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Psoriasis: severity assessment in clinical practice. Conclusions from workshop discussions and a prospective multicentre survey of psoriasis severity

European Journal of Dermatology. Volume 16, Number 2, 167-71, March-April 2006, Clinical report

Summary

Author(s) : Joar Austad, John Berth-Jones, Frédéric Cambazard, Michel de la Brassinne, Knud Kragballe, Anders Ljungberg, Gillian Murphy, Kim Papp, Peter van de Kerkhof, Gottfried Wozel , Department of Dermatology, Rikshospitalet, Oslo, Norway, Department of Dermatology, Walsgrave Hospital, Coventry, UK, Service de Dermatologie, Hôpital Nord – CHU St. Etienne, St. Etienne, France, Service de Dermatologie, Université de Liegè, Liegè, Belgium, Aarhus Amtssygehus, Marselisborg Centret, Aarhus, Denmark, Dermatology Clinic, Karolinska Sjukhuset, Stockholm, Sweden, Beaumont Privat Clinic, Beaumont Hospital, Dublin, Ireland, Probity Medical Research Union, Waterloo, Ontario, Canada, Department of Dermatology, University Hospital Nijmegen, Nijmegen, The Netherlands, Klinik und Poliklinikum für Dermatologie, Universitätsklinikum Carl Gustav Carus, Dresden, Germany.

Summary : Psoriasis treatment is highly individualized. Although a standardized assessment of psoriasis severity for clinical practice may be theoretically advantageous for the purposes of determining treatment, the relevance of currently available research tools in clinical practice is uncertain. Our objectives were to ascertain in workshop discussions and through a prospective survey the relevance of standard severity measures in clinical practice with regard to choice of treatment. Although there was agreement on the possible structure of an algorithm for the treatment-related definition of psoriasis severity, consensus on the cut-off levels for the PASI and %BSA that would indicate a switch in treatment mode could not be reached.The lack of agreement prompted a prospective survey of 112 patients with psoriasis from 10 countries. This survey used a formal questionnaire asking for the PASI and %BSA scores, the patient’s self assessment score (VAS ranging from 0 to 10), location of the psoriatic lesions and disease phase. Severity scores from 20 patients pre-selected for inclusion in a trial of a biological agent were included for comparison. Severity scores were analysed in relation to the choice of treatment (topical or systemic, which included phototherapy and combination) suggested by the treating physician.PASI scores differed significantly between the treatment groups (topical vs systemic, p \= 0.009)\; however, there was large overlap in the range of PASI scores between the groups. The same was true for VAS scores (topical vs systemic, p \= 0.035). %BSA scores were not significantly different between treatment groups. There was a large overlap for both the topical and systemic treatment groups with the biologicals group for the range of both the PASI and %BSA scores. A standardized protocol for the evaluation of psoriasis severity based on established severity scores (PASI, %BSA) appears to be unrealistic in day-to-day clinical practice. In clinical practice, a host of factors must be evaluated alongside possible metric measures. This requires experience and the specialized medical education of those involved in the treatment of patients with psoriasis.

Keywords : biological agents, PASI, percent BSA, psoriasis, systemic treatment, topical treatment

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ARTICLE

Auteur(s) : Joar Austad¹, John Berth-Jones², Frédéric Cambazard³, Michel de la Brassinne⁴, Knud Kragballe⁵, Anders Ljungberg⁶, Gillian Murphy⁷, Kim Papp⁸, Peter van de Kerkhof⁹, Gottfried Wozel¹⁰

¹Department of Dermatology, Rikshospitalet, Oslo, Norway
²Department of Dermatology, Walsgrave Hospital, Coventry, UK
³Service de Dermatologie, Hôpital Nord – CHU St. Etienne, St. Etienne, France
⁴Service de Dermatologie, Université de Liegè, Liegè, Belgium
⁵Aarhus Amtssygehus, Marselisborg Centret, Aarhus, Denmark
⁶Dermatology Clinic, Karolinska Sjukhuset, Stockholm, Sweden
⁷Beaumont Privat Clinic, Beaumont Hospital, Dublin, Ireland
⁸Probity Medical Research Union, Waterloo, Ontario, Canada
⁹Department of Dermatology, University Hospital Nijmegen, Nijmegen, The Netherlands
¹⁰Klinik und Poliklinikum für Dermatologie, Universitätsklinikum Carl Gustav Carus, Dresden, Germany

