A historical overview regarding the advances in biologic therapies to treat plaque psoriasis and real-world experience using newer classes of biologics in clinical practice.
Andrew F. Alexis, MD, MPH: We’re going to go back to Dr Blauvelt. Now that we’ve got this overview of the various biologics available and the evolving paradigms as far as initiation of therapy, could you kindly discuss your experience with what we’ll call the first wave of biologics starting with TNF [tumor necrosis factor] inhibitors, subsequently the IL-12/23 inhibitor class, and IL-17 antagonists?
Andrew Blauvelt, MD, MBA: Sure, Andrew. Thank you for asking me that question. I feel like I’ve ridden the wave of all these over time. I was involved in the approval of efalizumab, which was the second biologic drug for psoriasis, in 2003. The first TNF came out in the spring of 2004 for psoriasis, and that’s etanercept. As soon as it was approved, I started using it. We all thought it was this incredible drug. I was chief of the VA at that time, and I had to get this new drug on the formulary at the VA. That was my big thing.
We used it right away, and we thought it was wonderful. Compared with some of those older things that April talked about—topicals, phototherapy, methotrexate, acitretin—most of us thought etanercept was a big move forward. Then we had infliximab in 2006 and adalimumab in 2008. I’d say both drugs had higher efficacy, in my experience. I moved to those drugs, I would say quickly, from infliximab to adalimumab, because it was subcutaneous, whereas infliximab was IV [intravenous]. In my experience, I was using them a lot when they first came out, with good success, thinking they were great.
The next drug approved was in 2009, and that was ustekinumab, an IL-12/23 blocker. I thought that was much better. Look at the efficacy at that time, and the efficacy looked better than all the TNFs except perhaps infliximab. It seemed safer to me, and that was my experience as I started to use ustekinumab. For many years, that was my go-to drug because we didn’t have the next biologic approved until 2015. For those 6 years, I’d been evolving and using the latest and greatest. I’d been quickly adapting and quickly accepting them as time went on.
With ustekinumab, everyone seemed to love the infrequent dosing, the lack of major adverse effects that we would see in some of them with the TNF class, but we didn’t always. I guess the problem, in my experience, with ustekinumab over that time period was that not everybody could go 12 weeks. A lot of folks ended up breaking through around the 8-week, 10-week time point. Sometimes I could get them to every-8-week dosing and sometimes I couldn’t. There was some deficit there in that armamentarium or with that drug. The other thing developed over that time is it seemed to be better for skin efficacy compared with TNFs but not as good for psoriatic arthritis. As April mentioned, that has always been in my mind—for patients who have both conditions—influencing my choice.
There was still some need there, some hope for something better that would have the skin efficacy, but maybe some better joint efficacy, but a lot of the infrequent dosing. Then along came the IL-17 blockers. As April mentioned, that’s secukinumab, ixekizumab, and brodalumab. As a general rule of thumb, the efficacy was higher in that class of drugs compared with ustekinumab and the TNF blocker class. They were receiving even greater levels of skin clearance, both in the clinical trials and in the clinical practice. We saw them working better, in my practice and in my trials, on joint disease than ustekinumab.
It filled some of the niches that we were looking for in ustekinumab. But on the other hand, the dosing was more frequent. They’re either every 2 weeks for brodalumab or every 4 weeks with ixekizumab and secukinumab. To describe my experiences, I’ve been riding the wave and really loving the evolution. Going from class to class and trying, in my mind, to pick the best 1 for my patients. I hate step therapy.
I know we haven’t talked about that yet, but a lot of times that has also been my experience, battling insurance companies—you have to use this, this, this. I agree with April. Over the last several years, it’s been much better not having to go through what Craig Leonardi calls the ladder of shame, where we go through all the older, less effective, and less safe drugs before we get to the good stuff. I really don’t like doing that. Whenever an insurance company will allow me to, I avoid that step therapy and just go with what I think are the best drugs for my patient.
Andrew F. Alexis, MD, MPH: Great. Thank you for taking us along that winding road of evolving therapies and discussing some of the pros and cons.