Department of Medicine

Hereditary Angioedema and Primary Immunodeficiency

Mar 6, 2019
Dr. Stephen Betschel

Dr. Stephen BetschelDr. Stephen Betschel The arena or rare diseases has been the focus of new treatment development as well as novel delivery mechanisms of existing treatments. Hereditary Angioedema (HAE) is a rare disease that results from the lack of production of C1-INH inhibitor which is a key regulator in the production of bradykinin. Unregulated production of bradykinin leads to significant swelling of extremities, gut mucosa, and retro-pharynx. The latter can obstruct the airway and prove fatal in one third of undiagnosed patients. Newer treatment for either acute attacks of angioedema or prophylaxis has focused on replacing C1-INH, blocking bradykinin, or kallikrein inhibition.

One of the newest agents, which will likely be licenced in Canada in the near future, will be a prophylactic subcutaneously injected monoclonal antibody which inhibits kallikrein production and reduces swelling attacks to nearly zero. Patients historically have had not had access to such efficacious and easy to administer therapy. Additionally, newer oral agents are being investigated in Phase 3 trials that inhibit kallikrein production.

These newer developments in the treatment of HAE will have a profound impact on the lives of patients with HAE. The rate of development has been considerable when considering that less than a decade ago in Canada there was only one licenced drug (tranexamic acid) for prophylactic treatment for HAE and it was often poorly tolerated.

These new and rapidly evolving developments require ongoing review of the evidence and updating national and international treatment guidelines. The Division of Clinical Immunology and Allergy has led the way for this important initiative historically and will continue to do so with a new international guideline to be held in Toronto in November 2018.

Primary immunodeficiency is often overlooked in adults as it is often considered a disease of pediatrics. In fact, most primary immunodeficiency exists in people over the age of 18. Antibody deficiency is the most common primary immunodeficiency. Historically, the focus of treatment in antibody deficiency is replacing antibodies with intravenous immunoglobulins (IVIG). This is typically done in a hospital setting and requires significant resources to facilitate.

However, immunogloblulins can be given via a subcutaneous route by patients themselves. This change in modality facilitates transferring of care from a hospital setting to the home which is associated with improved quality of life for patients and better healthcare utilization. As such there has been a significant transition of patients from the hospital to their homes helping to normalize the lives of patients who require this treatment not only for patients with primary immunodeficiencies but for other patients who require ongoing immunoglobulin therapy such as in some secondary immunodeficiencies such as CLL, or neurologic conditions such as CIDP.

The shift to home therapy is still relatively new and awareness that it exists is growing but not yet optimal. The focus in the future will be on raising awareness of this important treatment option as well as developing newer delivery mechanisms to simplify treatment even further and enable patients to live a normal life.