Advances in the Management of Plaque Psoriasis - Episode 6
Mark Lebwohl, MD: I see the treatment landscape evolving a lot. In the last few years, we’ve seen the benefit of the IL-17 [interleukin-17] and IL-23 blockade. Here are drugs that don’t have black box warnings for malignancy or infection, so they’re substantially safer than what we used to use. They are very effective, the PASI [Psoriasis Area and Severity Index] 75 levels are approaching 90%, even respectable PASI 100 levels are occurring with these drugs. I think that more patients will be shifted to IL-17 and IL-23 blockers. There’s a little bit of hazard in that biosimilars for the TNF [tumor necrosis factor] blockers are just coming out. Whether insurers will push patients to those less expensive drugs remains to be seen, but certainly they carry more risks with them. I see also that on the horizon, there are many more IL-17 and IL-23 blockers in development, and I think that’s going to be the future of the treatment of psoriasis. I think we are going to see much more in the way of the IL-17 and IL-23 blockade among the patients that we treat.
There are several JAK [Janus kinase] inhibitors in development, actually more for atopic dermatitis than for psoriasis because there’s a bigger need there. We don’t have as many biologic therapies for atopic dermatitis, although that also is changing. We’ll be seeing more biologics for atopic dermatitis. But the JAK inhibitors have already been tested for psoriasis. Tofacitinib is approved for psoriatic arthritis. It was proposed to the FDA for psoriasis, and they have very well done studies that showed that it was at least comparable to etanercept. But the FDA chose not to approve it for psoriasis probably because it is somewhat immunosuppressive. There was an increase in herpes zoster cases. Had that come in front of the FDA 20 years ago, tofacitinib is certainly safer than cyclosporine and methotrexate. I think it might have been approved 20 years ago, but now because we have all of these biologic therapies, the FDA didn’t approve it for psoriasis.
The other JAK inhibitors that are coming out also have some adverse effects. They’ve been associated with some thromboembolic events. They’ve been associated with some immunosuppression, although certainly the adverse effect profiles of all of those drugs are superior to the pills we currently have, methotrexate and cyclosporine primarily. That’s both for atopic dermatitis and for psoriasis. The drugs have some major safety advantages, but they also have efficacy advantages over the safer oral therapies we have for psoriasis—apremilast and acitretin. The JAK inhibitors by and large are more effective than those.
The 1 that has been tested and had very good phase 2 results with very little downside was a TYK2 [tyrosine kinase 2] inhibitor, a tyrosine kinase inhibitor. I do think that that will get approval. The question will rest on what happens in their phase 3 trials. Will they have blood monitoring? Will they have safety warnings that are comparable to the Janus kinase inhibitors that are available, or will it get a better adverse effect profile and better package insert as a result? That remains to be seen.
Transcript edited for clarity.