Mark Lebwohl, MD: We’ve made this segue now to biologics from oral medicines. Why don’t we start with the oldest ones? How do they work? How are they given? When do you use them? We’ll start with the TNF [tumor necrosis factor] blockers. George?
George Han, MD, PhD: Our TNF blockers out there are etanercept, adalimumab, and infliximab. And there’s slightly newer one, certolizumab pegol. What’s interesting is this class actually has probably the most variety out of all the classes of biologics that we have with regard to the different kinds of antibody designs they have but also the dosing regimens. I think if you look at a medication like infliximab, that’s an infused medicine, it’s something that has a pretty rapid efficacy. But unfortunately, a lot of antibodies can form to it, so you start to lose efficacy. So I find myself not using very much of that nowadays. If you look at etanercept, it has a very long track record of success, but the efficacy is just really not up to our modern standards of where we can get people to. You can get a person to about 70%, on average, PASI [Psoriasis Area and Severity Index] improvement with etanercept. That might have seemed great 15 years ago, but nowadays it isn’t so much.
Brad Glick, DO, MPH: And the frequency of injections, George, are just a lot, particularly what we have right now with drugs that can be dosed every 3 months. It’s twice weekly for 3 months and then a step down. And I would agree also that not only is the efficacy at the end of 3 months compared to what we have now certainly less, but then when patients step down to once weekly dosing, they lose additional efficacy. That was my experience, but like any other drug I’ve hit many a home run with etanercept in my time. But I have to tell you, I have no one left on etanercept right now. It has really been replaced. I’m sad to say, but the drugs that we have now are just so much more highly effective. And as we climb up that ladder of efficacy, our safety profiles have been far, far superior.
Scott Gottlieb, MD: Right, and that’s where I wanted to chime in because we mentioned efficacy, we mentioned frequency of dosage. And I think we also have to think about TNF inhibitors and their safety profile, which are clearly not as good as some of the newer more targeted agents. I think you brought that up before, Mark. I think we’re in agreement that it may be a little bit old school there.
George Han, MD, PhD: I think speaking to those safety issues, tuberculosis, hepatitis B reactivation, this is where this all came from. If you imagine a blank slate where we had all our biologics and we started with maybe the IL-23 [interleukin-23] class, we wouldn’t even be thinking about this, right? So, if you look back at the TNFs, those are concerns, nonmelanoma skin cancers. We’re starting to see a slight signal of squamous cell carcinoma, a little more than basal cell. Those are all things to think about with the TNF class. We go to adalimumab. Certolizumab pegol, it’s an interesting one. It’s unique in that it’s a fragment and it’s pegylated. It doesn’t cross the placental barrier. There are some other attractive assets. But all of these are in general every 2-week injections at the lengthiest. And really that’s something where if you ask most patients—if you say, “I have a medication that works better that’s injected less frequently”—by far most of them will probably ask you, “When can I sign up for it?”
Scott Gottlieb, MD: George, the pivotal clinical trials of almost all the newer agents, maybe not the newest agents, but most of them, have used a TNF inhibitor as the comparator drug. And so we have nice head-to-head trials showing the TNF agents and the newer agents, and the newer agents uniformly have beaten out the older agents in terms of their efficacy.
Brad Glick, DO, MPH: But I have to chime in that TNFs are still here to stay, of course, because there are certain contraindications because of comorbid conditions that our patients have. And certainly, TNFs by far and away in the biologic area are quite effective, such as with inflammatory bowel disease. And I hate to be the one always on the kick of inflammatory bowel disease, but certainly the nice thing about TNF inhibitors is we can tell our patients as well and our colleagues that they cover the joints, they cover the skin, and they cover the gut. And I think that that’s a really important component of that particular class of agents, which still makes them unique despite the dosing frequencies.
Scott Gottlieb, MD: As long as you brought up psoriatic arthritis [PsA], I think it’s interesting that we’ve all noted that the newer agents have better efficacy in terms of plaque psoriasis. But in psoriatic arthritis, I don’t see that the bar’s been raised. And I think some of the TNF inhibitors do fairly similarly to some of the newer agents in terms of psoriatic arthritis. And I wonder why. At some point I’d like to see an agent that also raises the bar in terms of psoriatic arthritis. What do you think, Mark, about that?
George Han, MD, PhD: That might be coming from what we’re seeing out of some publications with an IL-17. But going back to what you said about PsA, we’re still supposed to, by guidelines, use that first- and second-line for psoriatic arthritis, right? And I think it’s because of that length of data that we have. We know that psoriatic arthritis is a progressive destructive joint disease, and so that confidence that you have over a longer period of data and following patients has really driven most of that. We have that confidence that it really helps prevent progression of disease.
Scott Gottlieb, MD: And is that what you do with your patients typically?
George Han, MD, PhD: I find that optimizing for psoriatic arthritis is a rare thing I do because even for patients who do have it, it’s not that the other agents don’t cover it. It’s that if they really have severe enough PsA that it still breaks through with a different class of agent or something like that, then I might consider it as a strong driver of a treatment choice. Because right now, we’re talking about an age where it’s not just what is the best drug, it’s what is the best drug for this patient.
Brad Glick, DO, MPH: Absolutely.
George Han, MD, PhD: What are the drivers here that I’m optimizing for in my treatment selection?
Brad Glick, DO, MPH: Have we gotten a little too caught up on radiographic progression? I think that’s particularly important. With adalimumab, that was a really important factor we discussed with our patients who we suspect may have psoriatic arthritis. And certainly, we now have that with IL-17 blockers, but then it comes into question with IL-12/23, and maybe even with interleukin-23. Because progression of psoriatic arthritis, as Dr Lebwohl mentioned before, is a highly debilitating disease. I think TNFs are here to stay, but nevertheless, when we have these powerful agents with these dosing frequencies of 4 or 6 times a year, it’s quite favorable for our patients when they’re making those selections.
Mark Lebwohl, MD: Yes. I will say I have hardly ever, if ever, in the last couple of years prescribed a TNF blocker as my first choice for psoriasis. I actually routinely use them for sarcoid granuloma, for which they’re all off-label. And now of course on-label is hidradenitis, although some data are coming out about some of the newer agents as well. But there are many uses for TNF blockers, and I prescribe them almost every day that I practice, but they’re hardly ever my first choice for psoriasis.
I do have patients though who started on the oldest of the TNF blockers, which is etanercept, and are still clear years and years later. I’m not taking those patients off. I will also point out we have great data on the reduction in heart attacks in patients on TNF blockers. Those data come from registries where they almost all show a 50% reduction in heart attacks. Now, I bet that we’re going to see those same data for the new drugs too, but they haven’t been out long enough to establish those data. And so far, the TNF blockers still have an important place, an important role in that as well.
Transcript edited for clarity.