity, is that right? We see it maintaining effect over time.

Mark Lebwohl, MD: It maintains efficacy. And it’s also, for an IL-17, given infrequently; it’s every 4 weeks for the first 16 weeks in the trials. Then they tried an experiment thinking, well, if we reduce the frequency, it won’t do as well. It turns out that the every-8-week dosing was exactly as good as the every 4 week, even a bit better for some reason. But the point is that you can go down to every 8 weeks.

Jerry Bagel, MD, MS:Mark, I have a question for you. We didn’t see any IBD [irritable bowel syndrome] in bimekizumab, the study. Do you think that it still will be labeled within the IL-17 as a warning like the other 3?

Mark Lebwohl, MD:I don’t know; in the trial that I participated in, there were no cases. If you look at all the trials, there’s at least 1 case, but if you look at the number of patients treated, considering that Crohn disease is markedly increased in psoriasis, about 5-fold, you would’ve expected to see several, but they saw none. Now, are we saying that IL-17F blockade helps Crohn disease? We’re not there yet. It would’ve been nice if they saw no cases, then we’d say maybe it is protecting, but they did see 1 case. It doesn’t deserve the same label, but it may get it because we don’t have enough data yet to say that blocking IL-17A and F doesn’t contribute to the development of Crohn disease.

Linda F Stein Gold, MD: And that’s important so we all understand the class labeling that we might see with many of these new drugs, but it’s a really exciting time on the horizon. We have some great nonsteroidal topicals. We have a new oral TYK2 inhibitor, another new biologic agent. So we’re going to be able to improve the lives of our patients with psoriasis even better in the future.

Thank you, Mark, Jerry, and Leon for this rich and informative discussion. Thank you for watching this HCPLive® Peer Exchange. If you enjoyed the content, please subscribe to our e-newsletters to receive upcoming Peer Exchanges and other great content right in your inbox.

This transcript has been edited for clarity.