John Tesser, MD: Nehad, let’s get a bit more into the weeds now with some of the pharmacological approaches that we take to our patients. There are more guidelines around than there are medicines it seems but I can mention just a few. There are the GRAPPA [Group for Research and Assessment of Psoriasis and Psoriasis-Arthritis] guidelines; there are the ACR, that’s the American College of Rheumatology, in conjunction with the National Psoriasis Foundation guidelines that came out in 2019; and then the European EULAR [European League Against Rheumatism] guidelines came out last year. So we had a lot of guidelines. They all seem to have something similar in common, which gets back to something you brought up originally and that was the domains. Maybe you want to get into these a little bit and get us structured on them.

Nehad Soloman, MD: When we think about domains, we think about skin, we think about peripheral arthritis, we think about dactylitis or, as Jen mentioned, the sausage-like swelling of digits; fingers and toes; enthesitis, that’s the inflammation of the tendon and ligament insertions at bone; and then spinal involvement. Those are the several domains that everybody thinks about when starting to choose treatments. When we start looking at the guidelines, clearly if something is mainly skin and minimal joint or ligament-tendon involvement, then the focus is going to be oh, perhaps you can use something a bit milder, maybe focus more on topical agents if it’s limited.

But then you look at the severity of involvement as well. If you have body surface area, we calculate by quickly looking at the patient’s palm or the size of their palm and assessing how involved. If you took their palm and put it over the various areas of psoriasis, how many palms would that be, and every palm would be equal to 1%. And so, when you start exceeding 3%, 4%, 5%, even 10% body surface area or 10 palms, if you will, then you know you’re on the severe end and you’re going to want to be a bit more aggressive with systemic agents. Then, when you start thinking about systemic agents, which 1 you are going to pick, depends on the number of domains involved. So if you have lots of skin and peripheral arthritis, you may want to use a systemic agent, maybe a biologic upfront. If you’ve got mild skin and really focused on some spinal area, then you may not want to use a small molecule conventional DMARD [disease-modifying anti-rheumatic drugs] and really focus your efforts on something that has a bit more punch in that respect, perhaps a TNF [tumor necrosis factor] agent or an IL [interleukin]-17.

But that’s where again the comorbid conditions may come in and start to sway your decision because if they have inflammatory bowel disease, then you sway away from the 17s, and then perhaps you think about IL-23s. All of those things, and maybe you want to use a combination therapy depending on, again, the extent of disease, the severity, and the number of domains [involved]. If they have iritis or uveitis, you may again gear more towards the TNF agents that have a multitude of different indications, and so you may be capturing they have IVD [in vitro diagnostics], and they have uveitis, and they have psoriasis, and they have psoriatic arthritis. Well, the TNFs seem to make the most sense. But, if they have a family history, a first-degree relative with MS [multiple sclerosis], or they have active CHF [congestive heart failure], you may again alter your method of treatment in that case. So when you look at these guidelines, they sort of start to pick apart if this then that, if this then that. But it’s not 1 sort of standardized algorithm which gives us the liberty to be clinicians and that’s 1 of the beauties of rheumatology is that we get to practice a bit differently and patient centric.

John Tesser, MD: Jen, it’s interesting, some of the nuanced differences, well maybe they’re not so nuanced, between the American and the European guidelines. The American guidelines speak to using conventional DMARDs for a light amount of disease, but the first way to go if there’s more than that would be a TNF over an IL-17 and then an IL-17 over an IL-23. The European guidelines say to jump right in with a TNF even before conventional therapy, conventional DMARDs, which of course include methotrexate, leflunomide, and sulfasalazine. I think that it is interesting to think about those differences. I’m going to ask you about that in a second.

I’m just going to make a comment that seems to be pointed out by both of the guidelines which are to identify functionality as being intrinsically important in determining whether to use advanced therapies against basic conventional therapies. And the interesting point is made, particularly in the European guidelines, that if someone has only 1 or a couple of joints involved or entheses involved, then you might use lighter treatment. But, on the other hand, if a patient has 1 or 2 joints that are significantly affecting a person’s functionality, let’s say it’s particularly in a lower extremity joint or perhaps enough involvement of a wrist or an elbow and it’s affecting the functionality of a limb, that in and of itself should be considered a more severe disease and would then steer treatment in that way.

Similarly to what Nehad said, if there’s a lot more skin involvement, and I particularly like the way you pointed out how to assess someone’s amount of skin involvement by percent of body surface area, then you may be looking at moving more quickly to the advanced biologic therapies or the targeted small molecules rather than just conventional therapies. But there seems to be this understanding that conventional therapies maybe have less punch than some of these others.

This transcript has been edited for clarity.