Safety and Efficacy of Turoctocog Alfa in the Prevention and Treatment of Bleeding Episodes in Previously Treated Patients from China with Severe Hemophilia A: Results from the Guardian 7 Trial.

PURPOSE: Hemophilia care in China is characterized by widespread use of on-demand regimens and low-dose prophylaxis. With a limited number of approved recombinant factor VIII (FVIII) products, the incidence of arthropathy and disability in hemophilia patients remains high in China. The purpose of this trial was to evaluate the safety and efficacy of turoctocog alfa for prophylaxis and treatment of bleeding episodes in patients from China with severe hemophilia A across all age groups. PATIENTS AND METHODS: In this Phase 3, open-label trial, previously treated males of all ages with severe hemophilia A from China received turoctocog alfa for prophylaxis or on-demand treatment of bleeds. The primary endpoint was hemostatic effect for the treatment of bleeds during the main phase of the trial. Secondary endpoints included annualized bleeding rate during prophylaxis and the frequency of FVIII inhibitor development. RESULTS: Overall, 42 pediatric patients (age <12 years) and 26 adolescent/adult patients (≥12 years) were dosed with turoctocog alfa; 51 patients initiated treatment with prophylaxis, while 17 patients initiated on-demand treatment. During the main phase of the trial (6 months), hemostatic success was 95.1%. During the full trial (up to 24 months), hemostatic success was 95.4%; the overall median ABR was 1.18 bleeds/patient/year for prophylaxis patients; and 25 (51.0%) of 49 patients with target joints at baseline had all target joints resolved. No FVIII inhibitors (≥0.6 BU) were reported. CONCLUSION: Turoctocog alfa was safe and effective for prophylaxis and treatment of bleeding episodes and for surgery in patients from China with severe hemophilia A across all ages.

A case report of acute inferior myocardial infarction in a patient with severe hemophilia A after recombinant factor VIII infusion.

RATIONALE: The extent of protective effects of hemophilia against thrombotic events such as myocardial infarction (MI) and other acute coronary syndromes remains to be determined, as major risk factors for cardiovascular disease exist despite factor VIII (FVIII) deficiency. We present a case report of a 41-year-old male with severe hemophilia A and several cardiovascular risk factors. PATIENT CONCERNS: This morbidly obese patient developed chest pressure, followed by chest pain and difficulty in breathing shortly after receiving on-demand treatment with intravenous recombinant FVIII (rFVIII) (turoctocog alfa) dosed per body weight. DIAGNOSES: An electrocardiogram revealed a diagnosis of inferior ST-segment elevation MI. INTERVENTIONS: The patient underwent an urgent coronary angiography using a radial artery approach. During the next 12 months, he received dual antiplatelet treatment, acetylsalicylic acid 100 mg, and clopidogrel 75 mg daily. His treatment for severe hemophilia A was changed to plasma-derived FVIII replacement therapy. OUTCOMES: During this 12-month period, he experienced several small bleeds in his elbows. CONCLUSIONS: The temporal relationship between rFVIII infusion and onset of the MI suggests a possible association; however, apart from obesity, the patient also had other major risk factors for arterial thrombosis, such as hypertension and smoking. Furthermore, atherosclerotic disease and underlying atherosclerotic changes could not be excluded with certainty. This case highlights the importance of studies assessing the impact of excess body weight on rFVIII dosing.

Mental health and alcohol, drugs and tobacco: a review of the comorbidity between mental disorders and the use of alcohol, tobacco and illicit drugs.

This paper reviews some major epidemiological studies undertaken in high-income countries during the last 15 years which have reported the prevalence of mental disorders and substance use disorders and their relationship. Comorbidity between mental and substance use disorders is highly prevalent across countries. In general, people with a substance use disorder had higher comorbid rates of mental disorders than vice versa, and people with illicit drug disorders had the highest rates of comorbid mental disorders. There is a strong direct association between the magnitude of comorbidity and the severity of substance use disorders. While causal pathways differ across substances and disorders, there is evidence that alcohol is a casual factor for depression, in some European countries up to 10% of male depression. Policies that reduce the use of substances are likely to reduce the prevalence of mental disorders. Treatment should be available in an integrated fashion for both mental and substance use disorders. There is a need to expand the evidence base on comorbidity, particularly in low-income countries.