Efficacy, safety and pharmacokinetics of recombinant human coagulation factor VIII (omfiloctocog alfa) in previously treated Chinese children with severe hemophilia A.

INTRODUCTION: Omfiloctocog alfa, the first China-developed recombinant factor VIII (FVIII), demonstrated efficacy and safety of prophylaxis in previously treated patients (PTPs) aged ≥12 years with severe hemophilia A in China. AIMS: To investigate efficacy, safety and pharmacokinetics (PK) of omfiloctocog alfa in pediatric PTPs with severe hemophilia A in China. METHODS: PTPs (>50 exposure days [ED] for Chinese patients aged <6 years; >150 EDs for patients aged 6-12 years) were treated with omfiloctocog alfa at 25-50 IU/kg every other day or three times per week for 24 weeks. PK was evaluated after single injection of 50 IU/kg. The primary efficacy endpoint was annualized bleeding rate (ABR). RESULTS: A total of 69 patients were enrolled (<6 years, n = 35; 6-12 years, n = 34) and mean exposure to omfiloctocog alfa was 78.9 days. Mean half-life was 6.7 and 10.2 h in children < 6 years and 6-12 years, respectively. Estimated mean ABRs of all patients were 4.05 for overall bleeding episodes and 1.38 for spontaneous bleeding episodes. Of 127 bleeding episodes, the success rate was 92.1%. 39.7% patients did not experience any bleeding episodes and the mean weekly dose of FVIII was 109.1 IU/kg for these patients. 83% bleeding episodes were controlled with ≤2 injections. Adverse reactions occurred in 2.9% of the patients. One 2-year-old patient developed inhibitors after 12 EDs and it resolved with omfiloctocog alfa immune tolerance induction. CONCLUSION: Omfiloctocog alfa was efficacious and well tolerated for the prevention and treatment of bleeding in Chinese pediatric PTPs with severe hemophilia A.

[Effects of bosentan in treatment of pulmonary arterial hypertension: a pilot study of 21 patients].

OBJECTIVE: To investigate the preliminary efficacy and safety of bosentan, a dual endothelin-receptor antagonist, in Chinese pulmonary arterial hypertension (PAH) patients. METHODS: 21 patients with PAH, idiopathic or associated with congenital heart disease or connective-tissue disease received 62.5 mg of bosentan twice daily for 4 weeks, and then 125 mg twice daily for 8 weeks if without serious side effects. At week 12, the patients underwent 6 min walk test, hemodynamic variables examination, right heart catheterization, ultrasound cardiography, and electrocardiography. RESULTS: The six-minute walking distance 12 weeks after bosentan treatment was 461 m +/- 84 m, significantly longer than that before the therapy (374 m +/- 113 m, P < 0.001). The pulmonary vascular resistance 12 weeks after the bosentan treatment was (1236 +/- 729) dyn x s(-1) x cm(-5), significantly lower than that before [(1,440 +/- 766) dyn x s(-1) x cm(-5), P = 0.007]. The cardiac index 12 weeks after the bosentan treatment was (3.02 +/- 1.71) L x min(-1)xm(2), significantly higher than that before treatment [(2.35 +/- 1.20) L x min(-1)xm(2), P = 0.002]. No patient was withdrawn from this study for safety reason. CONCLUSION: Improves the exercise capacity and hemodynamic parameters in Chinese PAH patients; bosentan is safe in treating PAH and can be well tolerated.

Hemodynamic variables and clinical features correlated with serum uric acid in patients with pulmonary arterial hypertension.

BACKGROUND: Serum uric acid (UA), the final product of purine degradation, has been proposed to be a marker for the severity and a possible predictor of mortality in patients with pulmonary arterial hypertension (PAH). The objectives of this study were to elucidate whether serum UA level correlates with the clinical features and the hemodynamic variables in Chinese patients with PAH and to compare the difference of the correlates in patients associated with different etiologies. METHODS: Serum UA was assessed in 228 patients with three types of PAH (idiopathic PAH (IPAH), congenital heart disease related PAH (CHD-PAH) and connective tissue disease related PAH (CTD-PAH)) together with other clinical features. After the individualized treatment for at least 6 months, the UA levels and clinical features were re-evaluated in 88 patients. RESULTS: Serum UA was significantly elevated in patients with PAH compared with age-matched control subjects ((350.40 +/- 108.73) micromol/L vs (266.91 +/- 81.38) micromol/L), P < 0.001). Serum UA negatively correlated with cardiac output and mixed venous saturation (SvO(2)) in all three types of PAH (all P < 0.05), positively correlated with the size of right ventricle in IPAH (P = 0.002) and CTD-PAH (P = 0.013) patients and with pulmonary vascular resistance just in CTD-PAH patients (P = 0.001). Serum UA significantly decreased from (365.80 +/- 120.46) micromol/L to (333.67 +/- 117.56) micromol/L in 88 patients (P = 0.006) with vasodilator therapy for at least 6 months, accompanied with a reduction in pulmonary vascular resistance from (15.13 +/- 6.96) Woods unit to (12.00 +/- 5.04) Woods unit (P = 0.001) and an increase in cardiac output from (2.63 +/- 0.98) L/min to (3.08 +/- 1.04) L/min (P = 0.005). CONCLUSIONS: Serum UA increases in proportion to the clinical severity of all the three types of PAH, especially the CTD-PAH had a stronger correlations compared with IPAH and CHD-PAH. The serum UA levels also could partly reflect the response to the treatment in patients with PAH.