The Evolving Spectrum of TNF Inhibitors in the Management of Psoriatic Disease - Episode 1

Pathogenesis of PsA and PsO

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Mark G. Lebwohl, MD, and Joseph F. Merola, MD, MMSc, discuss updates in the pathogenesis of PsA and PsO.

Mark G. Lebwohl, MD: Hello, and welcome to this Dermatology Times® DermView on “The Evolving Spectrum of TNF Inhibitors in the Management of Psoriatic Disease.” I’m Dr Mark Lebwohl. I’m the dean for clinical therapeutics at the Icahn School of Medicine at Mount Sinai in New York, New York and the chairman emeritus of the department of dermatology. Joining me is Dr Joseph Merola, an associate professor of dermatology and rheumatology at Harvard Medical School and the vice chair of clinical trials and innovation at Brigham and Women’s Hospital in Boston, Massachusetts.

In this video series, we’re going to review the relationship between psoriatic arthritis [PsA] and psoriasis, the differences in anti–TNF [tumor necrosis factor] molecules, as well as a patient case. Let’s get started. Joe, can you review the pathogenesis and association between plaque psoriasis and psoriatic arthritis? How can psoriasis progress to psoriatic arthritis?

Joseph F. Merola, MD, MMSc: Thanks, Mark. I’m delighted to be here. To begin, the vast majority of our patients with psoriatic arthritis start with psoriasis, more than 90%. One-third of our patients with psoriasis, we believe, go on to psoriatic arthritis. We know there are certain risk factors that increase the likelihood that a patient is going to develop psoriatic arthritis. That includes factors such as nail disease, inverse psoriasis, scalp psoriasis, more severe psoriasis, obesity, and family history of psoriatic arthritis, specifically in a first- or second-degree relevance. We know all of those, just as a level-setting exercise.

What’s interesting is that there’s shared pathogenesis between what we know is occurring in the skin and what seems to happen in the joints. There are genetic risk factors with some overlapping risk between the skin and joint disease. There are environmental factors that are less understood, that ultimately kick off this innate and adaptive immune response that we know of as psoriasis and ultimately psoriatic arthritis. The piece that we know less about is a very active, hot topic: what leads to that transition? What makes a patient go from predominantly skin disease into a psoriatic arthritis phenotype? We try to break that down into some preclinical asymptomatic phases into a more clinical phenotype, but we don’t know that. Something happens in that transition from skin to joint disease. That’s being worked out.

As dermatologists, we’re seeing patients who are at risk for developing psoriatic arthritis. We’re in the best position to be—as I’m sure we’ll talk about—screening for that disease, talking to our patients about that risk, and ultimately talking to them if they seem to be transitioning into PsA.

Mark G. Lebwohl, MD: That’s a great answer. I want to do 2 things because you got me thinking about seeing if something happens. Nobody knows, but all of us have seen when a patient is on a drug that might be controlling psoriatic arthritis that we didn’t know was there. When the patient was taken off that drug, arthritis came out. The example that we saw over and over, was when ustekinumab came on the market. Patients who were doing OK on TNF blockers but weren’t fully clear were switched to ustekinumab. We didn’t know they had psoriatic arthritis. Suddenly we started to think: is ustekinumab causing psoriatic arthritis? It didn’t, of course, but we had been suppressing arthritis with the TNF blockers. Withdrawal of certain therapies causes it.

I’ve seen psoriatic arthritis occur in patients who were treated for unrelated reasons with a systemic steroid, and as the steroid was tapered, the same thing happened. Arthritis came out, and so did psoriasis. We’ve seen that repeatedly. I have 1 more big-view comment: 70% of the time, psoriasis proceeds to arthritis; about 15% of the time, the 2 start together; and about 15% of the time, arthritis occurs ahead of psoriasis.

Transcripts edited for clarity