This protocol addresses patients with hereditary C1 inhibitor deficiency who have high hereditary angioedema (HAE) disease activity and whose attacks remain inadequately controlled despite on-demand therapy and a full course of first-line long-term prophylaxis.
Long-term prophylaxis should be individualized in HAE type 1/2, taking into account disease activity, patient quality of life, available health care resources, and failure to achieve adequate control through appropriate on-demand therapy. High disease activity with persistent breakthrough attacks signals the need to escalate beyond first-line measures.
The patient has already received first-line long-term prophylaxis — which may include plasma-derived C1 inhibitor, lanadelumab, or berotralstat — but did not achieve the primary goal: complete disease control, meaning no longer having angioedema attacks. This unmet target is the escalation trigger for the current protocol.
This protocol defines a second-line long-term prophylaxis strategy. It centres on a specific class of attenuated androgens, applied at the minimal effective dose, along with guidance on when and how to adjust. A separate, off-label alternative is specified for circumstances in which all standard first-line options are unavailable.
The full regimen, dosing algorithm, monitoring criteria, and decision rules are in the structured protocol below.DOI: 10.1111/all.15214