番茄社区

At the American College of Rheumatology annual meeting, new data was presented on the long-term safety and efficacy of bimekizumab (Bimzelx), a dual interleukin (IL)-17A/F inhibitor, in active psoriatic arthritis.

In this second of four exclusive episodes, 番茄社区 brought together three expert leaders in the field, all from the Cleveland Clinic -- moderator M. Elaine Husni, MD, MPH, is joined by Leonard Calabrese, DO, and Anthony Fernandez, MD, PhD -- for a virtual roundtable discussion about the potential and concerns with the newly approved drug.

Watch other videos in this series here.

Following is a transcript of their remarks:

Husni: The next set of abstracts I want to talk about is in the IL-17 inhibitor family. So very exciting, I heard about 3 weeks ago that . So Len and I are not as familiar with it since it's not approved for psoriatic arthritis yet, but I would love to talk about some of the new bimekizumab abstract data that we have found.

Fernandez: Yeah, for sure. And Elaine, this was actually FDA approved for psoriasis about a month ago, October 18th. So we now have this available to prescribe to our adult patients with moderate-to-severe psoriasis. And we've been waiting a long time for this medication to be approved. And interestingly, because we've been waiting so long, there are already papers published with several years of efficacy and safety data regarding patients in open-label extension phases of the pivotal phase III trials. And this is a medication that I think most dermatologists who treat psoriasis are very excited to use in the real world.

, the efficacy is by and large, unprecedented. It's like PASI [Psoriasis Area and Severity Index] 90 response in the 80%s at week 16 all the way out to week 52 and PASI 100 response or complete clearance of any psoriasis in 60% to 65% of patients who were treated with bimekizumab out to week 52. So we're very excited to really see if that holds true in the real world. So it's on par for sure with the IL-23s.

Husni: Yes. Wow, that's great news. So it was approved around the same time in Europe and the U.S. about 3 weeks ago.

Fernandez: I think it was approved in Europe, I think even maybe a year or two ago.

Husni: Got it.

Fernandez: But it was October 18th, it was FDA approved here. And as you can imagine, people are trying to get in front of us to give us information to hand out to patients and other literature and start using it.

Husni: Right. So Len, I know that you reviewed an , looking a little more closely on safety issues with bimekizumab and any thoughts compared to the initial IL-17 inhibitors versus the IL-17AF inhibitor?

Calabrese: Yeah, I think this abstract really...our safety data is behind the psoriasis safety data. We're contracted, we only have long-term extension up to about a year, but we're well aware of the safety profile with bimekizumab on the psoriasis side. And so this really kind of honed in on a particular subset, particularly looking at the people who were TNF [tumor necrosis factor] experienced who then went on this. So those are a little harder than de novo patients and usually carry more associated risk factors.

Just to condense this, in terms of serious adverse events, there were no surprises in terms of serious infections, MACE [major adverse cardiovascular] events, malignancies -- it looks like an IL-17 inhibitor. There is this small area, I'd like to hear Tony's take on this, and it's really not elaborately described in this literature yet, but there is about a 6% adjusted rate of candidal infections that largely -- and so that was 25 patients out of this group, which is not trivial, mild to moderate. Most people were treated and continued. Two cases discontinued this. It's not quite clear if these were just lingual or if these are oropharyngeal. And in the extant database of safety, there are a few esophageal.

So it's something that we just haven't been having our antennas up to. So Tony, what's your take on this? And I'll say -- and I think everybody's probably aware of this -- is that underlying biology IL-17 is critical and integrated host defense against fungals, and we know from inborn areas of immunity and preclinical animal models that equals fungal defense at mucus membranes.

Fernandez: Yeah, Lenny, I think exactly what you are mentioning is echoed in the psoriasis data and is definitely on the minds of any dermatologists who are going to use bimekizumab. I think in the phase III trials, roughly 10% to 15% of patients developed what was really referred to as oral candidiasis. So again, as you mentioned, a little bit unclear about really the extent of that and was it pharyngeal or not?

And similarly, as you mentioned, the way that data is portrayed in the literature, most patients were able to be treated and could continue bimekizumab, but there were some patients who discontinued bimekizumab because of that oral candidiasis. So I think that's at the forefront of our minds as we begin to use this in the real world and pay close attention to the patients who develop oral candidiasis and really see at the end of the day, is it clinically meaningful or is it just a road bump that we can treat through?

Calabrese: I think regardless, I think that clinicians who are using this drug need declarative and procedural knowledge about managing candidal infections. And I think that the literature coming out about this drug, which has not been -- I haven't seen in great detail -- needs to critically describe exactly what we're talking about. Because candida is what we now refer to as an indicator infection of suppressed host immunity. But if it's on your tongue, I don't even consider that, nor does the working definition consider that opportunistic.

On the other hand, going into the esophagus is a totally different area. So, so far I am not worried about it, but we just need more information and more education surrounding it.

Husni: Yeah. I also think it's interesting, the initial IL-17 studies had really a warning with IBD [inflammatory bowel disease], and I have to say clinically, obviously I do avoid them in people with active IBD. But I haven't seen patients kind of develop worsening IBD symptoms while they're on it. I'm just wondering what your experience has been.

Calabrese: I think that these new studies, there's channeling bias away from that because nobody's going to give to people that...

Husni: Right. Have active.

Calabrese: Yeah.

Fernandez: I know in the phase III trials for psoriasis, rare IBD cases were reported, but certainly there was no indication that blocking interleukin-17F, in addition to interleukin-17A added any risk to development or flares of IBD.

Husni: OK, great.

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