C C Jacobson1, A B Kimball. 1. Department of Dermatology, Stanford University School of Medicine, 900 Blake Wilbur Drive, W0024, Stanford, CA 94305, USA.
Abstract
BACKGROUND: The Psoriasis Area and Severity Index (PASI) is the most frequently used clinical severity scale in clinical trials. Drug approval often depends on a 75% improvement in the baseline PASI score, also known as a PASI 75 or Delta PASI 75. This benchmark may be an overly stringent way to determine the success of psoriasis treatments as Delta PASIs appear to under-represent true clinical improvement. This discrepancy may relate to the way numerical values are assigned to the degree of body surface area (BSA) involvement. OBJECTIVES: To assess whether altering the BSA component of the PASI formula so that it is weighted more heavily will result in a calculated change in psoriasis severity that more closely reflects patient assessment of improvement. Models developed included the Psoriasis Log-based Area and Severity Index (PLASI), which assigns values to the BSA score based on a linear scale using logarithms to define the intervals, and the Psoriasis Exact Area and Severity Index (PEASI), which uses the actual BSA as the multiplicative factor in the area score. METHODS: Data were abstracted retrospectively from two clinical trials involving psoriasis treatments that used the PASI. The same trained psoriasis graders were involved in both trials. In these trials, baseline and end-point PASI worksheets were completed that included the actual clinician-estimated BSA involvement (0-100%) for each of the four areas (head, upper extremities, trunk and lower extremities). In one of the trials, patients were asked to assess the percentage improvement in their psoriasis at the end of the treatment window. PASIs and Delta PASIs were recalculated based on the new models and all scoring systems were validated by analysing their relationship to patients' self-assessments. RESULTS: Clinical improvements under the new grading systems translated into greater percentage changes than calculated using the Delta PASI formula. Specifically, the Delta PASI 50 translated to a Delta PLASI 57.2 and Delta PEASI 61.1; Delta PASI 75 was equivalent to Delta PLASI 85.7 and Delta PEASI 91.7. Importantly, Delta PASI tended to be systematically lower than patients' self-assessment, while Delta PLASI and Delta PEASI better matched patients' self-assessments using a best-fit model. CONCLUSIONS: These results suggest that the Delta PASI underestimates percentage improvement when compared with measures of patient's self-assessment, while Delta PLASI and Delta PEASI correlate better. Prospective studies will have to be performed to confirm these relationships, but weighting BSA more heavily in the severity score may result in a more accurate reflection of clinical status.
BACKGROUND: The Psoriasis Area and Severity Index (PASI) is the most frequently used clinical severity scale in clinical trials. Drug approval often depends on a 75% improvement in the baseline PASI score, also known as a PASI 75 or Delta PASI 75. This benchmark may be an overly stringent way to determine the success of psoriasis treatments as Delta PASIs appear to under-represent true clinical improvement. This discrepancy may relate to the way numerical values are assigned to the degree of body surface area (BSA) involvement. OBJECTIVES: To assess whether altering the BSA component of the PASI formula so that it is weighted more heavily will result in a calculated change in psoriasis severity that more closely reflects patient assessment of improvement. Models developed included the Psoriasis Log-based Area and Severity Index (PLASI), which assigns values to the BSA score based on a linear scale using logarithms to define the intervals, and the Psoriasis Exact Area and Severity Index (PEASI), which uses the actual BSA as the multiplicative factor in the area score. METHODS: Data were abstracted retrospectively from two clinical trials involving psoriasis treatments that used the PASI. The same trained psoriasis graders were involved in both trials. In these trials, baseline and end-point PASI worksheets were completed that included the actual clinician-estimated BSA involvement (0-100%) for each of the four areas (head, upper extremities, trunk and lower extremities). In one of the trials, patients were asked to assess the percentage improvement in their psoriasis at the end of the treatment window. PASIs and Delta PASIs were recalculated based on the new models and all scoring systems were validated by analysing their relationship to patients' self-assessments. RESULTS: Clinical improvements under the new grading systems translated into greater percentage changes than calculated using the Delta PASI formula. Specifically, the Delta PASI 50 translated to a Delta PLASI 57.2 and Delta PEASI 61.1; Delta PASI 75 was equivalent to Delta PLASI 85.7 and Delta PEASI 91.7. Importantly, Delta PASI tended to be systematically lower than patients' self-assessment, while Delta PLASI and Delta PEASI better matched patients' self-assessments using a best-fit model. CONCLUSIONS: These results suggest that the Delta PASI underestimates percentage improvement when compared with measures of patient's self-assessment, while Delta PLASI and Delta PEASI correlate better. Prospective studies will have to be performed to confirm these relationships, but weighting BSA more heavily in the severity score may result in a more accurate reflection of clinical status.