Position Paper
Two considerations for patients with psoriasis and their clinicians:: What defines mild, moderate, and severe psoriasis? What constitutes a clinically significant improvement when treating psoriasis?,☆☆

*Present or past member of the Medical Advisory Board of the National Psoriasis Foundation. **Present or past member of the Board of the National Psoriasis Foundation.
https://doi.org/10.1067/mjd.2000.106374Get rights and content

Abstract

The definitions of psoriasis severity and clinically significant improvement in psoriasis are used to classify treatments, obtain Food and Drug Administration approval, and determine product labeling and reimbursement. The Medical Advisory Board of the National Psoriasis Foundation has addressed these issues because of their importance in the clinical trials that are conducted to gain FDA approval of indications. Narrow indications, which are without a sound rational basis, will—in this era of constant oversight by third party payers—affect physicians’ ability to manage patients with psoriasis. Body surface area (BSA) is usually used to define severity for clinical trials. It is not optimal for defining psoriasis severity because there are some patients with low BSA involvement who have very severe psoriasis and some patients with high BSA involvement who have mild psoriasis. We conclude that a quality of life (QOL) standard is better than BSA measurement for identifying patients with severe psoriasis. The second issue is what defines clinically significant improvement for patients with psoriasis. Setting an arbitrarily high criterion of clinical efficacy for new psoriasis treatments will likely limit the development and approval of useful treatments. To maximize the availability of useful psoriasis treatments, it is our thesis that psoriasis treatments should be approved when they have been shown to produce a statistically significant level of improvement in well-designed clinical trials. (J Am Acad Dermatol 2000;43:281-5.)

Section snippets

Severity of psoriasis: A view from the clinic

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Severity of psoriasis: A view from the new drug approval process

To further appreciate the significance of this position paper, it is necessary to understand the current drug approval process for the treatment of psoriasis. First, there are preclinical studies that demonstrate a profile of activity (eg, anti-inflammatory properties, antiproliferative properties, antiangiogenesis properties) which suggests the drug may have an effect on any or all aspects of the clinical manifestations of psoriasis. Phase II safety and dose-ranging trials in normal people or

The complexity of determining what constitutes severe psoriasis: An illustration

This issue can be appreciated by considering which of the following 4 patients has severe psoriasis:

  • Patient A: 20% BSA involved with psoriasis

  • Patient B: 10% BSA involved with psoriasis

  • Patient C: 5% BSA involved with psoriasis

  • Patient D: 1% BSA involved with psoriasis

Consider each of these patients with the following caveats:

  • Patient A has obvious widespread disease. This person’s disease is recognized by all as severe and therefore must alter the QOL. However, would it still be severe if it was

A QOL-based definition of the severity of psoriasis

Tables I to IV define psoriasis in a fashion that encompasses the patients’ perceptions (the varying ability of patients to accept side effects, the hassle of topical and ultraviolet light (UVL)–based treatments, the costs, and the lack of complete efficacy and toxicity of current treatments14, 15) and the prescribing habits of physicians. It is important to note that if there were an oral medication that worked every time, did not have associated side effects, and did not have

BACKGROUND TO WHAT CONSTITUTES CLINICALLY SIGNIFICANT IMPROVEMENT

The second purpose of this position paper is to bring attention to another important issue: “What constitutes clinically significant improvement (CSI)” in psoriasis? This is important both in clinical practice (medications that do not provide a particular patient a CSI are deemed not effective for that patient) and in regulatory decision-making (the FDA will not approve a treatment that does not provide a CSI). An attempt to define a CSI for clinical trials is a concept that is past due. The

CONCLUSION

Until we understand the molecular basis of psoriasis and have specific curative or consistently remittive therapies, the approving agencies should continue to assess new drug applications and approve those that are safe and demonstrate CSI in one or more end points. It is recognized that this invites approval of agents that will have limited beneficial effects. Perhaps the marketplace will effectively sort out those that are worthwhile from those that are not, but the current health care

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☆☆

Clinicians actively participating in clinical research trials on psoriasis and concerning the issues represented in this article.

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