Modelling lifelong effects of different prophylactic treatment strategies for severe haemophilia A

Abstract

Background: Lifelong prophylactic replacement therapy with clotting factor concentrates is recommended for severe haemophilia. The prophylactic dose determines both clinical outcome and treatment cost. In the absence of clinical studies, computer simulation was used to explore lifelong effects and clotting factor consumption for various prophylactic dose levels, and optimize strategies for switching between prophylactic and on-demand treatment. Design and Methods: Individual patients' lifetime joint bleeds, radiological arthropathy (Pettersson score, 0-78) and consumption were simulated for each treatment strategy. Treatment effectiveness (expressed as % of patients maintaining a lifetime Pettersson score ≤14) and clotting factor consumption were modelled for lifelong prophylaxis at dose levels 1000-4500 IU kg À1 year À1, for on-demand treatment and for switching strategies. Treatment efficiency (consumption per unit of effectiveness) was used to compare strategies. Results: Compared to lifelong on-demand treatment, lifelong prophylaxis at 1000 IU kg À1 year À1 increased effectiveness from 21 to 36%, at an additional consumption of 0.9 9 10 6 IU kg À1 . For lifelong prophylaxis, each additional 1000 IU kg À1 year À1 resulted in a proportional increase in consumption by AE5 9 10 6 IU kg À1 but a less than proportional reduction in arthropathy by AE50%; consequently, increasing consumption progressively diminished treatment efficiency. Switching strategies slightly reduce effectiveness and consumption. Optimum switching criteria were similar across prophylactic dose levels. Conclusion: According to the simulation model, low-dose prophylaxis (1000 IU kg À1 year À1) improved outcome at a limited increase in consumption compared to ondemand treatment. Increasing prophylactic dose further improved health outcomes, but at decreasing efficiency. Optimal prophylactic dose should therefore be selected balancing acceptable health impact and available budget.

The association of haemophilic arthropathy with Health‐Related Quality of Life: apost hocanalysis

“…Although the direct clinical relevance of radiological joint changes is limited, its association with HRQoL is highly relevant, especially in the context of choosing the intensity of prophylactic treatment; should the aim be to prevent all bleeding or can a limited number of joint bleeds be accepted . In addition, it corroborates the observation that HRQoL is impacted by joint disease, rather than treatment received .…”

Navigating Speed Bumps on the Innovation Highway in Hemophilia Therapeutics

“…26 Extended throughout a lifetime, mean cumulative use is calculated to reach 19 Â 10 6 IU (vs 3.9 Â 10 6 IU for on demand treatment), with diminishing cost effectiveness. 26 The authors suggest that this model may provide some rationale for severe hemophilia A adults evolving from primary prophylaxis to a treatment plan that switches between nonprimary prophylaxis and on demand regimens based on rates of breakthrough hemorrhage and acceptable target levels of musculoskeletal bleeding protection, as well as both availability and cost of clotting factor. 26 And yet, the trends point to greater adoption of primary prophylaxis beyond childhood.…”

“…26 The authors suggest that this model may provide some rationale for severe hemophilia A adults evolving from primary prophylaxis to a treatment plan that switches between nonprimary prophylaxis and on demand regimens based on rates of breakthrough hemorrhage and acceptable target levels of musculoskeletal bleeding protection, as well as both availability and cost of clotting factor. 26 And yet, the trends point to greater adoption of primary prophylaxis beyond childhood. The United Kingdom Haemophilia Centre Directors Organization (UKHCDO) national guidelines recommend continuing primary prevention into adulthood for all except the mildest bleeding phenotypes.…”

A cost-effectiveness analysis of the prophylaxis versus on-demand regimens in severe hemophilia A patients under 12 years old in southern Iran

“…The economic evaluation studies on the cost-utility (CU) of the PR versus OD conducted throughout the world have achieved a wide range of results. The results of some studies have shown that the use of PR reduces joint bleeding and has more cost-effectiveness(CE) and CU than OD [16,17]. It is also estimated that the use of PR can reduce the demand for some health care sources in addition to reducing the bleeding and secondary degenerative orthopedic changes and improving the health-related quality of life [18].…”