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Management of Psoriatic Arthritis With Biologics

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Anthony M. Turkiewicz, MD:Let’s discuss the biologic or advanced therapies that are available for psoriasis and psoriatic arthritis. Interestingly, when these first came out in the TNF [tumor necrosis factor] world, some were for psoriatic arthritis and then got approved for psoriasis. Then just the dermatologists had this trend that psoriasis has been the first indication, followed by psoriatic arthritis, to go beyond the discussion we’re having today. We’ll start by naming the classes or the mechanism of action [MOA] families and then the individual therapies. We know that TNF inhibitors, including golimumab, certolizumab, adalimumab, are the initial therapies, the go-to therapies, and for some they remain for our psoriatic arthritis and their ability to cover the gamut.

The second MOA family, obviously the interleukin-17a inhibitors, is currently available: secukinumab and ixekizumab, which are both approved for psoriatic arthritis and psoriasis. More recently approved for us in the rheumatology world—dermatologists have it for similar use—is guselkumab, the IL-23 inhibitor. Prior to that was the IL-12/23 inhibitor of ustekinumab. For a high-level overview of T-cell costimulatory blockade of abatacept and a Janus kinase inhibitor, tofacitinib is the only drug approved for PsA [psoriatic arthritis]; others are likely to come out. Those are the 5 families, or 5 mechanisms of action. We’ll start with very high level key points on efficacy and safety of these various classes of drugs in psoriatic arthritis. If it’s OK, Hillary, we’ll start again giving the broad TNF umbrella. Can you go over some of the key points? Is there any difference among them in the treatment of psoriatic arthritis?

Hillary E. Norton, MD: We have extensive experience using the TNF inhibitors for psoriatic arthritis and for psoriasis. These have been primarily the go-to biologics for many years prior to getting our newer therapies. We do have data for all the different domains for TNF inhibitors, so we know they treat the peripheral arthritis, axial disease, dactylitis, enthesitis, and nails. That is important in our guidelines to tell us to start with TNF inhibitors after patients have done DMARDs [disease-modifying antirheumatic drugs] or, in some cases, gone directly to TNF inhibitors in the case of axial disease. This is where we really take the comorbidities into account because if somebody has inflammatory bowel disease or uveitis, we might want to use a monoclonal antibody because we’ve got data there.

There are safety issues. This is where we’ll talk about safety advantages with more therapies, because we have more options. The TNF inhibitors do have a box warning for infection and malignancy, and there are some other issues. For decompensated heart failure or a history of demyelinating disease, we don’t want to use TNF inhibitors. There are a lot of advantages. We have to take into account that particular patient and their comorbidities and safety issues for the newer therapies that are starting to come into play.

Anthony M. Turkiewicz, MD: Thank you. John, similar question: Can you give us an overview about the safety of the class, the interleukin-17a inhibitors? Can you touch on that?

John Tesser, MD: It’s remarkable what’s happened in the last 5 years or so in this space. We had only TNF inhibitors as advancements on top of our conventional DMARDs, and now we have all these others. The 17a inhibitors were the first ones after the TNF inhibitors, and we have 2 that have been approved that you alluded to: secukinumab and ixekizumab. They are effective for the psoriatic arthritis component of the disease, but they’re not more effective than TNF inhibitors. In fact, when we look at psoriatic arthritis, we see that with the newer agents that are demonstrating incredible effects on skin, we still can’t break that barrier of joint improvement, the same barrier we’ve hit with rheumatoid arthritis [RA].

What’s incredible is what happens to the skin. As Steve knows very well, we’re seeing PASI [Psoriasis Area and Severity Index] scores, we’re talking about PASI scores of 90%, even 100%. PASI 90 scores of 70-plus percent improvements. But for joint improvements, ACR20 [American College of Rheumatology 20% improvement], ACR50 [American College of Rheumatology 50% improvement], and 70 [American College of Rheumatology 70% improvement] are not much better than the mid-50s, 30s, and about 20, which is what we’re used to. They’re effective, and sometimes you hit a home run—somebody gets an incredible response with their joints. But most people going on them are going to get this average response.

As for their safety, this is really a feather in the cap of this class. They are safe agents. There are a couple of things we must be aware of. There are the few patients who may develop colitis or may, if they’ve had a history of colitis, have an exacerbation. It is important to exercise caution and not take someone with active colitis. But it is not wrong or contraindicated to try to use them if someone has had a history of colitis, but just watch them very carefully.

The only other minor thing called out in the label of the drugs—and they don’t have a black-box warning about them, which is important—is the issue of fungal infections. It’s not a huge issue. It’s something in the background that one needs to be aware of and monitor. Accepting for other tolerability issues and other issues like minor infections and such, these agents are very safe and are definitely a welcome to our armamentarium to treat the disease.

Anthony M. Turkiewicz, MD: It has provided that effectiveness from a skin perspective but also for the TNF experience with the manifestations. Touching on the Janus kinase and even the T-cell costimulatory blocker, I consider these discussions to make this a comprehensive program. I say that specifically with abatacept. I’m not commenting on how to use or not use. But in my opinion, it came out with very little fanfare in the summer of 2017, when the abatacept article came out. There were 400 psoriatic arthritis ACR scores in the 40% range, compared with placebo in the 20% range. Safety was no different in PsA from what we saw in RA. I just want to throw it out to John: Was there much fanfare with abatacept when it came out for PsA?

John Tesser, MD: No. It was approved about the same time the IL-17s were taking off and everybody saw the data there.

Anthony M. Turkiewicz, MD: Hillary, do you agree with that?

Hillary E. Norton, MD: Yes, absolutely.

Anthony M. Turkiewicz, MD: Tofacitinib had been the first JAK approved for psoriatic arthritis and they had a far more structured approach with 2 separate trials: a TNF experience and TNF naїve. I’ve seen good data on joint at the lower dose. Of course in early 2019, the FDA was sending out letters for us to keep an eye out for oral surveillance, which may have had somewhat of an effect on usage. But some rheumatologists felt that tofacitinib has been a helpful player in the armamentarium of psoriatic arthritis. Any comments on that, John or Hillary, with regard to the Janus kinase use? What’s available in PsA in your world?

John Tesser, MD: My thoughts in general are that they take a second. At least tofacitinib has taken a second line to the newer agents that have come out. I wouldn’t choose tofacitinib as a first therapy after conventionals over TNF or IL-17s. I would probably try both of those first and then go to that if I needed to. Except for 1 thing, which is your decision-making. If a patient wants a pill, the patient should get a pill.

Hillary E. Norton, MD: Absolutely. That’s where it plays the biggest role in my practice. This is not something I’m going to reach for first or second line. This is something I’m going to use if the patient fails multiple therapies and we’re looking for another MOA. But patients do sometimes request it simply because they want an oral agent.

Transcript Edited for Clarity


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