OBSERVE-5 interim analysis: an observational postmarketing safety registry of etanercept for the treatment of psoriasis.

BACKGROUND: Etanercept is approved for the treatment of chronic moderate to severe plaque psoriasis in adults. OBJECTIVE: We sought to evaluate the long-term safety of etanercept in a real-world clinical setting. Assessment of etanercept efficacy was a secondary objective. METHODS: OBSERVE-5 is a 5-year observational safety registry initiated in May 2006 at multiple sites in the United States and Canada. Data collection includes the number of serious adverse events, serious infectious events, and prespecified events of medical interest. Efficacy data include body surface area assessments, physician and patient global assessments of psoriasis, and the Dermatology Life Quality Index. This interim analysis presents data from the first 3 years of the follow-up period. RESULTS: A total of 2511 patients were enrolled. Of 1890 patients continuing in the registry after 3 years, 113 were inactive for 1 to 2 years, and 115 were inactive for longer than 2 years. The 3-year incidence proportions of serious adverse events and serious infectious events based on Kaplan-Meier methodology were 0.14 and 0.04, respectively. The observed numbers of patients experiencing lymphoma, serious infectious events requiring hospitalization, nonmelanoma skin cancer, and malignancies excluding nonmelanoma skin cancer were not higher than the expected number of cases estimated from a large US administrative health claims database. LIMITATIONS: The registry lacks a control group, and the study is too small to measure the frequency of rare events. CONCLUSION: Etanercept demonstrated good tolerability in patients with plaque psoriasis in the clinical setting in this interim analysis. No new or unexpected safety concerns were observed.

Patient-reported outcomes in pediatric patients with psoriasis undergoing etanercept treatment: 12-week results from a phase III randomized controlled trial.

BACKGROUND: Psoriasis adversely affects health-related quality of life (HRQoL) in adults; however, little information exists about its impact on children and adolescents. OBJECTIVE: The effect of etanercept therapy on HRQoL compared with placebo was evaluated in children and adolescents with moderate to severe plaque psoriasis. METHODS: HRQoL data were collected from patients 4 to 17 years of age in a randomized, double-blind, placebo-controlled, North American, phase III study of etanercept. Instruments for assessing HRQoL included the Children's Dermatology Life Quality Index (CDLQI), Pediatric Quality of Life Inventory (PedsQL), Stein Impact on Family Scale, and Harter Self-Perception Profile for Children. RESULTS: Baseline CDLQI and PedsQL scores revealed reduced HRQoL in patients with psoriasis relative to comparative populations. Patients treated with etanercept demonstrated significantly higher mean percentage improvement in total CDLQI scores from baseline to week 12 compared with those treated with placebo (52.3% etanercept vs 17.5% placebo [P = .0001]). At week 12, patients who achieved 75% improvement in their Psoriasis Area and Severity Index score had higher percentage improvements from baseline in total CDLQI scores than those who did not have 75% improvement in Psoriasis Area and Severity Index score. LIMITATIONS: The PedsQL, Stein scale, and Harter profile demonstrated limited improvement in patients' HRQoL, suggesting that these scales may not be sensitive to issues that are relevant to children with psoriasis and their families. CONCLUSION: Etanercept therapy had a clinically and statistically meaningful impact on disease-specific quality of life (CDLQI) and a clinically meaningful impact on general quality of life (PedsQL) in children and adolescents with moderate to severe plaque psoriasis.

Intermittent etanercept therapy in pediatric patients with psoriasis.

BACKGROUND: Stopping and restarting etanercept is well tolerated in adult psoriasis, but little is known about intermittent use in pediatric psoriasis. OBJECTIVE: We sought to assess safety and efficacy of etanercept administered intermittently in children with psoriasis. METHODS: At study entry, patients were 4 to 17 years old with moderate to severe stable plaque psoriasis (Psoriasis Area and Severity Index [PASI] score ≥ 12). After an initial 12-week, double-blind period and a 24-week, open-label period, eligible patients (ie, achieved 75% improvement in PASI response from baseline [PASI 75]) were re-randomized to a 12-week, double-blind withdrawal-retreatment period: patients received placebo (withdrawal) or etanercept as long as they maintained PASI 75; otherwise, they were retreated with open-label etanercept (retreatment). RESULTS: The 138 patients who entered the withdrawal-retreatment period were re-randomized equally between placebo and etanercept. In the group treated with blinded or open-label etanercept, 52 of 65 (80%; observed data) patients maintained or regained PASI 75 at the end of the 12-week period. In all, 45 of 64 (70%) patients on blinded etanercept maintained PASI 75 at every study visit during the 12-week period, compared with 35 of 65 (54%) patients who did so on blinded placebo. No patient had a serious adverse event, serious infection, or withdrew from study because of an adverse event. LIMITATIONS: Small study and short observation period are limitations. CONCLUSION: During the final 12-week withdrawal-retreatment period of this 48-week study, intermittent etanercept therapy appeared safe, with no patients experiencing a serious adverse event or serious infection, and effective, with 80% of patients on etanercept maintaining or regaining PASI 75 at the end of the 12-week period.

