Erin L. Arnold, MD, FACR, of Orthopaedics and Rheumatology of the North Shore in Skokie, IL, discusses evolving treatment strategies and the use of biologic therapies in the management of psoriatic disease.
AJMC®: How would you characterize psoriatic disease from a quality-of-life standpoint?
Arnold: It is important to differentiate, because skin psoriasis is often an easier diagnosis to make than psoriatic arthritis. A large percentage, around 40%, of patients with skin psoriasis most likely have psoriatic arthritis, and one of the most frustrating aspects, I believe, for patients is that there is no way to adequately diagnose psoriatic arthritis; therefore, delays in diagnosis are regular. This is relevant because we know [that] the greatest risks for patients with psoriatic arthritis [include] cardiovascular implications, a prolonged exposure to inflammation, and an inadequate initial therapy and aggressive therapy. So, the longer it takes to diagnose these patients, the more damage presumably they have and the greater their risk of comorbidities. I would often describe journey of the patient with psoriatic as demoralizing and frustrating because no one understands their inflammatory disease, and it’s very difficult for people, including some rheumatologists, to make the diagnosis.
The most interesting group of patients and often the most underserved are those with psoriatic arthritis who don’t yet have skin psoriasis. This is a very difficult group of patients [in terms of diagnosis] but, to me, a particularly interesting group of patients.
I’m a clinical rheumatologist in solo private practice, and in my practice, we are very aggressive in trying to understand patients’ arthralgia and joint symptoms and look for multiple ways to help us differentiate between an arthritis that’s driven by the immune system and inflammation versus an osteoarthritis or crystal arthropathy. The data regarding cardiovascular disease risk are very compelling, but I also think compelling data show that the faster you can control their inflammatory disease, the higher the likelihood of exposing them to a reduced number of medications and maybe ultimately no medication. So, we’re very aggressive in our approach to these patients. It’s hard for people to get to me, as a rheumatologist, not just because there aren’t many of us but also because patients are not appropriately referred by their other physicians. So, by the time somebody comes to me with joint pain, it’s really my job to prove they don’t have inflammation. I assume up front that they do, and I have to prove that they don’t.
AJMC®: How important is it that dermatologists and primary care physicians ask patients with skin psoriasis questions about joint pain?
Arnold: With the dermatologists I work with, we are very forthright at communicating the importance of screening their patients with skin psoriasis for inflammatory joint pain. Some simple questionnaires can help assess if patients are at risk or at least should be considered for referral. I think it’s tremendously important to not just see the patient for their skin disease. Often the skin is just a manifestation of things that are happening deeper, so we encourage all the dermatologists who refer to me to assess patients’ inflammatory joint disease. I think it’s incredibly overlooked, and I think that it’s very important.
AJMC®: Has your approach to treating patients with psoriatic arthritis changed since the development and proliferation of biologic therapies for diseases such as psoriatic disease?
Arnold: I think a disease-modifying medication like methotrexate, sulfasalazine, or leflunomide should be considered as a therapy to be added to biologic therapy, not as a first-line therapy. That’s different with how I approach my patients with rheumatoid arthritis [RA], but the caveat here is that patients with psoriatic arthritis have a greater risk of morbidity associated with the disease-modifying medications, specifically methotrexate and leflunomide, with regard to liver disease, and so those are not typically first-line therapies in my practice. In my patients with RA, all are on methotrexate; but with my psoriatic arthritis patients, I’m much more likely to use a biologic therapy or something like apremilast, which has a place in treating predominantly skin psoriasis but also [has] some pretty good outcomes in peripheral arthritis. I think of these patients a little bit differently than I think of my patients with RA. I think of them more like I do my patients with ankylosing spondylitis arthritis, who really don’t have much benefit when starting with a first-line disease-modifying therapy. You wouldn’t do that in those patients, either, so it’s really transformed the way we are able to treat these patients.
AJMC®: What factors do you consider when selecting treatment?