accepté le 18 Octobre 2005

Traditionally, psoriasis treatment has been highly individualized, depending on the patient’s needs, but also varying from one medical school to another, even from one clinician to the next. Yet it can be argued that there may be an increasing need for a standardized treatment approach based on a standardized assessment of disease severity, categorizing patients into those with mild, moderate, or severe disease. This would allow the intensity of treatment, and thereby the treatment option, to be pitched according to the severity category.This communication by the Copenhagen Psoriasis Working Group (CPWG) presents the conclusions from two workshop meetings, held in December 2003 and October 2004, examining the arguments in favor of standardized psoriasis severity assessment and evaluating the reality of such standard assessments in daily practice in a prospective multicentre survey of more than 100 patients. The survey provided information on disease severity by the psoriasis area and severity index (PASI), percent body surface area involvement (%BSA), and patient self-rating on a visual analogue scale (VAS). Data from a set of patients pre-selected for inclusion in a clinical trial of a biological agent were included for comparison.The outcome of the workshop discussions and the results of the prospective survey contradict the need for a multipurpose standardized rating system to evaluate the severity of psoriasis. Rather, they emphasize that severity definitions are inevitably purpose-bound, and as such meaningful only in the context of their initial purpose. Also, categorization of disease severity in terms of disease management cannot be achieved by relying on a single metric tool or formula.Although standard measures of psoriasis severity, such as the PASI or %BSA, are undoubtedly useful in making management decisions, they cannot replace clinical experience, which must take into consideration a host of other factors not addressed by any one severity measure.

Need for standardization

Among clinicians, researchers and regulatory bodies, there is no universally accepted standard measure of disease severity in psoriasis. A wide range of disease severity definitions and metric tools for measuring clinical endpoints are available, including area involvement, sign scores, quality of life assessments, and summary scores [1, 2]. Indeed, Naldi and colleagues identified over 44 different scoring systems employed in 171 randomised clinical trials of psoriasis between 1977 and 2000 [3]. Even within commonly used metric tools, such as the PASI and %BSA, consistency is lacking. This heterogeneity poses a number of difficulties, which may seemingly be overcome by adopting a standard measure of disease severity.

Possibly most obvious is the problem of making a direct comparison of treatment efficacy across studies using different metrics or different severity definitions with the same metric, complicating the practising physician’s task of determining the best treatment for his patient. Feldman has recently addressed this problem by suggesting fixed PASI and %BSA cut-off values to define severe psoriasis for clinical trials. However, he conceded that this approach would exclude some patients with truly severe disease as defined by the impact of their disease on their quality of life (QoL) [4].

Given the chronicity of psoriasis, a standardized form of disease evaluation would also aid charting disease evolution and response to treatment over longer periods of time and across hand-over of care from one physician to another.

Finally, in view of the high costs of systemic treatment [5, 6] and the recent introduction of biological agents [7], third-party payment of healthcare costs and tightly managed health care budgets may lead to the imposition of spending limits linked directly to severity scores, thus requiring some objectivity and standardization.

Requirements of daily practice

The sheer volume of currently used or previously proposed severity measures is perhaps testament to the fact that no individual measure has so far been deemed universally suitable as a standard measure of psoriasis severity, and it is clear that such a measure would have to address a variety of points, such as those mentioned above. Furthermore the severity measure would have to be convenient for day-to-day use (i.e. the assessment tool should measure meaningful clinical improvement and be convenient to administer). By virtue of their wide-spread use, validity and consistency [1, 2], %BSA and the PASI assessments appear to be obvious candidates to form the basis of a standard measure of disease severity.

The advantages of %BSA, in which the area of one side of a flat closed hand represents 1% of the total body surface area, are that it is quick and convenient to use, with a low variability of test-retest statistics for the same observer (1%-2%). However, there is moderately high interrater variability and many %BSA-based methods are likely to overestimate the extent of psoriatic lesions and underestimate treatment efficacy [8]. Charting disease evolution over longer periods of time may also be prone to bias, as this relies on the observer’s recollection of previous estimates of the same patient. Percent BSA does not take into account erythema or pruritus, or induration, thickness, desquamation or scaling of the lesion.

