The Changing Treatment Landscape of Plaque Psoriasis - Episode 5
Dermatology experts comment on the safety profiles of biologic therapies used to treat plaque psoriasis, highlight specific contraindications to be mindful of when prescribing these drugs, and provide suggestions to help mitigate the risk of adverse events.
Andrew F. Alexis, MD, MPH: Let's shift over to safety. Just as important as efficacy is safety. Dr Boh, what are the adverse effects? What are some of the adverse effects that we should be mindful of when thinking about the various classes that Dr Blauvelt covered, specifically TNF inhibitors, the IL-12/23 inhibitor class, and the IL-17 inhibitors? What are the key adverse events we should know about?
Erin E. Boh, MD, PhD, FAAD: Well, I think there are not as many as we had with our systemic therapies. Just to set everything in perspective, as a group, the biologics are very safe. They have a good safety profile. If we look at the first generation of biologics, which I like to call the TNFs, because those are the ones that we really have a lot of data on, there are some adverse effects, and they're not going to be for everyone. In general, the adverse effects are few, but what we have to think about is patient selection. If you take the TNFs, people who have morbid obesity, that may be an issue with the TNFs, because most of them are not weight based, except the infliximab, and most dermatologists don't use infliximab. I love it. It's great for patients who are obese. The other thing that can happen with the TNFs is some people will have a paradoxical weight gain. In general, if you're on the TNFs, you have to be careful if you have severe congestive heart failure [CHF]. You'd have to be careful in terms of the risk, very low, of inducing or unmasking a multiple sclerosis [MS]. People with first degree relatives with MS, I steer away from the TNFs. You want to remember that the TNFs as a group can degranulate.
As a consequence, you can reactivate old TB [tuberculosis]. You can also reactivate hepatitis B. They're going to require screening, and a little bit more blood work with them. The TNFs, as a group, can increase or induce elevations in your liver tests. You have to be a little bit careful about that. Those are not very common, but they are ones that we want to watch for. There is a very slight increased risk of malignancy, especially maybe squamous cell carcinoma, with the TNFs. But again, not too bad, but theseare things we need to monitor more than the third generation of biologics.
If you look at ustekinumab or the IL-12/23s, they do have a very good safety profile. The adverse effects that I can come up with for ustekinumab are a couple. One, some people can't go the whole time. They can't control going 12 weeks. The majority can, but some will break through. It's not as good for joints as our TNFs, which are first line for prominent psoriatic arthritis. There are some people for whom it just doesn't respond. Ustekinumab's safety profile is very good. There was initially some ruckus about maybe inducing a little bit higher incidence of MACE [major adverse cardiovascular events], especially with these drugs. That hasn't played out in the long run.
If you take the second or third generation of biologics, the IL-17s, they're even safer and have fewer adverse events as opposed to the TNFs. As you go closer to the pathogenic bullet in psoriasis, I think many of the adverse effects get less. With the IL-17s, what do we need to watch for? We certainly have a slight increased risk of yeast infections, candida infections. The big thing with the IL-17s, of course, is going to be inflammatory bowel disease. You want to take a careful history because you could unmask it, or you could induce it even. That's a very low risk.
Simple questions and screening would help mitigate that, but you do have to be careful because it can unmask or induce an inflammatory bowel-like process. That's something that you do want to be careful about. There is a black box warning, of course, on one of the drugs, brodalumab, in terms of increased risk of depression. In general, I don't worry about that too much. Patients with psoriasis generally are more depressed than other people anyway. I don't think that brodalumab is going to make it that much worse. But again, all patients need to be screened for depression who have psoriasis.
We do follow our patients on brodalumab a little bit closer to make sure that they don't have that adverse effect, but other than that, as a group, they're very safe. We just look at what we have to monitor, and that tells us the potential adverse events that we would see with the drugs.
Andrew F. Alexis, MD, MPH: All right. Thank you. Now, Dr Armstrong, just briefly, I know Dr Boh has pretty much mentioned all the major adverse events we need to know, but any specific contraindications, no-fly zones, for each of the classes that we've discussed so far? April?
April W. Armstrong, MD, MPH: Yes. First of all, for all of the classes, they have in their label, hypersensitivity as a contraindication. That's probably as expected. One consideration that's common to all of the different classes are things like injection site reactions, nasal pharyngitis, and upper respiratory tract infections, which can be seen with the biologics in some with an increased risk compared to the placebo. With TNF inhibitors, we want to make sure that we avoid those in patients with demyelinating diseases such as MS, patients with advanced CHF.
I thought Dr Boh did a wonderful job summarizing some of the key safety considerations regarding the IL-17 inhibitors. There are low rates of oral candidiasis that most dermatologists are comfortable treating, and typically it's not a reason for discontinuation. In the IL-23 class, overall as a class, there are not any discernible safety signals other than the contraindication that applies to all biologics of hypersensitivity.