Jerry Bagel, MD, MS

I think we’re in a pretty good place. We have drugs that are FDA approved, [taken] 4 times a year, and 65% of people are clear, 80% of them are 90% better, and they don’t have many adverse events to talk about. I think we need to learn how to compound other topicals with them [approved drugs] to get rid of the rest of the psoriasis. I know the National Psoriasis Foundation, where I’m on the board of directors, is involved with $4 million of funding research a year, where we’re trying to look at what is really causing psoriasis to begin with. I still think all of that is about 10 years away. But when people asked me about this question 15 years ago, I never thought I could think about a cure back then. I can start thinking about that now. I think there might be a little lag in the development of more drugs also because biosimilars are going to come into play. I think we’re going to be forced to use some biosimilars along the way, and that will interfere in the economics of pharma [the pharmaceutical industry]. I think we’re in a pretty good place right now for moderate to severe psoriasis.

I also teach in Italy, and they have centers of excellence, like 100 of them, and if a patient gets into one of them and needs a biologic, they get it. So I think access, patients’ access, somehow needs to be improved so that more people can get it. Most people don’t realize that if they come to your office, they’re not going to have to pay thousands and thousands of dollars for their drugs. There’s going to be some sort of assistance program for most people who need it. I wish they knew that because then they would come in and get treatment instead of suffering.

If you talk to any of the major representatives, they’re going to know, there’s an ambassador program from AbbVie Inc [Chicago, Illinois], there’s another program from Janssen Pharmaceuticals, [Beerse, Belgium], there’s a different program for Eli Lilly & Co [Indianapolis, Indiana]. They all have programs that can help their patients. I think that would be something if people knew about, they would [be more willing] to make an appointment and see people who are willing to treat them.

With psoriatic arthritis, it is one thing to help someone who has psoriasis, you want to make them look better and feel better. But if you have joint discomfort, you really want to get on top of that because if you don’t, it’s going to continue, and you’re going to be disabled. So it would be really good if you have any joint discomfort with psoriasis, to get people to jump on that because it would be a shame. There are decent drugs right now. There could be better [drugs] for psoriatic arthritis, but there are decent drugs that are also safe, that could help save your joints from destruction.

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Dr Jerry Bagel looks to the future of moderate-to-severe plaque psoriasis management.

The Future of Plaque Psoriasis Management

Bimekizumab is awesome. We did clinical trials with that as well. Its PASI 90 [90% reduction in the Psoriasis Area and Severity Index] is close to 90%. There’s nothing like it. It’s administered 320 mg, either every 4 weeks or every 8 weeks, it hasn’t been decided yet. But an 8-week dosage works just about as well as every 4 weeks. You have a drug that’s an IL [interleukin]-17A/F monoclonal antibody that works probably as good, maybe better, than an IL-23. It didn’t show any inflammatory bowel disease or ulcerative colitis in its clinical trials like with the other IL-17s, but I bet the FDA still lumps it with inflammatory bowel disease. One thing that was a little troublesome was 20% of all patients developed candidiasis, yeast infections: mouth, vaginal, and skin. Almost none of them discontinued bime [bimekizumab] because of it, but it needs to be looked at, treated, and we’ll see how we deal with it. Dermatologists, we deal with yeast, so we know how to handle that, but the thing is we had 1 patient who had it with each dose. We had to treat them with Diflucan [fluconazole] right before, and that covered it. That was helpful. I think of it very highly, and it has really good PsA [psoriatic arthritis] data, really good. So you have another drug coming out that is going to be very helpful. Again though, there’s going to be a certain percentage of people who don’t clear, and they’ll still have some residual psoriasis.

Assuming that the candidiasis is just a mild issue, which we didn’t see many cases, I think that bimekizumab would be my No. 1 IL-17. I’m not afraid to say it. And I think Taltz [ixekizumab] is a really good drug, and I think brodalumab, even though it has a black-box warning for suicide, is a good drug. But I think bimekizumab probably has better efficacy, and probably would be my No. 1 IL-17. And I would now start discussing deucravacitinib with my patients as an oral option, which before I wouldn’t. So there would be an oral option, an IL-17, and probably an IL-23 that I would choose from. That would be my selective group right there.

Jerry Bagel, MD, MS, explains clinical trial data on the investigational anti-IL17A/F monoclonal antibody bimekizumab.

Emerging Plaque Psoriasis Agents: Bimekizumab

Deucravacitinib is a new brilliantly designed molecule that binds the allosteric pseudokinase portion, pseudodomain of the JAK [Janus kinase] molecule. It doesn’t really bind the JAK where it phosphorylates STAT [signal transducer and activator of transcription], it binds it at another part of the molecule; it twists it, so it doesn’t allow it to phosphorylate all the JAKs, and that’s the point. It’s not inhibiting all the JAKs; it’s only inhibiting some of the JAKs. Therefore, it’s not resulting in all the adverse events that you would see if you were inhibiting JAK1, JAK2, JAK3, etc. It’s only inhibiting tyrosine kinase. It’s a different mechanism of action completely. So, by binding and inhibiting that, STATs don’t get phosphorylated, they don’t go down to the nucleus and induce transcription of these inflammatory molecules, specifically IL [interleukin]-12, IL-23, and interferon. That’s what it’s inhibiting. By not inhibiting all the JAKs, you don’t see thrombosis, malignancy, or high triglycerides in its adverse event profile, so it’s slightly different. 