The PASI, by contrast, combines physical signs and area of involvement in a single score. This metric has been used for over 25 years, is currently the most cited summary score, and has well-established validity (test-retest error < 2%). Drawbacks associated with the PASI are that physicians in practice may find it time-consuming to calculate and, more importantly, that it assumes a linear relationship between physical signs. The latter makes it an imprecise measure of changes at the extremes of the psoriasis severity range. This lack of sensitivity can distort the evaluation of disease improvement [2].

QoL is recognized as an important factor in determining the severity of psoriasis. Indeed, the severity of psoriasis has been described as first and foremost a QoL issue [9]. A survey by the National Psoriasis Foundation in the US clearly showed that individuals with psoriasis believe the disease to have a profound emotional and social impact on QoL, which has been likened in magnitude to that of cardiac disease and diabetes mellitus [10, 11]. As with metric tools, a great variety of QoL measures exist [12]. Among the simplest are VAS.

QoL scores are not without drawbacks. In chronic diseases such as psoriasis they may not necessarily represent actual changes in health or symptoms over time, but reflect psychological adaptation [13, 14]. QoL measures may also fall short of practicality in the clinical setting (e.g. lengthy questionnaires or elaborate psychometric tests), suitability for quantitative and comparative retrospective analyses and internal audit, and objective quantitative justification of treatment costs. A combination of physical and psychological measurements has been suggested for assessing disease severity and evaluating effectiveness of treatment [1, 15, 16].

Treatment-related severity assessment

In line with the above considerations, it should therefore be possible to assess psoriasis severity, and by extrapolation the type of treatment that is required, by integrating clinical scores (e.g. PASI or %BSA), QoL, and other modifying factors in a simple diagnostic algorithm of disease severity. Specifically defined disease severity could therefore be put into relation with broad treatment options. Members of the CPWG generally agreed that a patient’s perspective must form the basis of severity assessment, but that this must be tempered by an objective dermatological evaluation.

A number of modifying factors may impact on treatment choice. Some of the most important are listed below:

• Location of the lesions: involvement of visible or sensitive areas (hands, face, genitals, scalp), intertriginous regions, or areas that directly interfere with a patient’s work generally add to the severity of the disease.
• Disease phase: psoriasis would usually be considered more severe during a flare-up than during a stable phase.
• Joint involvement if present, would increase the severity rating.
• Treatment history, encompassing medical history and response to previous treatments, may not only modify perception of disease severity and management decisions but also predict the actual response to a new treatment.
• Patient perspective, including the patient’s expectations, goals and motivation regarding disease management may increase or decrease the psoriasis severity rating and impinge on management decisions.

Despite general agreement among the specialists at the CPWG workshops on the possible structure of an algorithm for the treatment-related definition of psoriasis severity, consensus on the cut-off levels for the PASI and %BSA that would be indicative of a switch in treatment intensity, could not be reached.

Opinions differed for the PASI, in particular, with suggestions for maximal cut-off values for ‘mild’ disease ranging from < 3 to < 7, and minimum cut-off levels for ‘severe’ disease ranging from > 10 to > 15. Opinion varied similarly for %BSA cut-off values.

Of concern was also that the choice of treatment may be limited de facto by the disease profile of the patient population included in the phase III clinical trials leading to drug approval.

The lack of agreement prompted a survey of 112 patients from seven centres. The aim was to determine in day-to-day clinical practice whether specific cut-off values of the PASI, %BSA, and a quality-of-life measure become apparent that relate to treatment choice; i.e. topical or classic systemic/combination therapy (which included phototherapy). Data of 20 patients who were enrolled in a trial of a biological agent were also included.

This survey was based on a formal questionnaire and was performed prospectively. Among other items, the questionnaire asked for the PASI and %BSA scores, the patient’s self assessment score (VAS ranging from 0 to 10), location of the psoriatic lesions and disease phase.

The questionnaire effectively provided a snap-shot of daily clinical practice, reflecting ‘real-life’ treatment decisions as they are made when a patient is seen for his/her initial consultation. Therefore, the population captured by this questionnaire is heterogeneous, including patients who may or may not be naive to treatment, and those who may be in different phases of their disease.

