Etanercept in pediatric patients was generally well tolerated and efficacy was maintained in those who remained in the study for up to 264 weeks.

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Background OBSERVE-5 was a 5-year FDA-mandated surveillance registry of psoriasis patients. Objective To assess long-term etanercept safety and effectiveness. Methods Patients with moderate to severe psoriasis enrolled; a single baseline dose of etanercept was required. Key outcome measures included serious adverse events (SAEs), serious infectious events (SIEs), events of medical interest, psoriasis-affected body surface area, physician global assessment, and Dermatology Life Quality Index. Safety outcomes were assessed relative to data from the MarketScan database. Results For 2,510 patients, 5-year cumulative incidence (95% confidence interval [CI]) was 22.2% (20.3%, 24.2%) for SAEs; 6.5% (5.4%, 7.7%) for SIEs; 3.2% (2.3%, 4.1%) for malignancies excluding nonmelanoma skin cancer (NMSC); 3.6% (2.7%, 4.5%) for NMSC; 2.8% (2.0%, 3.6%) for coronary artery disease; 0.7% (0.3%, 1.2%) for psoriasis worsening; 0.2% (0.0%, 0.4%) for CNS demyelinating disorder; 0.1% (0.0%, 0.3%) for lymphoma and for tuberculosis; 0.1% (0.0%, 0.2%) for opportunistic infection and for lupus; 55 fatal events were reported. Rates of malignancies, lymphomas, NMSC, and hospitalization-associated infections were not higher than expected relative to administrative claims data. The percentage of patients rated as clear/almost clear was 12% at baseline, which increased to 51% at month 6 and remained relatively stable throughout 5 years. Limitations No internal comparator group was included; rare events may not have been detected. Conclusion No new safety signals were observed with long-term, real-world etanercept use.

Efanesoctocog alfa (rFVIIIFc-VWF-XTEN, BIVV001) is a new class of factor VIII (FVIII) replacement that breaks the von Willebrand factor-imposed FVIII half-life ceiling. In a Phase 1/2a study, single-dose efanesoctocog alfa was well tolerated and no safety concerns were identified. We evaluated the safety, tolerability, and pharmacokinetics of repeat-dose efanesoctocog alfa in a Phase 1 study in previously treated adults (≥150 exposure days) with severe hemophilia A. Participants received four once-weekly efanesoctocog alfa doses (Cohort 1, 50 IU/kg; Cohort 2, 65 IU/kg). All enrolled participants (Cohort 1, n=10; Cohort 2, n=14) completed the study. Inhibitor development to FVIII was not detected. After the last efanesoctocog alfa dose, geometric mean (range) FVIII activity half-life, area under the activity-time curve, and steady state maximum concentration for Cohort 1 and Cohort 2 were 41.3 (34.2-50.1) hours and 37.3 (28.9-43.8) hours, 8290 (5810-10,300) h × IU/dL and 11,200 (7040-15,800) h × IU/dL, and 131 (96-191) IU/dL and 171 (118-211) IU/dL, respectively. There was minimal accumulation after 4 doses. Mean FVIII activity on Day 3 post dose was 46% and 69% and on Day 7 was 10% and 12% for Cohorts 1 and 2, respectively. Overall, four once-weekly doses of efanesoctocog alfa were well tolerated, no safety concerns identified, and no bleeds reported during the treatment period. Once-weekly efanesoctocog alfa provided high sustained FVIII activity within the normal to near-normal range for 3-4 days post-dose and may improve protection against bleeds in patients with hemophilia A. (EU Clinical Trials Register study 2018-001535-51)

SummaryBackground Some patients with plaque psoriasis experience secondary failure of tumour necrosis factor inhibitor therapy. Objectives To evaluate efficacy, safety and patient-reported outcomes (PROs) with etanercept in patients with secondary adalimumab failure. Methods This phase IV open-label single-arm estimation study (NCT01543204) enrolled patients on adalimumab who had achieved static Physician's Global Assessment (sPGA) score 0/1 (clear/almost clear). Patients subsequently lost response, defined as sPGA ≥ 3 or loss of 50% improvement in Psoriasis Area and Severity Index (PASI 50). At baseline, patients had involved body surface area ≥ 10%, sPGA ≥ 3 and PASI ≥ 10. Antiadalimumab antibodies (ADAs) were measured at screening. Patients received etanercept 50 mg twice weekly for 12 weeks, followed by 50 mg weekly. The primary end point was sPGA 0/1 at week 12 (intention-to-treat analysis; no hypothesis tested). Additional outcomes included rates of sPGA 0/1, PASI responses, safety, PROs of itch, pain and flaking, Dermatology Life Quality Index, treatment satisfaction and Work Productivity and Activity Impairment questionnaire. Results Sixty-four patients enrolled; 67% had ADAs. sPGA 0/1 rates at week 12 were 39Á7% [95% confidence interval (CI) 27Á6-52Á8; primary end point] and 45% (95% CI 29Á3-61Á5) for patients positive for ADAs and 35% (95% CI 15Á4-59Á2) for patients negative for ADAs. PASI 75 response rates at week 12 were 47Á5% (95% CI 31Á5-63Á9) for patients who were positive for ADAs and 50% (95% CI 27Á2-72Á8) for patients negative for ADAs. No new safety signals were observed. PROs of itch, pain and flaking consistently improved at week 12 and were maintained through week 24. Conclusions Patients with psoriasis who experienced secondary failure of adalimumab achieved satisfactory response to etanercept regardless of ADA status.