A 50% reduction in the Psoriasis Area and Severity Index (PASI 50) is a clinically significant endpoint in the assessment of psoriasis

A 75% reduction in the Psoriasis Area and Severity Index (PAST) score (PAST 75) is the current benchmark of primary endpoints for most clinical trials of psoriasis. Many consider this endpoint to be too stringent as it places potentially useful therapies at risk of failing to demonstrate efficacy. We hypothesized that a 50% reduction in the PAST score (PAST 50) represents a meaningful change in a person's life and thus is a better primary endpoint. To test this hypothesis, we analyzed PAST scores, quality of life (QoL) data, and desired re-treatment scores from a number of clinical trials in addition to studying individual elements that make up the PAST. This analysis shows (1) the PAST score is not linearly reflective of psoriasis severity (eg, a reduction in area of 95% without a change in redness, scaliness, and induration translates to only a 66% reduction in PAST); conversely, a drop in erythema, scale, and induration from an average of 3 to I would not lead to a 75% reduction in PAST; (2) treatment with methotrexate, an effective psoriasis therapy, more frequently reaches PAST 50 than PAST 75 as evidenced by a recent open trial in which 63% of patients achieved PASI 50 versus 26% achieving PAST 75; (3) improvement in QoL exists at PAST 50, using the Dermatology Quality of Life Index, as documented in several recently completed large clinical trials; (4) patients achieving PAST 75 frequently defer therapy until they are well below PAST 50; a clinical trial where retreatment was patient initiated showed patients did not re-treat until their PAST dropped to an average of 20% improvement from baseline; and (5) effective, meaningful therapies are consistently differentiated from placebo at PAST 50 as evidenced by histologic and photographic parameters of clinical trials of alefacept, efalizumah, and etanercept. We conclude that PAST 50 equates to a clinically meaningful improvement in psoriasis and represents a discerning primary endpoint.