Optimising immune tolerance induction strategies in the management of haemophilia patients with inhibitors: a cost-minimisation analysis

ABSTRACT

Background: The objective of this study was to model the economic impact of optimal dosing of immune tolerance induction (ITI) in haemophilia patients with inhibitors. Evidence based research suggests that, in the right patient population characterised by ITI risk status, the use of high-dose ITI regimen in ‘poor risk’ patients, and the low-dose regimen in ‘good risk’ patients, would be the cost effective strategy. The model also explored the impact of anamnestic response (AR), a phenomenon which worsens patients’ ITI risks.

Method: A cost-minimisation technique was used to compare the cost of managing inhibitor patients whose bleeds were managed pre-ITI with an immunogenic bypassing agent, activated prothrombin complex concentrate (APCC), with patients previously on a non-immunogenic product, recombinant activated factor VII (rFVIIa). Patients were subsequently offered a low-dose or high-dose ITI regime depending on their ITI risk status. The study perspective was that of the United Kingdom NHS, hence, all resources used were based on UK costs.

Results: The model estimated the mean cost of managing inhibitor patients from detection of titres through ITI to be £959 250.39 and £770 834.17 in the APCC and rFVIIa treatment options, respectively. Meanwhile, the costs per effectively tolerised patients were £1 505 279 and £1 196 706 for APCC and rFVIIa treated patients, respectively. Of the incremental cost in the APCC-treated patients in the model, £129 367 (68%) represents additional ITI cost attributable to anamnestic response to earlier treatment with an immunogenic bypassing agent (APCC).

Conclusion: The study concludes that decreasing factor VIII usage during ITI, through the identification and management of ‘good risk’ ITI patients with low-dose protocol, while managing ‘poor risk’ patients with high-dose regimen, will significantly lower the cost of ITI. Furthermore, avoiding AR prior to ITI by using non-immunogenic bypassing agents to manage spontaneous bleeds also has the potential for significant cost savings.

Key words: :

• Activated prothrombin complex concentrate
• Anamnestic response
• Cost-minimisation analysis
• Haemophilia
• Recombinant activated factor VII

Acknowledgements

Declaration of interest: This study was supported by an unrestricted research grant from Novo Nordisk A/S, Bagsvaerd, Denmark. Novo Nordisk is the manufacturer of the anti-haemophilic product, activated recombinant factor VII. I.A.O.O. is a former employee of Novo Nordisk, and A.M.D. is currently employed by Novo Nordisk.