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 vs. on-demand treatment with nonacog alfa in patients with moderately severe to severe haemophilia B

WOS: 000379715000034PubMed ID: 26823276Introduction: Limited data are available on optimal prophylaxis regimens of factor IX (FIX) replacements for patients with haemophilia B. Aim: This multicentre, open-label study evaluated the efficacy and safety of once-weekly prophylaxis with nonacog alfa compared with on-demand treatment in adolescent and adult patients. Methods: Males aged 12-65 years with moderately severe to severe haemophilia B (FIX:C 2 IU dL(-1) (min-max of 2.13-10.39 IU dL(-1)). Conclusions: Once-weekly prophylaxis of 100 IU kg(-1) was associated with lower ABR compared with on-demand treatment in adolescents and adults with moderately severe to severe haemophilia B. Once-weekly prophylaxis was well tolerated, with a similar safety profile as that reported during the on-demand treatment period. Residual FIX: C may be supportive of effectiveness

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