Mark G. Lebwohl, MD, and Joseph F. Merola, MD, MMSc, discuss different head-to-head studies in psoriasis.
Mark G. Lebwohl, MD: We already broached the treatments. I assume that you have the same treatment paradigms I do, which are TNF blockers [tumor necrosis factor], IL-17 blockers [Interleukin-17], and JAK [Janus kinase] inhibitors. There are no head-to-head studies between those except for the TNF and the IL-17 blockers, which appear to be fairly similar actually, there are JAK inhibitor studies against adalimumab. What would you say about those?
Joseph F. Merola, MD, MMSc: At a high level, I think we are very fortunate in dermatology to have so many head-to-head studies in psoriasis where we really can be so data-driven about where we went ahead with the psoriasis patient. In psoriatic arthritis [PsA] as Mark already nicely alluded to, we have fewer head-to-head studies. The ones we do have are in the IL-17 vs TNF camp. Let me say, putting the rheumatology hat on and again, at a very high level, TNFs have been a mainstay of therapy for psoriatic arthritis. They have remained such first-line therapy and many of our recommendations.
I was part of the ACR [American College of Rheumatology] guidelines many years ago, which have now become a bit dated but really putting those TNF agents at the front line. Those head-to-head studies with IL-17s, I think, have really shown us that they are as good as anti-TNFs in terms of the domains of psoriatic arthritis, but I think that they are better with skin efficacy in those patients with psoriatic arthritis with skin disease. That in my mind puts them in the first-line camp for our patients with psoriatic arthritis. They've shown radiographic inhibition data as well as very fine axial data in psoriatic axial disease as well, so very robust data.
When we talk about IL-23 [Interleukin-23] inhibition in that camp, we also have very good psoriatic arthritis data in many domains, although, it falls a bit short when it comes to axial data and so we're waiting to find out if there may be something there in the axial compartment with IL23 inhibition. It falls a little bit short when it comes to inhibition of radiographic progression data for that phenotype of patients where they maybe have a higher risk of erosive disease or have no erosive disease or present damage. I think there's a little more nuance and Mark mentioned as well, JAK inhibition where we have very robust data in psoriatic arthritis across multiple domains. In fact, just recently we have approvals in ankylosing spondylitis of a couple of our JAK inhibitors where we can, again, rest a little more in the fact that those are probably treating some of the axial or potential axial disease in our patients with psoriatic arthritis. We have less robust skin data there, but Mark was alluding to 1 of the upadacitinib studies where they had an active comparator arm of adalimumab that showed very impressive both skin and joint disease improvement adjacent to an adalimumab active comparator that also showed good efficacy there. I think we won't probably get into a nuance of safety and such now, but I think from an efficacy standpoint, it certainly showed some good data.
I think in most rheumatologists' minds, anti-TNF is very much at the forefront across the full breadth of domains of disease. We didn't get to talk a lot about comorbidities, but when we talk about some of the nuances here, when we talk about the potential for 5% or so of our patients with psoriatic arthritis disease potentially to have IBD [inflammatory bowel disease], to have uveitis or other things, there we know that anti-TNF really stands out as a mechanism that treats across the full breadth of domains of disease, but also comorbidities of disease here. I think that's a place where it really has remained at the forefront again, as have many of our frontline therapies, IL-17, and such. Hopefully, Mark, that covers what you were hoping for in that question.
Mark G. Lebwohl, MD: Yes. I'm glad that you mentioned comorbidities because patients come to us, and they have many other conditions that really ought to impact our selection of therapy, and they do. I'll just tell you a story. Shivani B Kaushik and I published an article in 2018 called “Which Therapy for Which Patient: Psoriasis Comorbidities and Preferring Systemic Agents.” I went through a long list of comorbidities that psoriasis patients have. After that article was written, I actually was asked by the National Psoriasis Foundation to give a talk to a room of 107 patients with psoriasis and psoriatic arthritis. At the beginning of the lecture, I said, “I want everyone in the room to stand up. I'm going to read a list of conditions. Don't sit down when I call it out because I don't want to embarrass anyone, but if I call out something that you've had at the end, I'm going to ask you to sit down.” Out of 107 people, we asked about joint pain, joint swelling, and arthritis. We asked about cardiovascular respect, smoking cigarettes, diabetes, hypertension, hypercholesterolemia, family history of heart disease, or personal history of heart disease. We asked about a history of cancer. We asked about HIV [human immunodeficiency virus], hepatitis B, hepatitis C, lupus, demyelinating disease, and a bunch of other things. We also asked if the patients are obese, which impacts your selection of therapy. At the end of my reading of that list, I asked the patients if I called out something that affects them, then please sit down. Out of 107 people, 1 was left standing.
Joseph F. Merola, MD, MMSc: One skinny young guy.
Mark G. Lebwohl, MD: That's right. You're exactly right. One skinny young guy.
Joseph F. Merola, MD, MMSc: To your point, the safety of these is it's so important now that we have even all these targeted mechanisms because patients have these comorbidities and I like to reassure them. In a condition like psoriatic disease where there are so many comorbidities, I can sleep at night having conversations about all these mechanisms with my patients as you're alluding to. The safety profile is really overall tremendous, but I think we may get into a little bit of the nuance of certain comorbidities here, to your point.
Mark G. Lebwohl, MD: Indeed, if a patient comes to me and they've had a very strong history of heart disease, and I'm worried, are they going to go on and develop a myocardial infarction? We know from the work Joel Gelfand MD, MSCE, dermatologist at Penn Medicine, Philadelphia, Pennsylvania’s, done with Nehal Mehta MD, MSCE, director of the Inflammatory Risk Clinic, Preventive Cardiology, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania that there is a marked increase in cardiac risk and risk of heart attacks in patients with psoriasis. When I get that history, the TNF blockers have the best evidence to date that they prevent heart attacks. Most of that is registry data.
There are multiple registries, and all of them show about a 50% reduction in heart attacks from TNF blockers, so those become a treatment of choice for me. Now, if you looked at malignancy, particularly skin cancers, somebody who has had a lot of squamous cells, probably TNF blockers would not be my first choice because of the increased risk of squamous cells with patients on TNF blockers. If we looked at pregnancy, we have 1 drug that doesn't cross the placenta and that's certolizumab pegol. Because it's pegylated it doesn't get into breast milk, it doesn't cross the placenta. In young women who are planning to have children, that might be a treatment of choice, and I have often used it in that setting. I assume that when you look at patients, you will consider that as well. We know, for example, TNF blockers are used with patients with hepatitis B surface antigen positivity. That's a real risk for reactivating hepatitis B more than with some of the other drugs.
Joseph F. Merola, MD, MMSc: And TB [tuberculosis]. I know you and I have had this conversation. Again, probably avoiding some mechanisms of others, maybe less so anti-TNF in that context. Those are wonderful examples. I wonder if I might mention as well, I think the axial piece, which we didn't unpack in great depth that is a unique one, but it's a very important one. Again, just to highlight that they're … now the 3 treatments of choice there, NSAIDs [nonsteroidal anti-inflammatory drugs] aside, because certainly many rheumatologists, ankylosing spondylitis might start with NSAIDs, but anti-TNFs, IL-17 inhibition, and now JAK inhibition. Those are really the only ones we can look at for that particular disease. It's probably worth highlighting as a point so here we are.
Transcript edited for clarity