Arnold: The first thing I want to get into is the cardiovascular disease data, because in this group of patients, the risk is incredibly impressive. When you look at the cost associated with therapy, I think it’s equally important to look at [the cost of] inadequately treating these patients. It is really relevant from a physician standpoint to think about what I can prevent with certain medication. So, just to put that in context, we don’t really have patients anymore with RA, psoriatic arthritis, in the hospital, which is incredibly different from even a couple of decades ago.
I have the greatest experience with the TNF [tumor necrosis factor] inhibitors, and I think that those can be very useful in patients with skin disease and joint disease. If I see patients who have predominantly skin disease and a little bit of mild peripheral joint disease, I might consider initial trial of apremilast. If I have patients, though, who have pretty impressive joint disease and skin disease, often a TNF inhibitor can be the first therapeutic intervention. If they failed a TNF, then I’d quickly switch to an IL-17A [interleukin 17A] inhibitor, like secukinumab or ixekizumab, and I don’t think there are really a lot of good data to suggest that if you fail one TNF, you should try another TNF. I think that was something we did when we didn’t have other therapies that were more disease specific available.
Ustekinumab is another medication that I might consider in a patient who has a bad skin disease and less joint disease, if they fail something like ixekizumab or can’t tolerate it from a GI [gastrointestinal] standpoint. So, that would be another one I would use for predominantly skin and, to a lesser degree, joint disease. Some of it is about how much joint disease they have compared with how much skin disease they have. In patients with spondylitis and, more specifically, sacroiliitis associated with their psoriasis, I’m choosing a TNF or an IL-17A inhibitor. [It’s important to] look at the comorbidities that they have associated with their arthritis, and then we look at the skin disease they have compared with their pattern of arthritis, spine vs peripheral joints.
If I were given the opportunity to use the IL-17A inhibitor as a first-line therapy, I might consider that. We use the TNF as a first-line therapy because that’s what’s directed by insurance; I don’t think it’s necessarily because that is clinically the most correct thing to do. I think the IL-17A inhibitors are a more disease-specific targeted medication, and that is spectacular.
AJMC®: Do you see the guidelines evolving enough based on continued data to allow the use of IL-17 inhibitors in the first-line setting?
Arnold: Although the data are relevant, what turns out to be equally important is the pricing of these agents. Having more data available will help support what I think is already apparent: that we should use these disease-specific medications to treat the disease. But the cost picture is a complicated web that involves the pharmacy benefit managers, the drug companies themselves, and the insurers. The simplest way to look at it is from what the patient and the physician care about: What’s going to treat their disease? The more data we have, the more I think we’ll start to see that these disease-specific medications really do have some superior benefit.
AJMC®: What do you feel are the most significant unmet needs in managing psoriatic arthritis and psoriatic disease more generally?
Arnold: The No. 1 unmet need is diagnosis and understanding burden of disease activity [inflammation]. No specific blood test definitively rules in or rules out a diagnosis of RA, psoriatic arthritis, or ankylosing spondylitis. Instead we use a compilation of measures—whether it is imaging derived, patient derived, clinically derived—to make a diagnosis and understand inflammation burden. This is especially true in psoriatic arthritis, where we don’t have any antibody tests to help make the diagnosis.
We also don’t yet have an objective measure that you can follow over time that best predicts risks of progression of the disease. We do have some things in RA that help us do that, but it’s not as well played out in psoriatic arthritis, and to have a reliable measure that you can follow is so helpful. Imaging studies are being evaluated, as are disease activity and clinical measures, but I think we need an objective measure that we can follow to assess whether patients are responding to therapy.
Another equally important consideration in these patients: How do we address comorbidities? In psoriatic arthritis and skin psoriasis, a large amount of patients suffer from obesity, and often in a rheumatology clinic, we aren’t equipped to really help them lose weight. Helping patients lose weight turns out to be incredibly important. Also, tobacco use in this group is relevant. Obese patients with psoriatic arthritis would never respond as well and would have poor outcomes simply because of their obesity compared to nonobese patients with psoriatic arthritis, and patients who smoke will not have as good of an outcome and a response to therapy compared to matched patients with psoriatic arthritis who don’t smoke. So, addressing those comorbidities is really important.