As far as how it works, it’s 6 mg PO [by mouth] QD [every day]. And at week 16, head to head with placebo and also against apremilast, it had a PASI 75 [75% reduction in the Psoriasis Area and Severity Index] of about 65%. It also has some good PsA [psoriatic arthritis] efficacy. When you go head to head with apremilast, which has a PASI 75 of about 30%, it’s about twice as good, which to me is a game-changer. This is a game-changer. I didn’t prescribe apremilast much because at 30% efficacy I didn’t feel that I was offering my patients a high enough benefit to really take a chance on the nausea, bellyaches, diarrhea, headaches, and possible depression. I never used it a lot, but it’s a $13 billion drug, so someone is using it.

But this now has efficacy that’s twice as good. I will definitely offer this oral medication. It will be interesting to see how when you pitch it to your patients directly, like, “Hey, I’ve got a pill that works, you’re going to get 75% better two-thirds of the time, or I’ve got a shot that I can give you every 12 weeks, and you’re going to get 75% better 95% of the time.” It will be interesting to see what people choose.

I think a lot of people do want pills, just by the fact that apremilast is a $13 billion drug. When [a patient] enters into a psoriasis center, you really want to give everybody the best options, and that’s why I didn’t always offer apremilast. It’s usually those people who would ask for it.

I think ultimately people prefer pills to shots. In the end, as long as there’s efficacy and the adverse event profile is good, I think many people will prefer a pill to start with to see how it works, and we give it 16 weeks and see if they’re happy with their overall response. That’s the major one that’s different. The question will be though, as I said, if it’s a JAK, then it’s going to have to be monitored. Apremilast didn’t have to be monitored, so we’ll have to see where it turns out.

Hopefully, it will get a favorable PI [prescribing information approval] from the FDA, and it’s not necessarily in the JAK family, but we’ll see.

Basically, it’s head to head with placebo, 6 mg PO QD for 16 weeks. The average person had an affected body surface area of about 20%. They were about 45 years old. They were mostly biologically naїve, and there were about 1000 people overall in the study, which is quite a few. At week 16, that was a primary end point of PASI 75, but they also showed that there was a significant improvement in itch, DLQI [Dermatology Life Quality Index] was significantly improved down to almost nothing. The adverse event profile looked really clean. And at week 16 they all converted over, including those on placebo, to continue deucravacitinib through week 52, and the efficacy improved somewhat to I think about 65%, 70% of PASI 75 by week 52.

Assuming that there’s not much monitoring, then I think it will go over really well. But let’s look historically. Even apremilast took a few years before the insurance companies were really letting us write [a prescription for] it. They were actually having patients fail Humira [adalimumab] or Enbrel [etanercept] before going on apremilast. That could transpire here as well. It’s going to depend a lot on how BMS [Bristol Myers Squibb] and the insurance companies work their magic to allow for access. That’s going to have to be an easy one because people aren’t going to fight too hard because they don’t have the time.

The TYK2 [Tyrosine-protein kinase 2], even though it may have a JAK PI [phosphatidylinositol], is not a JAK inhibitor, and the adverse event profile does not show any of the JAK troubles like thrombosis, MACE [major adverse cardiac event], malignancy, and triglycerides. I think they need to be more aware of the safety of this drug compared to other JAKs that are going to be out there.

An overview of the novel selective tyrosine kinase 2 (TYK2) inhibitor deucravacitinib for the management of plaque psoriasis.

Emerging Plaque Psoriasis Agents: Deucravacitinib

How do we go back to the point where [we find] what is being activated, either a dendrite or a keratinocyte that’s activating the whole system? How do we prevent that from happening? I think [another unmet need is] predicting which people respond best to which drug in the beginning. We’re starting to do that now with pharmacogenetics, which would be very helpful. It would be nice to know if a drug worked 70% of the time, well, how can we figure out who that 70% is? Then the other 30% would use something else. I think other unmet needs, even though I say the IL-23s [interleukin-23 inhibitors] are safe, there’s still an increased frequency of nasopharyngitis or upper respiratory tract infections. It would be nice if we could eliminate adverse events completely. It would be nice if we can get people who could be clear, but also I think access, making access easier because not everybody can afford to have their own biologic coordinator. Some offices can’t. They don’t do as much volume, but making access easier for patients would also help.

I think the PASI 90 [90% improvement in the Psoriasis Area and Severity Index] and PASI 100 is what we’re looking at now for most biologics. I think we have somewhat reached a ceiling, although there’s still some room for improvement because even the best biologics give you a PASI 100 of maybe 60%, 62%. So there are still a third of all patients who are not clear.

Dr Jerry Bagel describes the unmet needs of plaque psoriasis management.

Jerry Bagel, MD, MS

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