Long-term etanercept in pediatric patients with plaque psoriasis.

BACKGROUND: No systemic therapies are approved by the US Food and Drug Administration for the treatment of psoriasis in children and adolescents. OBJECTIVE: We sought to evaluate the long-term safety and efficacy of etanercept in pediatric patients (aged 4-17 years) with moderate to severe plaque psoriasis. METHODS: Patients who completed or received substantial treatment benefit in a 48-week, randomized, double-blind, placebo-controlled study (N = 211) evaluating the efficacy and safety of once-weekly etanercept (0.8 mg/kg) were enrolled in this 264-week open-label extension study. The primary end point was the occurrence of adverse events. Secondary end points included Psoriasis Area and Severity Index 50%, 75%, and 90% responses compared with baseline; static Physician Global Assessment; and clear and clear/almost clear static Physician Global Assessment status. Results from a 96-week interim analysis are presented. RESULTS: Of 182 enrolled patients, 181 received treatment and 140 (76.9%) completed week 96. A total of 145 patients (80.1%) reported adverse events; 5 serious adverse events occurred in 3 patients, none of which were treatment related. Observed Psoriasis Area and Severity Index 50% (89%), 75% (61%), and 90% (30%) responses compared with baseline at week 96 were similar to those observed in the double-blind trial. The static Physician Global Assessment was maintained through week 96, when 47% of patients achieved clear/almost clear status. LIMITATIONS: This is an interim analysis from an open-label study. CONCLUSION: Extended treatment with etanercept in pediatric patients with moderate to severe plaque psoriasis was generally well tolerated, and efficacy was maintained through 96 weeks.

Etanercept treatment for children and adolescents with plaque psoriasis.

BACKGROUND: Etanercept, a soluble tumor necrosis factor receptor, has been shown to lessen disease severity in adult patients with psoriasis. We assessed the efficacy and safety of etanercept in children and adolescents with moderate-to-severe plaque psoriasis. METHODS: In this 48-week study, 211 patients with psoriasis (4 to 17 years of age) were initially randomly assigned to a double-blind trial of 12 once-weekly subcutaneous injections of placebo or 0.8 mg of etanercept per kilogram of body weight (to a maximum of 50 mg), followed by 24 weeks of once-weekly open-label etanercept. At week 36, 138 patients underwent a second randomization to placebo or etanercept to investigate the effects of withdrawal and retreatment. The primary end point was 75% or greater improvement from baseline in the psoriasis area-and-severity index (PASI 75) at week 12. Secondary end points included PASI 50, PASI 90, physician's global assessment of clear or almost clear of disease, and safety assessments. RESULTS: At week 12, 57% of patients receiving etanercept achieved PASI 75, as compared with 11% of those receiving placebo (P<0.001). A significantly higher proportion of patients in the etanercept group than in the placebo group had PASI 50 (75% vs. 23%), PASI 90 (27% vs. 7%), and a physician's global assessment of clear or almost clear (53% vs. 13%) at week 12 (P<0.001). At week 36, after 24 weeks of open-label etanercept, rates of PASI 75 were 68% and 65% for patients initially assigned to etanercept and placebo, respectively. During the withdrawal period from week 36 to week 48, response was lost by 29 of 69 patients (42%) assigned to placebo at the second randomization. Four serious adverse events (including three infections) occurred in three patients during treatment with open-label etanercept; all resolved without sequelae. CONCLUSIONS: Etanercept significantly reduced disease severity in children and adolescents with moderate-to-severe plaque psoriasis. (ClinicalTrials.gov number, NCT00078819 [ClinicalTrials.gov].).