VIDEO: Exploring the broad range of psoriatic arthritis treatments

Editor’s note: This is an automatically generated transcript, which has been slightly edited for clarity. Please notify editor@healio.com if there are concerns regarding accuracy of the transcription.

Fortunately, we now have a pretty broad range of treatment options. I would direct anybody listening really to the GRAPPA guidelines, which I find are the most helpful guidelines available in thinking through management of psoriatic arthritis. Before getting to the specific therapies, I think it's really important to emphasize that psoriatic arthritis is a disease that really benefits from consideration of domains that you're addressing and on shared decision-making with the patient to determine what domains are bothering them. I can't tell you how many times I've had a patient come in who has psoriatic arthritis and after a long conversation will come to realize that the thing he really cares the most about is his fingernails and it would not be what I consider.

But you know, the example I use is a patient I have that's a ticket teller and because he's passing things under a window to people all the time, he's very sensitive about the appearance of his nails and we might not have picked a treatment that was most reasonable for him without a conversation with him about what domains are really of most interest to him. And so I'll emphasize you really want to talk to the patients about domains of skin disease, nail disease, axial involvement, peripheral arthritis, enthesitis, dactylitis, and really make sure that when you're coming up with a plan for the patient on what option to use, that it matches and addresses the domains of importance.

So that said, you know, I think we have a broad range of treatments to choose from. We have everything ranging from the conventional synthetic DMARDs or oral small molecule drugs, including methotrexate and sometimes thalidomide, although it's not really studied in psoriatic arthritis. These are kind of used often in patients with peripheral joint disease in isolation and relatively modest skin involvement. As far as other oral small molecule drugs, we also have apremilast (Otezla, Amgen), PDE inhibitor, often a medication we'll use in patients with primarily peripheral disease, maybe some enthesitis or dactylitis, some modest to moderate psoriasis. It's a nice tool in the arsenal and particularly is very well-tolerated, has a relatively benign side effect profile.

From there, we're looking at primarily biologic drugs and JAK inhibitors, and we now have several classes of drugs that have been shown to be effective in psoriatic arthritis. The first, broadly speaking, are TNF inhibitors. TNF inhibitors are extremely effective for axial disease. They're effective for peripheral arthritis, enthesitis, dactylitis, and are reasonably good for psoriasis. They are not my top choice for patients with severe psoriasis because we just have some drugs that are going to be better at addressing that domain, but good drugs all around and often first-line for patients with psoriatic arthritis.

[The] second domain we look at are IL-17 inhibitors, so there are three of these now on the market, although one is not yet approved for psoriatic arthritis, although I expect it will be. The first is secukinumab (Cosentyx, Novartis), second ixekizumab (Taltz, Lilly), and then bimekizumab (Bimzelx, UCB). Bimekizumab is currently FDA-approved for psoriasis, but has very good data thus far for axial spondyloarthritis and for psoriatic arthritis. And so we anticipate that that will likely get approval at some point in the near-ish future. IL-17 inhibitors have basically the same efficacy as other TNF inhibitors for joint involvement in psoriatic arthritis and for axial involvement, but really have a leg up in treatment of psoriasis, and so are excellent choices for patients with quite severe psoriasis, especially when that's the main domain of concern and also have more severe psoriatic arthritis or axial involvement.

IL-17 inhibitors, you do need to be aware about the risk for development of new onset of inflammatory bowel disease. About one in 100 patients in trials will develop a new onset of inflammatory bowel disease while on treatment with an IL-17 inhibitor. In real world, I don't see this often, but it is something that we always warn patients about and we notify them that if a patient developed new onset of diarrhea, abdominal pain, blood in the stool, we need to know about it. And these are oftentimes we'll have these patients evaluated by GI. As a result, in somebody who has a history of inflammatory bowel disease or has a, you know, a suggestive history that you're concerned about, comorbid inflammatory bowel disease, these are often drugs that we try to avoid, although not absolutely contraindicated. It's something to, you know, talk with your GI colleagues about in some cases.

