Video
Novel Therapies Under Investigation for Atopic Dermatitis
Author(s):
Current barriers faced by healthcare professionals who treat atopic dermatitis and anticipation regarding opportunities emerging in the field.
Melodie Young, MSN, RN, ANP-C: Let’s go into emerging treatments. There are so many things about to come into the marketplace. Some of those that we were expecting to have in April or May of this year were pushed back just a little by the FDA, not because of safety issues but because the FDA has been a little busy in the last year. These are about to hit the derm world in a big way. I’d like to talk about the new emerging therapies that we have and perhaps what some of those unmet needs are and additional cons and opportunities for targets that are going to be developed for new topical and systemic oral as well as potential injectable therapies. Keri, you want to start us with that?
Keri Holyoak, PA-C, MPH: I completely agree. It’s an exciting time in the world of atopic dermatitis. There are going to be more choices with creams, pills, and injections. The world is going to be a better place with all these new emerging therapies on the way. One limitation that we have right now is the current guidelines haven’t been updated to include these medications approved for atopic dermatitis. One thing we’ll see down the road is an updating of the current guidelines. Access to medications can also be a limitation, but those are issues we’ll work through. The JAK inhibitors and the monoclonal antibodies will be transformative in dermatology and also in medicine. Early studies show that they’re very effective and acceptable to patients. Although there are some things to work through, like blood work and monitoring, it will give us another potential approach that will be embraced and used. My hope is that it will limit the use of topical steroids.
Melodie Young, MSN, RN, ANP-C: You feel like there is a need because we still have patients who are not as clear as they could be with what we have on the market or who perhaps have failed dupilumab. There are definitely folks in there. There are a multitude of reasons that we want to avoid some of those other systemic agents, methotrexate and cyclosporin, which are not fun to use.
Melodie Young, MSN, RN, ANP-C: Douglas, why don’t you begin to give us an introduction into what we’re going to see and what we’ll be able to discuss more over the next year or so in the dermatology world.
Douglas DiRuggiero, DMSc, PA-C: All the evolution of these treatments is following the research that we’re able to do. This has been a tougher disease to nail down than it was for psoriasis, but now we feel like we have a pretty good handle on the inflammatory pathways taking place. The evolving landscape falls into 2 categories: blocking receptors outside the cells or modifying the receptor intracellularly inside it, which JAK inhibitors are doing vs the monoclonal antibodies. We have monoclonal antibodies, and these are basically the treatments that have a -mab at the end of the word which stands for “monoclonal antibody.”
Our T cells grow up in the thymus and migrate to the lymph nodes. As you have this dendritic cell on our skin that comes across as inflammatory—this exogenous particle, this microme, or whatever it is that shouldn’t be there—it attaches it to itself and runs down to the lymph node. Then it taps the shoulder of this naïve T cell and shows them this thing. That becomes an antigen-presenting cell at the time. If it presents to that naïve T-cell IL-4 at the same time, then it helps differentiate into a Th2 cell. To present IL-23, it’s going to go toward Th17 in the psoriatic pathway, where it can present IL-12 and the Th1 cell. You’ve got this IL-4 that makes that T cell differentiate into a Th2 cell.
All our therapies that are coming into this is realizing the cytokines that are impacted by that pathway or the other pathways. In atopic dermatitis, we know the key cytokines were IL-4, IL-5, IL-13, IL-31, and IL=33. Now we can target these things. We don’t have to use the B-52 bombers or the old treatments to try to wipe out the whole town. You send a sniper, and they hit these particular targets. “These are IL-13 inhibitors, lebrikizumab, tralokinumab; IL-31 inhibitors, nemolizumab; and IL-33. You can see that they’re targeting these particular areas, some that have a higher tendency to control, some that are controlling the hyperkeratotic side of this disease. Some are spongiosis more specifically, but they all address the disease state itself. If you can’t block it outside the cell, we now have isolated these JAK inhibitors, which are just on the inside of the receptor and are modifying what happens inside the cell. When JAKs were first discovered in 1989, they thought it was another kinase, JAK, because we were beginning to isolate different kinases, which are just enzymes. By definition, a kinase is an enzyme that will put a phosphorylate a PO4 molecule off the ATP onto something else, another substrate. All these JAK inhibitors that are inside the cell modify phosphorylate something called STAT. By doing that, it helps turn off the gene expression in the cell that’s upregulating this inflammatory pathway.
The landscape is evolving as our science gets better and as our knowledge increases. It’s basically saying that we don’t need to put more cream on; we need to give it more thought. More thought leads to more research, and more research leads to targeted therapies and extracellular therapies, which come in the form of monoclonal antibodies. Now we’re seeing small molecule intercellular therapies, which all end with -nib, meaning “inhibit,” like to inhibit kinase; it’s anything that’s a kinase inhibitor or has the -nib at the end. If it’s a tyrosine kinase inhibitor, which all the JAKs are, then it’s -tinb at the end of the name. That’s how we see these names evolve. You can look at a therapy, and if you see -tinb at the end, you know it’s a tyrosine kinase inhibitor, a small molecule intercellular, that’s mechanism of action. There are lots of names for these: tofacitinib, baricitinib, and upadacitinib are all blockers, intercellularly. That’s the class of 4 types of these things: JAK1, JAK2, JAK3, and the tyrosine kinase 2.
Melodie Young, MSN, RN, ANP-C: Thank you for watching this HCPLive® Peer Exchange. If you enjoyed the content, please subscribe to our e-newsletters to receive upcoming Peer Exchange segments and other great content right in your in-box.
Transcript Edited for Clarity
