Primary Risk Drivers
Below is a snapshot of domains that materially influence the MARA Rating.
Clinical effectiveness
The clinical evidence for imlifidase is limited and primarily based on short-term outcomes from non-UK based, uncontrolled studies. While it shows some ability to convert positive crossmatches to negative ones, the lack of long-term data and the high rates of antibody-mediated rejection raise concerns about its overall effectiveness in improving transplant outcomes.
Cost effectiveness
The cost-effectiveness estimates for imlifidase are within the acceptable range for Healthcare resources, with the most plausible ICER being less than £30,000 per QALY gained. However, there is substantial uncertainty surrounding these estimates due to the limited data.
Quality of life
The evidence suggests that imlifidase can improve access to kidney transplantation for highly sensitised patients, which may lead to improvements in quality of life compared to remaining on dialysis. However, the data on HRQoL improvements is not robust and primarily anecdotal.
Supporting Domains
Safety and Adverse Effects
Imlifidase has a manageable safety profile, with most adverse events being mild to moderate. However, there are notable concerns regarding the high rates of antibody-mediated rejection, which could undermine the perceived benefits.
Comparator Selection
The trials for imlifidase lacked a comparator arm, relying instead on uncontrolled studies. This raises concerns about the validity of the evidence, as it does not adequately compare imlifidase to existing treatment options.
Patient Population and Subgroups
The proposed patient population for imlifidase is appropriate, targeting highly sensitised individuals who are unlikely to receive a transplant. The committee recognized the need for careful consideration of this population within the context of Healthcare clinical practice.
Care Pathway Integration
Integrating imlifidase into existing transplant pathways is expected to be challenging, requiring protocols to manage cold ischaemic time and ensure appropriate patient selection. This indicates a significant impact on current practices.
Resource Use and Cost Implications
The resource implications of imlifidase are manageable, with the potential for cost savings by reducing the time patients spend on dialysis. However, the overall budget impact remains uncertain due to the limited data.
Evidence Quality and Robustness
The evidence base for imlifidase is limited, primarily consisting of short-term data from uncontrolled studies. This raises concerns about the robustness and generalizability of the findings, necessitating further data collection.
Uncertainty, Sensitivity, and Broader Impacts
There is significant uncertainty regarding the long-term outcomes and cost-effectiveness of imlifidase, particularly in relation to its integration into existing pathways and the potential impact on equity of access for highly sensitised patients.
