This was a multicenter, open-label, single-arm, phase 4 estimation study in patients with moderate-to-severe plaque psoriasis who did not have adequate response to apremilast. The study design has been described previously.4 Briefly, patients received etanercept 50 mg subcutaneously (SC) twice weekly for 12 weeks, followed by etanercept 50 mg SC once weekly for an additional 12 weeks. A copy of the protocol proposed informed consent form, other written patient information, and any proposed advertising material were submitted to the Institutional Review Board/Independent Ethics Committee at each center for written approval; all patients provided informed consent before the study.
Patients were enrolled in the study if they were at least 18 years of age; had moderate to severe plaque psoriasis (with involved body surface area [BSA] ≥10%, PASI ≥10, and static Physician Global Assessment (sPGA) ≥3 at screening and baseline); and had failed therapy with apremilast for moderate to severe plaque psoriasis, defined as, in the opinion of the investigator, either (1) failure to achieve adequate clinical response, (2) loss of adequate clinical response, or (3) intolerability to apremilast. At least 10 and no more than 20 patients could be enrolled for intolerability. In addition, patients were either currently receiving apremilast or had discontinued apremilast within 3 months before screening and had received at least 4 weeks of apremilast therapy (in patients who qualified by efficacy failure). Patients also were negative for hepatitis B and C, had no known history of tuberculosis, had a negative test for tuberculosis at screening, and had a negative serum pregnancy test ≤4 weeks before etanercept treatment.
Exclusion criteria have been described previously.4 Briefly, patients were excluded from this study if they had active skin conditions at screening that interfered with evaluations of the treatment effect on psoriasis; active malignancy within 5 years of the first dose of etanercept; history of alcoholic hepatitis, nonalcoholic steatohepatitis, hepatitis B, hepatitis C, or immunodeficiency syndromes; active infection for which antiinfectives were indicated within 4 weeks before the first dose of etanercept; or serious infection requiring hospitalization or intravenous anti-infectives within 8 weeks before screening. Patients were excluded for the following medications: (1) UVB light, topical cyclosporine, a vitamin A or D analog, calcineurin inhibitor, or topical steroids within 2 weeks before the first dose of etanercept; (2) UVA light, oral retinoids, intravenous or oral calcineurin inhibitors, anthralin, systemic psoriasis therapy, cyclophosphamide, sulfasalazine, or methotrexate within 4 weeks before the first dose of etanercept; (3) a biologic agent for psoriasis with either no satisfactory response or a clinically significant adverse event; (4) an interleukin-12/23 inhibitor within 6 months or other biologic therapies for psoriasis within 3 months before the first dose of etanercept; or (5) a biologic agent for psoriasis after discontinuing apremilast.
The PROs that were utilized in this analysis included the PSI (total and individual items) at baseline and weeks 12 and 24, as well as over time (at baseline and weeks 1, 2, 3, 4, 8, 12, 16, 20, and 24), the DLQI responder analysis at weeks 12 and 24 and the ‘patient assessment of treatment satisfaction’ at baseline and weeks 12 and 24. The PSI is an 8-item questionnaire assessing itch, redness, scaling, burning, stinging, cracking, flaking, and pain. Each item ranges from 0 (not at all severe) to 4 (very severe), for a total score ranging from 0 to 32 (higher scores indicate more severe disease).
The PSI has a 7-day recall. The DLQI is a skin-specific, 10-item questionnaire used to evaluate health-related quality of life (HRQoL). Each question ranges in score from 0 to 3, for a total score ranging from 0 (no impact of skin disease on quality of life) to 30 (maximum impact on quality of life). DLQI responders experienced a 5-point improvement or reported a score of 0. The patient assessment of treatment satisfaction is a single item 5-point scale that ranges from “very dissatisfied” to “very satisfied” to indicate a patient’s level of satisfaction with control of psoriasis from therapy. Patient satisfaction was based on the percent of patients indicating they were “satisfied” or “very satisfied.”
PROs were evaluated based on mean percent improvement in PSI total and item scores, percent of patients who were DLQI responders, and percent of patients who reported being “very satisfied” or “satisfied” with their psoriasis treatment at weeks 12 and 24. Post-hoc analyses evaluated PRO responses according to PASI achievement categories—PASI 50, PASI 75, and PASI 90—at each respective week—12 and 24. Percent of greatest change observed from baseline (i.e., normalized to highest mean percent of improvement) in PASI and PSI was also assessed.
All efficacy and PRO endpoints were analyzed in patients who received at least one dose of etanercept during the study. Missing values were imputed using last observation carried forward method (LOCF). Summary statistics and 95% confidence intervals (CIs) were generated.