Safety Profile of Biologic Therapy for Plaque Psoriasis

Brad Glick, DO, MPH: You mentioned adverse effects; George mentioned adverse effects of TNF [tumor necrosis factor] inhibitors in discussing mechanism. Those tend to go hand in hand. Comment on in general, and then I can pass this over to our other colleagues, just looking at biologics, we’ve talked about TNF, interleukin [IL]-12/23 and IL-23 blockers and IL-17s. What about in comparison to our traditional systemic agents? Have we done better in terms of adverse effect profiles, or are these drugs comparable to our prior agents? Erin, what are your thoughts? Then, I will pass it over to Neal and George.

Erin Boh, MD, PhD, FAAD: I think that these biologics are worlds ahead in terms of safety in that they are very safe. We do not have the end-organ toxicity or the cytotoxicity that we see with traditional agents such as methotrexate, cyclosporin, and acitretin. These drugs, I think, should be first line for all patients with psoriasis, psoriatic arthritis, and other comorbidities. Getting them is a whole different story. We do not have much control over that. In terms of safety, I tell patients, if you are going to be in for the long haul, and psoriasis is forever—that is the first thing that I tell every new patient who comes in and I diagnosis their psoriasis, and even if I do not—I tell them psoriasis is forever. You need to have comfort in the drugs that you pick. While we do not have 50 years of experience like we might have with methotrexate, we have good, solid long-term data, especially with the TNF class. We have 20-plus years, and we have 10, 15 years anecdotally with some of the other ones. I think, as a class, overall, all biologics are way safer. There is less monitoring with laboratory work. In the end, I think not only will they be more efficacious, they are going to really be cost effective because they work so much better than the traditional agents.

Brad Glick, DO, MPH: George, when do you consider initiating biologic therapies as first-line therapy?

George Han, MD, PhD: I think, just to Dr Boh’s point, these medicines are overall very safe and effective. You think about the tradeoffs, and everything in life has a risk-benefit analysis. You think about it, I am running late for work. Do I run across the street or risk getting hit by a car? How much will my boss yell at me? Everything has a risk-benefit analysis. When you look at the risks of these biologics, you look at the label. On all of them it says, “may increase the risk of infection” and the stuff about vaccines. Then they list everything that is numerically higher than placebo, greater than 1%. When you actually look and you break it down, for a lot of these medicines, everything on that list as “may be a potential risk” is within a few countable numbers of percent. For some of the drugs, everything is within 1% or 2% of the placebo. There is really no difference. Then, when you start to look at your experience with these patients, having put large numbers of people on these medicines, patients want to know, what do I expect? 

Well, I expect your psoriasis to get clear, and any arthritis you might have had that you might not even have known about, that little pain you got used to, maybe goes away. I think in that end, you really have to outline the benefits and not overemphasize the risks because I think that is a lot of what we do—there is that almost protective, scared feeling. You think about the length of the experience that we have had with methotrexate, and you start to question, is that really a good experience we want for our patients, to have to think about liver fibrosis? There are real data about methotrexate reducing the effectiveness of vaccines. We are talking about this known risk. What I think people think of is this unknown risk, but to Dr Boh’s point, it is no longer an unknown risk because it has been out in the wild for a lot of patients. For 10 to 20 years now we have been targeting this mechanism. We have actually refined our targeting over the years. It is better now that it was before. I like to say, as [Mark] Lebwohl, MD, always says, we know what happens in people who do not have any IL-17, all they get is some candida infections, and that is really it. That is the worst thing that could happen; it is not so bad.

Brad Glick, DO, MPH: Neal, let me ask you, when is it appropriate to switch patients from a topical to a biologic, and what are the barriers to switching?

Neal Bhatia, MD: It is funny; as George and Erin were both speaking, I was going back to my program director days, and you all 3 are still active teachers. I wonder how well we are teaching our residents in our first 5 years out about the old drugs. Brad, you mentioned tried and true methotrexate, cyclosporine, and acitretin—are those still tried and true in 2021 for residents coming out? All they hear about are those fossil drugs, if you will. I would be curious to see what the next generation thinks about that. To your question about topicals to biologics, surface area is everything. Surface area and location should be your first 2 drivers. If you see someone with psoriasis on their scalp, it should tell you one thing right there: OK, we’ve got to work from within, not just work from without. You see someone with heavy involvement of their back, in areas that are hard to reach, or like I mentioned, in the nails. Dermatology patients and dermatologists like to treat with topicals. There is no question. 

We always will need something for breakthrough. Biologics will always have a potential for breakthrough, but you still need to think about surface area. If you have someone with 3% surface area, but that 3% is in their scalp, would you not be leaning toward treating them with a biologic in the first place? If you have someone with 6%, but it is on their elbows and knees, and oh yes, their nails as well, would you not be thinking about a biologic in the first place, or at least, your threshold would be very small, to let them get over? I think, from a practical standpoint, many of us would treat with topicals while we are doing paperwork to get biologics approved. I do not think that is a bad thing to think about, and if they start to get better, then we push things back. Or we still think about it, do we use something with a longer dosing strategy as well? There are a lot of different variables to it. I think psoriasis may be the 1 disease where we may bypass the oral concept. There is always a paradigm of topicals to orals to injectables. I think, to the discussion we were having, we may find ourselves marginalizing orals one day, unless we find something really that is safe, and easier. Again, maybe the JAK inhibitors, or the tyrosine kinase 2 inhibitors that are coming up may change that equation a little bit, but I do think we probably could hope for a day where we have to bypass using methotrexate, because I do not think it fits into our paradigm anymore.

Brad Glick, DO, MPH: If you enjoyed the content, please subscribe to our e-newsletters to receive upcoming Peer Exchanges and other great content right in your inbox. Thank you, everyone. Have a great evening.

Transcript edited for clarity.