Off-Label Biologic Regimens in Psoriasis Figure 1. Summary of Systematic Review Study Selection. doi:10.1371/journal.pone.0033486.g001 significant residual disease in a area of functional or high cosmetic importance [25]. Among the 591 patients who increased etanercept dose, the major reason was that patients did not achieve PASI 75 (83%, 492/591) [25]. Leonardi et al. compared the efficacy of 50 mg BIW dosing with standard 50 mg QW dosing. Specifically, the proportion of patients on the standard 50 mg QW dosing achieving PASI 75 were 44% at baseline, 61% at week 12, 65% at week 24, 68% at week 48, and 60% at week 72. In comparison, the proportion of patients on 50 mg BIW dose of etanercept achieving PASI 75 were 27% at baseline, 33% at week 12, 26% at week 24, 44% at week 48, and 43% at week 72 [25]. The proportion of patients on standard 50 mg QW etanercept achieving PGA of ‘‘clear’’ or ‘‘‘almost clear’’ was 55%, 54%, and 51% at weeks 12, 48, and 72, respectively. In comparison, the proportion of those on 50 mg BIW dosing achieving ‘‘clear’’ or ‘‘almost clear’’ was 26%, 28%, and 27% at weeks 12, 48, and 72, respectively [25]. Efficacy of Etanercept Dose Reduction. A search of the literature identified two studies that investigated dose reduction with etanercept [16,26]. Leonardi et al. compared 25 mg QW etanercept and 25 mg BIW etanercept to standard induction dosing of 50 mg BIW for 24 weeks [16]. At week 12, 14% of patients receiving 25 mg QW therapy and 34% of those receiving 25 mg BIW therapy achieved PASI 75 compared to 49% of patients on the standard induction dose. Similarly, at week 24, 25% of patients receiving 25 mg QW and 44% of those receiving 25 mg BIW achieved PASI 75 compared to 59% of those receiving 50 mg BIW etanercept [16]. Cassano et al. compared 24 weeks of 50 mg QW therapy to standard induction and maintenance dose etanercept [26]. At week 12, PASI 50 was achieved by 75% of patients receiving 50 mg QW induction therapy compared to 92% of patients on 50 mg BIW induction therapy (p = 0.06). Those who achieved PASI 50 at week 12 on etanercept 50 mg QW were continued on the same dose for another 12 weeks. At week 24, PASI 50 was achieved by 100% of those who were continued at 50 mg QW and 100% of those who received standard 50 mg BIW induction therapy followed by 50 mg QW maintenance etanercept [26]. Efficacy of Etanercept Withdrawal and Retreatment. After reviewing the literature, three studies that investigated etanercept withdrawal and retreatment were included in this article [27–29]. Gordon et al. studied a withdrawal period followed by 24 weeks of retreatment with a randomized dose of 50 mg BIW etanercept, 25 mg BIW etanercept, or 25 mg QW etanercept [27]. The median time to disease relapse was reported to be 85 days, which is defined as the time period during which at least half of the numerical improvement in PASI that occurred in the initial 24-week treatment and follow-up period was lost. The investigators reported that the median time to loss of PASI 75 for patients who achieved PASI 75 during the 24-week treatment cycle was 57 days [27]. Retreatment efficacy, defined as the PLoS ONE | www.plosone.org 3 April 2012 | Volume 7 | Issue 4 | e33486