Title: The efficacy and safety of etanercept in the re-treatment of psoriasis after relapse
Abstract: Introduction: Dermatologists often use an intermittent and/or rotational paradigm when treating psoriasis, but the safety and efficacy profiles of etanercept therapy when re-treating psoriasis after drug withdrawal is unknown. Methods: This phase 3 trial of etanercept in psoriasis was designed with a 24-week double-blind period followed by a study drug withdrawal and re-treatment period. During the 24-week double blind period, patients were randomized to receive either etanercept (50 mg twice weekly [BIW], 25 mg BIW, or 25 mg once weekly [QW]) or placebo BIW. Patients randomized to the placebo group began etanercept (25 mg BIW) at week 12 in a blinded fashion. At week 24, those patients classified as responders (had ≥50% decrease from baseline PASI) were discontinued from study drug and followed until their disease relapsed (loss of ≥50% of PASI improvement obtained between baseline and week 24), at which time patients resumed blinded etanercept therapy for up to 24 weeks. This interim analysis focuses on the efficacy and safety of etanercept therapy during this re-treatment period. Results: Of 652 patients initiating this trial, 573 (87.9%) completed 24 weeks of treatment. Of these completers, 409 (71.4%) achieved a PASI 50 response at week 24 (responders) and entered the study drug withdrawal and re-treatment period. As of the interim data cut-off date, 113 patients (of 277 relapsed patients) had completed 12 weeks of re-treatment following relapse. Comparison of PASI scores between week 12 of initial active treatment (mean PASI score of 6.7) and week 12 of re-treatment (mean PASI score of 7.6) revealed that the overall effect of re-treatment with etanercept was similar to the initial treatment effect (95% confidence interval of the mean differences in PASI scores for all doses either contain or are close to zero). Moreover, 45 of the 113 patients re-treated for at least 12 weeks (39.8%) had PASI scores that were improved over their initial 12-week treatment period. The rates of adverse events, infections, and antigenicity in the 12-week re-treatment period were lower than or similar to the first 12 weeks of initial active treatment. During the retreatment period, anti-etanercept antibodies were rare (2%) and non-neutralizing, and no patient had a rebound of more than 125% of the baseline PASI score. Conclusions: These data suggest the potential for etanercept to be used safely and effectively in an intermittent or rotational paradigm in the treatment of psoriasis. Craig Leonardi is on the Advisory Board and Speaker’s Bureau for Amgen. Boni Elewski has done clinical research for Amgen, and also has served as a consultant. Charles Camisa has no conflict of interest. Ralph Zitnik is an employee of Amgen.