Switching treatments in haemophilia: is there a risk of inhibitor development?

Patients with haemophilia A (and their physicians) may be reluctant to switch factor VIII (FVIII) concentrates, often due to concerns about increasing the risk of inhibitors; this reluctance to switch may contribute to patients missing the clinical benefits provided by the arrival of new factor VIII products. This topic was explored at the Eleventh Zurich Haemophilia Forum. Clinical scenarios for which product switching may be cause for concern were discussed; when there is a clinical need, there are no absolute contraindications to switching, but some patients (e.g. previously untreated patients and those undergoing elective surgery) may require more careful consideration. Both patient and physician surveys indicate that the reluctance to switch, and the fear of inhibitor development, does not appear to be evidence based. The evaluation of more recent data did not support previous studies suggesting that particular products (e.g. recombinant vs. plasma-derived and full length vs. B-domain modified) may be associated with increased risk. In addition, data from three national product switches showed that switching was not associated with increased inhibitor risk, but highlighted the need for regular inhibitor testing and for a centralised, unbiased database of inhibitor incidence. To conclude, current evidence does not suggest that switching products significantly influences inhibitor development

Once-Weekly Prophylactic Treatment Versus on-Demand Treatment of Nonacog Alfa in Patients with Moderately Severe to Severe Hemophilia B

56th Annual Meeting of the American-Society-of-Hematology -- DEC 06-09, 2014 -- San Francisco, CAWOS: 000349233806027Amer Soc Hemato

Beyond patient benefit: clinical development in hemophilia

Historically in hemophilia, outcome measures have not been collected systematically. Hence, there are insufficient clearly defined, evidence-based measures that can be applied consistently across hemophilia trials. This review focuses on some key challenges to evaluating patient outcomes and performing trials identified by experts at the Fourth and Fifth Zurich Haemophilia Forums. As procedures appear inconsistent across Europe, guidelines require modification to be more appropriate and/or realistically achievable. The outcome measures utilized, and the timing of their collection, should also be standardized, and more objective measures used where feasible. Implementation of outcome measures could be refined through greater understanding of patient heterogeneity, and tailored to differentiate between hemophilia- and aging-related disease effects. Furthermore, robust outcome measures that can also inform health-economic decisions are increasingly needed. Lastly, as patient recruitment poses a challenge, the panel proposed a call for action to motivate physicians and patients to participate in clinical trials

Long-term safety and efficacy of turoctocog alfa in prophylaxis and treatment of bleeding episodes in severe haemophilia A: Final results from the guardian 2 extension trial

WOS: 000451454400001PubMed ID: 30402994Introduction Turoctocog alfa is a recombinant factor VIII (FVIII) molecule, approved for treatment and prophylaxis of bleeding in patients with haemophilia A. In the guardian 1 (adolescents/adults) and guardian 3 (children) phase 3 trials, turoctocog alfa demonstrated a favourable efficacy and safety profile. Guardian 1 or 3 completers could enrol in the guardian 2 extension. Final guardian 2 results are reported here. Aim Methods Investigate long-term safety and efficacy of turoctocog alfa administered for prophylaxis and treatment of bleeds. In this phase 3b open-label trial, previously treated males of all ages with severe haemophilia A received prophylaxis regimens of turoctocog alfa or on-demand treatment of bleeds. The primary safety endpoint was frequency of FVIII inhibitor development. Efficacy endpoints included annualized bleeding rate (ABR) during prophylaxis, haemostatic response in treatment of bleeds and number of injections required to treat bleeds. Results Conclusion Overall, 213 patients were dosed with turoctocog alfa; 207 patients received prophylaxis; 19 received on-demand treatment. No FVIII inhibitors (>= 0.6 BU) were reported. For all patients on prophylaxis, overall median ABR was 1.37 bleeds/y; success rate for treatment of bleeds was 90.2%; and 88.2% of bleeds were controlled with 1-2 injections of turoctocog alfa. For the on-demand regimen, overall median ABR was 30.44 bleeds/y; success rate for treatment of bleeds was 96.7%; and 94.9% of bleeds were controlled with 1-2 injections of turoctocog alfa. Extended use of turoctocog alfa is safe and effective for prevention and treatment of bleeding episodes in previously treated patients with haemophilia A across all ages.Novo Nordisk A/SNovo NordiskNovo Nordisk A/

Hypercoagulability in Cushing's syndrome: the role of specific haemostatic and fibrinolytic markers

OBJECTIVE: Hypercoagulability is a commonly described complication in patients with Cushing's syndrome. Recent clinical studies have indicated various abnormalities of coagulation and fibrinolysis parameters which may be related to that phenomenon. The aim of this study was to investigate the mechanisms underlying the hypercoagulable state in patients with Cushing's syndrome. ----- RESEARCH METHODS AND PROCEDURES: A wide range of serum markers involved in the processes of blood coagulation and fibrinolysis was measured in a group of 33 patients with Cushing's syndrome and 31 healthy controls. No participant was taking medication which could influence the result or had known diseases, except hypertension and diabetes, which could affect blood coagulation or fibrinolysis parameters. ----- RESULTS: Patients with Cushing's syndrome had higher levels of clotting factors II (P = 0.003), V (P < 0.001), VIII (P < 0.001), IX (P < 0.001), XI (P < 0.001) and XII (P = 0.019), protein C (P < 0.001), protein S (P < 0.001), C1-inhibitor (P < 0.001) and plasminogen activator inhibitor-1 (PAI-1) (P = 0.004). The activity of fibrinolytic markers, plasminogen (P < 0.001), antithrombin (P < 0.001) and antithrombin antigen (P = 0.001) was also increased in the patient group. ----- CONCLUSION: The study has demonstrated hypercoagulability in patients with Cushing's syndrome manifest as increased prothrombotic activity and compensatory activation of the fibrinolytic system. We propose the introduction of thromboprophylaxis in the preoperative and early postoperative periods, combined with a close follow-up in order to prevent possible thromboembolic events in patients with Cushing's syndrome