# Extravascular factor IX after gene therapy in hemophilia B, does it matter?

## TL;DR

Gene therapy for hemophilia B may not fully prevent the need for additional factor IX treatment during trauma or surgery, and more research is needed to determine the best product to use.

## Contribution

The paper highlights the lack of evidence on optimal exogenous factor IX products to use after gene therapy and emphasizes the need for real-world data.

## Key findings

- Gene therapy does not fully protect most persons with hemophilia B in case of trauma or surgery.
- The optimal adjunctive factor IX product after gene therapy has not yet been determined.
- More real-world data are needed on the use of exogenous factor IX after gene therapy.

## Abstract

Gene therapy will very likely change the treatment paradigm of hemophilia B in the coming years. For the majority of patients, adjunctive exogenous factor (F)IX clotting factor concentrate will continue to be needed in case of surgery or bleeding. However, there is insufficient evidence on the optimal FIX product to be used in these circumstances, given the differences in body distribution between the currently available products. Unknown factors include the behavior of FIX Padua in the extravascular space and its contribution to hemostasis. Other issues are the potential importance of the presence of cross-reactive material and the discrepancies between different assays in measuring FIX activity. In conclusion, even after gene therapy, the differences between different FIX products remain relevant for optimal bleeding and perioperative management. Thus, real-world data on the use of exogenous FIX after gene therapy are needed to determine the preferred exogenous FIX concentrate.

•Gene therapy does not fully protect most persons with hemophilia B in case of trauma or surgery.•The optimal adjunctive factor IX product after gene therapy has not yet been determined.•The role of cross-reactive material and the body distribution of the product should be evaluated.•More real-world data are needed on the use of exogenous factor IX after gene therapy.

Gene therapy does not fully protect most persons with hemophilia B in case of trauma or surgery.

The optimal adjunctive factor IX product after gene therapy has not yet been determined.

The role of cross-reactive material and the body distribution of the product should be evaluated.

More real-world data are needed on the use of exogenous factor IX after gene therapy.