Moving Beyond PASI

The Psoriasis Area Severity Index (PASI) was first introduced into our dermatology lexicon in 1978 by Frediksson and Pettersson, who were evaluating a new oral retinoid (etretinate) for the treatment of psoriasis. Since then, we have seen PASI 50, 75, 90, and 100 being utilized in clinical trials to explain the percentage of PASI improvement that a subject obtains within a certain timeframe, i.e. 12,16, 52, or more weeks.

When a clinician thinks about a PASI improvement, what goes through their mind? Are they thinking that the average baseline PASI in a clinical trial is 22.5 or that a standard endpoint of 75 percent improvement (PASI 75) would be 5.625? And what does a PASI 5.625 really mean, anyway? Did the body surface area (BSA) improve from 20 percent to five percent? Did the physician global assessment (PGA) improve from moderate to mild or almost clear?

In other words, was the improvement correlated to a change in BSA, severity of disease, or both? It is quite difficult to conceptualize the degree of the patient’s psoriasis other than to infer an overall percentage improvement. Furthermore, and maybe more importantly, the vast majority of dermatologists won’t do a PASI when evaluating psoriasis patients in their office, because of its time consumption. Hence there is a disconnect between the assessment in clinical trials and in the exam room.

When PASI Falls Short

In addition to the difficulties in conceptualization, there are some rather large gaps in PASI assessment. Let’s review the PASI scoring methodology.  

The body is divided into four regions with a respective area percentage:

Head and neck = 10 percent

Trunk = 30 percent

Arms = 20 percent 

Legs (including buttock and genital area) = 40 percent.

Each area is evaluated for erythema, induration and scale on a 0-4 scale where: 

clear = 0,

mild = 1,

moderate  = 2,

severe = 3, and

very severe = 4.

So far so good, However, when evaluating the extent of each body region covered with psoriasis, the valence it is given is:

0 = clear,

1 = 1-9 percent,

2 = 10-29 percent,

3 = 30-49 percent,

4 = 50-69 percent,

5 = 70-89 percent, and

6 = 99-100 percent.  

Having fun yet?

It’s no wonder clinicians don’t do PASIs in their offices.

Let’s consider a patient with plaques assessed with a scale = 2, erythema = 2 and induration = 2, i.e. all moderate. Now let’s assume the patient has psoriasis on 10 percent of each of the four regions. The PASI would be 12.

Another patient also has scale = 2, induration= 2, and erythema= 2, but he has psoriasis on 25 percent of his body resulting in the same PASI score of 12.

Hence, someone with 10 percent BSA and moderate plaques has the same PASI as someone with 25 percent BSA and moderate plaques. There is clearly a problem with this metric.

PASI may make even less sense when evaluating patients who present with less than moderate-to-severe psoriasis seen often in psoriatic arthritis trials or topical therapy trials, where BSA tends to be less than 10 percent. For example, a patient with 10 percent of the arms (two palms) would have the same valence of 2 as a subject who had 15 percent (three palms). If both patients had moderate plaques, the PASI would be 2.4 for both patients even though the second had 50 percent more psoriasis on their arms. Hence subject No. 2 would have to improve 50 percent more to show the same PASI improvement as subject No. 1.

In addition to these pitfalls, there is no assessment of quality of life, pruritus, loss of sleep, anxiety, depression, or treatment satisfaction within the PASI.

What other objective measures could be used that make more sense, intuitively, experimentally, and practically? The PGA is based on the average erythema, induration, and scale of all the plaques in which O = clear, 1= almost clear, 2 = mild, 3 = moderate, and 4 = severe.

PGA X BSA

PGA and BSA have been utilized in both clinical trials and private practice. Individually they have their inadequacies, i.e., a patient could initiate treatment with 20 percent BSA and a PGA of 4 (severe) and after 12 weeks of treatment the BSA decreases to 2 percent but the PGA decreases only to 3 (moderate). BSA ranges from 0-100 percent.

If a clinician were assessing psoriasis severity based only on PGA, he or she would note very little change even though there was a 90 percent improvement in BSA. This can also be noted where there is a significant decrease in PGA, but a small change in BSA.

The product of PGA and BSA has been utilized and proven to be an effective method to evaluate psoriasis improvement. The product of BSA x PGA = 0-400.

Let’s look at some examples: A patient has BSA of 20 percent (one fifth of their body covered with psoriasis) and a PGA of 3 (moderate) for a score of 60.

After 12 weeks of treatment, the BSA = five percent and PGA = 2 (mild) for a score of 10.  The improvement of the product from 20 percent (moderate) to five percent (mild) is 84 percent. Another example patient has a BSA = 5 and a PGA =3 (moderate) for a score of 15. After 12 weeks, the BSA= 2 and the PGA=2 (mild), resulting in a total score of 4 or a 75 percent improvement. 

This change would not have been picked up in PASI, because five percent and two percent both have the same valence of 1.  It also seems easier to comprehend the change from baseline when using BSA x PGA as there is a basic understanding of what 20 percent looks like.

One palm equals one percent, which means a PGA of 3 (moderate) and a BSA of five percent means much more so than PASI 20 or PASI 40. PGA x BSA is linear. Ten percent of the leg and 25 percent of the leg does not equal the same as it does in PASI.

The Need for a Subjective Psoriasis Measure

Even if PGA x BSA proves to be a better objective metric of evaluating psoriasis than PSA, we still require a subjective coefficient to determine the patients response to therapy.  In some cases, smaller areas such as the palms, soles, scalp and genital area have a dramatic impact on quality of life, and neither PGA x BSA or PASI will capture this burden of disease. Some patient reported outcome (PRO) measure needs to be incorporated into the PGA x BSA paradigm.  The dermatology life quality index (DLQI) indicates the most severe impact on the quality of life. Regardless of the questionnaire that is chosen to represent subjective symptoms, i.e. pruritus, pain, fatigue, loss of sleep, my hope is to find a PRO that accurately assesses all psoriasis patients so that a composite objective-subjective measure can be used in their evaluation and to monitor the effects of therapy. n

Jerry Bagel, MD is Director of the Psoriasis Treatment Center of Central New Jersey.

Elise Nelson, LPN is the full-time clinical research manager and coordinator at the Psoriasis Treatment Center of Central New Jersey.

1. Walt JA, et al. “Product of PGA and BSA: a simple static measure of psoriatic severity in a longitudinal cohort,” Journal of the American Academy of Dermatology, 2013: 931-937

2. Robinson A, et al. “Physician Global Assessment (PGA) and Psoriasis Area and Severity Index (PASI): why do both? A systematic analysis of randomized controlled trials of biologic agents for moderate to severe plaque psoriasis.” Journal of the American Academy of Dermatology, 2012 p 369-374.

3. Lubrano E, et al. “Measuring psoriatic disease in clinical practice,” Autoimmune Review, 2015: 864-874