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Treatments for primary immunodeficiency (PID) disorders (inborn errors of immunity)

Research and advances in therapies have resulted in improved health and a longer life for people with PID/IEI disorders. There are currently six main types of treatment options: 

  • Antibiotics
  • Immunoglobulin Replacement Therapy (IRT) - subcutaneous (SCIg) or intravenous (IVIg)
  • Immunomodulation – including biologics
  • Hereditary Angioedema (HAE) Treatments
  • Haematopoietic Stem Cell Transplantation (HSCT)
  • Gene Therapy

ANTIBIOTICS

Infections should be treated early, and antibiotics are often required. Some people may be prescribed long term antibiotics (prophylaxis) to reduce infections.

Medications against fungi, viruses and parasites may be needed to treat some conditions, and this may require long term access.

IMMUNOGLOBULIN REPLACEMENT THERAPY (IRT)

IRT is one of the most effective and commonly used treatments for some PID/IEI disorders. IRT can be given using intravenous immunoglobulin (IVIg) that is injected into the vein, typically in a hospital setting, or given at home using subcutaneous immunoglobulin (SCIg) injected under the skin.

These products are derived from pooled blood (plasma), are in limited supply, and access is restricted. Doctors must follow specific guidelines to ensure that the product goes to people most in need.

IMMUNOMODULATION – INCLUDING BIOLOGICS

There is an increasing number of drugs (medications) used to increase or decrease immune function.

Medications include corticosteroids, biologics such as monoclonal antibodies, small molecule inhibitors and other immunosuppressive drugs.

Medications that specifically target pathways in genetically defined PID/IEI disorders (known as targeted therapy or precision medicine) can be effective in some PID/IEI disorders that have failed standard therapy.

However, many of these are not funded for PID/IEI indications. Therefore, they are not accessible unless funding for the affected individual can be negotiated through hospital drug committees or through compassionate access from the drug company.

HEREDITARY ANGIOEDEMA (HAE) TREATMENTS

There are two main treatments for severe, acute HAE attacks:

  • Purified C1 esterase inhibitor for intravenous use in hospitals or at home; and
  • Icatibant which can be self-administered at home.

Prophylactic treatment is increasingly important in the management of HAE as it restores quality of life to patients who otherwise live with the ever present threat of debilitating attacks.

  • Older agents such as Tranexamic acid are available, but are not very effective in many people with HAE.
  • Danazol has been useful for some people with HAE, however it has been discontinued in Australia and is difficult to obtain from overseas. It has many potential side effects in people with HAE who are using it long term.
  • Newer agents are highly effective and have a very good safety profile.
  • C1 esterase inhibitor concentrate for IV and now SC use, is currently available but its use is very restricted to some people with very frequent HAE attacks.
  • Lanadelumab has been approved for use in Australia and New Zealand, but is not reimbursed. Clinical trials demonstrate its efficacy, safety and ease of use. Traditionally, it has taken years for such products to be made available to patients in Australia and New Zealand, so a more rapid process to allow access is needed.

Prophylactic management is rapidly evolving with a number of newer, more effective agents becoming available. Improved access to effective prophylaxis with be life-changing for many people with HAE.

HAEMATOPOIETIC STEM CELL TRANSPLANTATION (HSCT)

Current standard of care for definitive correction of SCID is HSCT, which must be performed urgently, as outcomes are best when performed at an early age with no active infection.

HSCT should only be undertaken in a specialist centre with suitable expertise and facilities to isolate and manage infants with SCID.

HSCT is also being used for other PID/IEI disorders in adults and children and can be curative, such as CGD and some combined immune deficiencies.

However, this form of treatment requires specialist expertise in centres with recognition and experience in PID/IEI.

GENE THERAPY

Rather than replacing a person’s immune system using stem cells from a donor (bone marrow transplant), for a small number of PID/IEI disorders with known gene defects, it is possible to treat patients using gene therapy.

This involves collecting stem cells from the affected individual, modifying them to include a healthy copy of the gene and returning them to the person to develop functioning immune cells.

Gene therapy is already commercially available in Europe for adenosine deaminase (ADA) SCID, with trials ongoing for several other PID/IEI disorders.

It is important to develop clinical expertise in managing gene therapy, including the collection, chemotherapy and reinfusion elements similar to HSCT.  

This is the model that has already been adopted for chimeric antigen receptor T (CAR-T) cell treatment in leukaemia, which is available in Australia.

Content updated November 2021