The next category we have are the IL-12/23 and IL-23 inhibitors. Ustekinumab is an IL-12/23 inhibitor and we have two IL-23 inhibitors on the market, which are guselkumab (Tremfya, Janssen) and risankizumab (Skyrizi, AbbVie). All of these drugs are quite effective for skin involvement. Ustekinumab (Stelara, Janssen), risankizumab, and guselkumab all have lower numerically ACR20, 50, and 70 responses when you look at the trials compared to TNF inhibitors and to IL-17 inhibitors. Unfortunately, we don't have head-to-head data on these, but these are not, because of that, drugs I typically go to in people with more severe inflammatory arthritis at this time. I think more data will be forthcoming about this and I'm hopeful it may be reassuring, but at the moment I tend to utilize these as a second-line or first-line of people without a severe, you know, erosive disease from psoriatic arthritis.

The other thing to keep in mind is that in axial spondyloarthritis, risankizumab and ustekinumab both failed in treatment of this condition. There's a question still at this point as to whether axial psoriatic arthritis may represent a separate entity from typical axial spondyloarthritis and there will be data forthcoming in the next several years looking at the use of these IL-23 inhibitors with patients that have psoriatic arthritis with axial involvement as opposed to axial spondyloarthritis. However, as of now, I would argue the jury is currently out as to whether these medications are effective for patients with axial disease in the setting of psoriatic arthritis.

And so at this point, if one of the prominent domains is axial involvement, these tend to be medications that I put far down the line in favor of TNF inhibitors and IL-17 inhibitors, which have more proven efficacy in axial spondyloarthritis. Those drugs do, though, have an advantage of having a relatively low risk for infection compared to other biologic drugs. And in fact, in the trials of guselkumab and risankizumab, the risk for severe infection was no higher than seen in placebo, which is quite reassuring and makes these a really appealing option for patients that have risk for infection. I'll also point out that these are extremely effective for psoriasis and so for the patient with a quite severe psoriasis, IL-23 inhibitors are an excellent option.

The next category we look at are JAK inhibitors. There are two JAK inhibitors currently FDA-approved for use in psoriatic arthritis. The first is upadacitinib (Rinvoq, AbbVie) and the second tofacitinib (Xeljanz, Pfizer). Both of these medications have been shown to have efficacy for both psoriasis and for psoriatic arthritis, and both have also been shown to have efficacy in axial spondyloarthritis. So the presumption is they may have some role in patients with axial disease as well. The caution that comes up with these to some extent, particularly arises from the ORAL Surveillance trial of patients with rheumatoid arthritis. And it's worth keeping in mind that in patients with rheumatoid arthritis that were over the age of 50 and had cardiovascular risk factors, there was observed with tofacitinib, particularly at high doses of 10 milligrams twice a day, an increase in risk for major adverse coronary events and for certain malignancies.

Now it's unclear to what extent that applies in the psoriatic arthritis population, but I think it's worth keeping in mind that patients with psoriasis and psoriatic arthritis do have a higher cardiovascular risk at baseline. And so I think that's important to keep in mind when considering the use of tofacitinib in particular. Now that black box warning got slapped on both tofacitinib and upadacitinib, and so I do counsel my patients about that same safety signal in both drugs, even though we have not yet seen that safety signal arise in upadacitinib. Both of these are good options for patients with psoriasis and psoriatic arthritis and do definitely have a niche. The other one that's intriguing that's been FDA-approved now for psoriasis, but not yet for psoriatic arthritis is deucravacitinib (Sotyktu, Bristol Myers Squibb), which is the first selective tyk-2 inhibitor, which does appear to be effective in psoriasis and has a more favorable safety profile for my mind compared to what we see with upadacitinib and tofacitinib based on the clinical trials thus far. We need more data on this in psoriatic arthritis, but you know, in psoriasis, this is an appealing option.