Survey results

Prospective data from 112 patients were included in the survey. PASI values were available for 92 patients (data not provided for 20 patients), %BSA values were available for 101 patients (data not provided for 11 patients), and VAS data for 79 patients (data not provided for 33 patients).

Treatment choice by PASI, %BSA and patient perception

PASI: Suggested treatment categories appeared to relate to disease severity as assessed by PASI. The difference between PASI scores and choice of topical or systemic/combination treatment reached statistical significance (p = 0.009).

However, the large overlap between the range of PASI scores for each treatment category did not allow the determination of distinct cut-off points, although there appeared to be a weak trend for increasing PASI scores to predict systemic/combination treatment as opposed to topical treatment ( (figure 1A) ).

BSA: The distribution of %BSA scores was very similar between chosen treatment categories, implying that assessment by this metric tool had limited influence on the physician’s choice of treatment type among this group of dermatologists ( (figure 1B) ).

Visual analogue scale: VAS scores representing the patient’s self-assessment of the severity of their psoriasis and its impact on QoL (on a scale of 0-10) were statistically not significantly different between topical and systemic/combination treatment categories ( (figure 1C) ). Insufficient data were available on this assessment measure in the biological treatment group.

The results of the survey indicate that psoriasis severity using PASI or %BSA assessment does not predict the type of treatment, topical or combination/systemic, that is chosen by clinicians.

Interestingly, the PASI and %BSA values for patients enrolled in the biologics trial appear to lie within the same range as those reported for patients for whom treatment with topical or systemic/combination therapy is suggested.

The overlap of PASI and %BSA values between a group of patients for whom topical treatment was judged suitable and patients fulfilling criteria for inclusion in a clinical trial with a biological agent appears paradoxal and throws up the question of how we define patients who require biologics, as cut-off values used in clinical trials may be misleading.

Location and disease phase

Other interesting observations to emerge from this survey were that the location of lesions was generally not by itself indicative of the type of treatment that was suggested by the clinician; although topical treatment was the treatment suggestion for over 60% of patients with psoriasis of the flexures. Furthermore, topical treatment was the suggested choice of treatment in approximately 60% of patients with a flare-up of their psoriasis, whereas this type of treatment was suggested for only approximately 30% of patients with chronic psoriasis.

Implications of the survey

We acknowledge that this survey has limitations and generates many questions. The sample size of this multicentre survey restricts the degree to which extrapolations can be made. Specifically, there was a clear effect of centre (country) on treatment choice. This may have been additionally compounded by a small number of patients who were pre-selected for inclusion in clinical trials.

Nonetheless, it is possible to draw at least provisional conclusions which are endorsed by the CPWG as the result of their workshop discussions and survey. For one, it has become clear that simply adopting established PASI and %BSA cut-off levels for disease severity bands that were devised specifically for the purpose of drug approval in clinical trials does not accurately reflect the clinical reality of psoriasis severity. In practice, disease severity is dependent not only on area involvement and sign scores, but also on the location of the disease, response to previous treatment, patient history, and the patients’ perception of their disease and quality of life (QoL). It is important to distinguish between severe psoriasis in terms of how badly it affects the skin and psoriasis that severely affects quality of life.

It is also clear that patients defined as suffering from mild, moderate, or severe psoriasis by virtue of a metric tool such as the PASI or %BSA must be distinguished from patients who merit treatment with topical, systemic/combination, or biological therapy, respectively. These categorisations are not interchangeable. Grouping patients into categories of mild, moderate, or severe disease cannot be done without a clear purpose in mind. Categorisation is purpose-bound and therefore must be reassessed if the purpose changes, for example, from the question of “Should patients be seen by an expert?” to the question of “Who should receive treatment with systemic or biological agents?”

The findings of the survey support these ideas. Although there appears to be a trend for increases in the PASI scores to correlate with increases in treatment intensity (from topical to systemic treatment), no definite cut-off points for treatment categories are discernable. Furthermore, the overlap between the metric scores of the treatment categories ‘topical’ and ‘systemic/combination’ and the metric scores attained by patients destined for treatment with a biological agent are substantial, underlining the notion that, although the PASI and %BSA are useful outcome measures in clinical trials, they are perhaps less suitable for determining treatment in clinical practice.

