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PASI 100 and the perfection paradox

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By Warren R. Heymann, MD
June 27, 2016

I am not a psychiatrist, but over the years I have concluded that my patients’ happiness is more supratentorial than epidermal.

As we approach perfection, imperfections take on far greater importance. Some examples:

In medical school, I spent many Sunday afternoons in the stacks of the library of the Albert Einstein College of Medicine, scouring Index Medicus, finding a few relevant articles, photocopying them, and having a sense of accomplishment about the task. Now if it takes me more than 3 milliseconds to find a reference on PubMed, I can feel my blood pressure rise.

The smallest ding on a new car causes the greatest grief. A smashed bumper after 100,000 miles barely elicits a shrug.

If you stared at a Jackson Pollack painting, how would you know if he made a mistake? Alternatively, if you see a smudge on an otherwise white wall, it really stands out.

In the prebiologic era, methotrexate was the most common systemic agent that I used for my psoriatic patients. The goal was not to get them completely clear, but just enough to have a few plaques remain. That way you knew that you were not administering too much methotrexate thereby delaying future liver biopsies.

By analyzing data pooled from the nonplacebo arms of 3 phase III studies of brodalumab, Strober et al determined that PASI 100 is a clinically relevant end point, as complete skin clearance results in significant improvement in signs and symptoms of disease severity and health-related quality of life (1).

The bar is now raised — PASI 100 is psoriatic perfection. Previously, patients would be grateful for modest improvement in their disease; once the expectation (and potential reality) is complete clearance, how could anything less than PASI 100 be acceptable? Did you ever go to a movie that got stellar reviews only to feel disappointed because it wasn’t as entertaining as billed? If I spent $5000 on a ticket to see Hamilton, it damned well better be the best Broadway show ever (by the way, I bought the album for $23 and read Chernow’s book instead). Residual psoriatic plaques were formerly looked with a sense that patients have gotten so much better — now it is a source of frustration that they are still there.

PASI 100 is the new norm. Just think of the post-World War I tune: “How you gonna keep ‘em down on the farm, after they’ve seen Paree?”

1. Strober B, et al. Clinical meaningfulness of complete skin clearance in psoriasis. J Am Acad Dermatol 2016; 75: 77-82.

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