OBJECTIVES: This analysis evaluated whether the Dermatology Life Quality Index (DLQI) and the Psoriasis Area and Severity Index (PASI) have different responsiveness to measure change of treatment effect in moderate to severe psoriasis patients. METHODS: In PHOENIX I, 766 patients were randomized to ustekinumab 45 mg or 90 mg at weeks 0 and 4 and then q12 weeks thereafter, or placebo at weeks 0 and 4 with crossover to ustekinumab at week 12. Ustekinumab-randomized patients achieving PASI75 response at weeks 28 and 40 were re-randomized at week 40 to continue maintenance ustekinumab or be withdrawn from treatment until loss of response. DLQI and PASI were assessed at weeks 0, 2, 12, 28, 40 and 52. Multiple regression models were used to assess treatment effect on DLQI by adjusting for PASI improvement. RESULTS: Significantly greater proportions of patients receiving ustekinumab achieved PASI75 response (66.7%) and clinically meaningful improvement (≥5 points) in DLQI (67.8%) compared with placebo (3.1% and 6.0%, each p<0.001) at week 12. There was a significant correlation between the change in DLQI and change in PASI (r=0.65, p<0.001). After adjustment for baseline DLQI, baseline PASI, and change in PASI, ustekinumab was still associated with significant improvement in DLQI (p<0.001). For patients originally randomized to ustekinumab, the median % improvement from baseline was higher in DLQI (37.5%) than in PASI (21.4%) at week 2, with 11.4% of patients achieving a DLQI score of ≤1, but only 1% achieving a PASI75 response.  At week 28 and 40, the DLQI and PASI achieved and maintained similar improvements of ≥90% from baseline. For those who achieved and maintained a PASI75 response from week 12 through week 40, but lost response at week 52, the median improvement in DLQI decreased more significantly (100% at week 40 to 46% at week 52, a 54% reduction) than PASI that decreased from 88.9% at week 40 to 57.6% at week 52 (35.0% reduction). CONCLUSIONS: The DLQI may be more responsive to change of disease status due to treatment intervention than PASI.