Recombinant long-acting glycoPEGylated factor IX in hemophilia B: a multinational randomized phase 3 trial.

This multinational, randomized, single-blind trial investigated the safety and efficacy of nonacog beta pegol, a recombinant glycoPEGylated factor IX (FIX) with extended half-life, in 74 previously treated patients with hemophilia B (FIX activity ≤2 IU/dL). Patients received prophylaxis for 52 weeks, randomized to either 10 IU/kg or 40 IU/kg once weekly or to on-demand treatment of 28 weeks. No patients developed inhibitors, and no safety concerns were identified. Three hundred forty-five bleeding episodes were treated, with an estimated success rate of 92.2%. The median annualized bleeding rates (ABRs) were 1.04 in the 40 IU/kg prophylaxis group, 2.93 in the 10 IU/kg prophylaxis group, and 15.58 in the on-demand treatment group. In the 40 IU/kg group, 10 (66.7%) of 15 patients experienced no bleeding episodes into target joints compared with 1 (7.7%) of 13 patients in the 10 IU/kg group. Health-related quality of life (HR-QoL) assessed with the EuroQoL-5 Dimensions visual analog scale score improved from a median of 75 to 90 in the 40 IU/kg prophylaxis group. Nonacog beta pegol was well tolerated and efficacious for the treatment of bleeding episodes and was associated with low ABRs in patients receiving prophylaxis. Once-weekly prophylaxis with 40 IU/kg resolved target joint bleeds in 66.7% of the affected patients and improved HR-QoL. This trial was registered at www.clinicaltrials.gov as #NCT01333111.

Quality of life after severe trauma: results from the global trauma trial with recombinant Factor VII.

BACKGROUND: Physical disability and psychologic morbidity are frequent and important complications of severe trauma injury with serious consequences for long-term health-related quality of life (HRQOL). Little prospective data exist, however, in a global trauma population on the risk factors for poor HRQOL. METHODS: The CONTROL trial was a prospective, randomized, double-blinded, multicenter, placebo-controlled trial conducted from August 2005 to September 2008. HRQOL was assessed 3 months after injury using the Polytrauma Outcome Chart (Glasgow Outcomes Scale, Short Form 36, European Quality of Life-5 Dimensions (EQ-5D), and Trauma Outcome Profile). Multivariate stepwise regression analysis identified predictors of poor HRQOL. RESULTS: Three hundred forty-seven (72%) patients completed at least one HRQOL instrument. Three percent had an EQ-5D score <0 (worse than death); 92% had a score <0.87 (average score in the general population). All HRQOL instruments identified physical functioning and activities of daily living as the dimensions of health most significantly affected by trauma injury. Mental functioning was also significantly affected according to the Trauma Outcome Profile. Independent predictors of poor HRQOL were higher age, female gender, extremity injury, blunt injury, intensive care unit stay >3 days, repeated nonadherence to transfusion guidelines, and inability to work postinjury. CONCLUSIONS: Three months after severe trauma injury, survivors report very poor HRQOL. Physical wellbeing is generally more negatively affected than mental wellbeing. A trauma-specific HRQOL instrument reveals more diverse mental health problems than generic instruments. In a global trauma population, postinjury HRQOL is predicted by demographic and socioeconomic characteristics, type of injury, and treatment received.