Concluding remarks

Do these results indicate that %BSA and PASI are obsolete measures of disease severity in clinical practice? Not entirely. The measures patently provide valuable guidance, but it is also clear that they are not sufficient by themselves to explain treatment choice. Modifying factors and their interpretation by clinicians appear to be the key in guiding treatment. For this, physicians require experience and relevant teaching. Indeed, in the experience of the CPWG, it appears that many experienced specialists evaluate patients by eye and rarely resort to the PASI or %BSA scores for guidance. Exceptions are the evaluation of new patients or the requirement for a tracking system. More inexperienced physicians will also find evaluation by PASI or %BSA helpful in guiding initial management.

A standardized protocol or mathematical model for the evaluation of psoriasis severity in day-to-day clinical practice, however, appears to be unrealistic.

The consensus arising from the CPWG workshops is that psoriasis severity depends on the purpose for which it is evaluated. In clinical practice, a host of factors must be evaluated alongside possible metric measures. Evaluating rationally and carefully all these factors, which will be weighted differently depending on the individual patient’s circumstances, requires experience and the specialized medical education of those involved in the treatment of patients with psoriasis.

This manuscript was supported by an unlimited educational grant from LEO Pharma.

References

1 Weisman S, Pollack CR, Gottschalk RW. Psoriasis disease severity measures: comparing efficacy of treatments for severe psoriasis. J Dermatolog Treat 2003; 14: 158-65.

2 Ashcroft DM, Li Wan Po A, Williams HC, Griffiths CEM. Clinical measures of disease severity and outcome in psoriasis: a critical appraisal of their quality. Br J Dermatol 1999; 141: 185-91.

3 Naldi L, Svensson A, Diepgen T, et al. Randomized clinical trials for psoriasis 1977-2000: the EDEN survey. J Invest Dermatol 2003; 120: 738-41.

4 Feldman SR. A quantitative definition of severe psoriasis for use in clinical trials. J Dermatolog Treat 2004; 15: 27-9.

5 Finzi AF, Mantovani LG, Belisari A, Italian Association for Studies on Psoriasis. The cost of hospital-related care of patients with psoriasis in Italy based on the AISP study. Associazione Italiana Studi Psoriasi. J Eur Acad Dermatol Venereol 2001; 15: 320-4.

6 Feldman SR, Fleischer Jr. AB, Reboussin DM, et al. The economic impact of psoriasis increases with psoriasis severity. J Am Acad Dermatol 1997; 37: 564-9.

7 Dubin DB, Tanner W, Ellis R. Biologics for psoriasis. Nature Rev 2003; 2: 855-6.

8 Ramsay B, Lawrence CM. Measurement of involved surface area in patients with psoriasis. Br J Dermatol 1991; 124: 565-70.

9 Krueger GG, Feldman SR, Camisa C, et al. 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? J Am Acad Dermatol 2000; 43: 281-5.

10 Krueger G, Koo J, Lebwohl M, et al. The impactof psoriasis on quality of life. Results from a 1998 National Psoriasis Foundation Patient-Membership survey. Arch Dermatol 2001; 137: 280-4.

11 Rapp SR, Feldman SR, Exum ML, et al. Psoriasis causes as much disability as other major medical diseases. J Am Acad Dermatol 1999; 41: 401-7.

12 Finlay AY. Quality of life measures in dermatology: a practical guide. Br J Dermatol 1997; 136: 305-14.

13 Ashcroft DM, Li Wan Po A, Williams HC, Griffiths CEM. Quality of life measures in psoriasis: a critical appraisal of their quality. J Clin Pharm Ther 1998; 23: 391-8.

14 Muldoon MF, Barger SD, Flory JD, Manuck SB. What are quality of life measurements measuring? Br Med J 1998; 316: 542-5.

15 Kirkby B, Richards H, Woo P, et al. Physical and psychologic measures are necessary to assess overall psoriasis severity. J Am Acad Dermatol 2001; 45: 72-6.

16 Gottlieb AB, Chaudhari U, Baker DG, et al. The National Psoriasis Foundation Psoriasis Score (NPF-PS) system versus the Psoriasis Area Severity Index (PASI) and Physician’s Global Assessment (PGA): a comparison. J Drugs Dermatol 2003; 2: 260-6.