Criteria for the Clinical Use of Intravenous Immunoglobulin (IVIg) in Australia - Frequently Asked Questions

Last updated on 23 December 2009

ABOUT THE CRITERIA

1. Why was the Criteria document developed?

Intravenous immunoglobulin (IVIg) is a life-saving therapy in appropriately selected patients and clinical settings. The new Criteria for the Clinical Use of Intravenous Immunoglobulin in Australia (the Criteria) was developed to ensure IVIg use remains consistent with the available evidence and for the treatment of patients who are likely to derive a genuine health benefit. The Criteria updates recommendations on the use and supply of IVIg developed in 2000.

2. What are the major differences between the 2000 AHMAC IVIg guidelines and the new Criteria?

The Criteria document differs from the 2000 AHMAC IVIg guidelines in two important ways.

Firstly, an increased number and broader range of conditions are considered. Ninety-four conditions or groups of conditions are considered. The Criteria describes 12 conditions for which IVIg use has an established therapeutic role; 22 for which IVIg has an emerging therapeutic role; and 25 for which IVIg should be used in exceptional circumstances only, such as in urgent or life-threatening circumstances. The Criteria also lists 36 conditions for which IVIg therapy is not supported at this time, either because there is evidence of no benefit, insufficient evidence of benefit, or some evidence of benefit but preferred alternative therapies are available. The list of ‘non-indications’ includes some that were considered Category 2 indications in the 2000 guidelines, for example, asthma.

Secondly, the Criteria document describes explicit qualifying, exclusion and review criteria that should be fulfilled if IVIg is to be used. These generally refer to matters such as particular disease characteristics, disease severity and any requirement for other treatments to have been demonstrably unsuccessful before IVIg is considered.

3. For what new conditions can funded IVIg be used under the Criteria?

Neonatal haemochromatosis, toxic epidermal necrolysis/Steven Johnson syndrome and toxic shock syndrome are important new conditions for funded IVIg. IVIg is also now available for use in the treatment of severe relapsing-remitting multiple sclerosis during pregnancy and in cases unresponsive to standard therapies. Multiple sclerosis was formerly a Category 3 indication in the 2000 guidelines.

4. For what conditions is funded IVIg no longer accessible under the new Criteria?

The priority of IVIg use has been reduced in favour of alternative therapies and is now considered exceptional practice for the treatment of acute childhood leukemia and, with the advent of antiretroviral therapy, paediatric cases of HIV infection. Also, a number of conditions that were classified as Category 2 indications in the 2000 guidelines have been assessed as ‘non-indications’ in the Criteria. These include adrenoleukodystrophy, aplastic anaemia/pancytopenia, asthma, autism, Crohn’s disease, haemolytic uraemic syndrome, Henoch-Schonlein purpura, HIV/AIDS in adults, paraneoplastic cerebellar degeneration with Yo antibodies, rheumatoid arthritis, sensory neuropathy with anti-Hu antibodies, sickle cell anaemia and ulcerative colitis. IVIg is no longer available for these conditions under the cost-shared arrangements of the National Blood Agreement (see Question 9 below)

5. How are patients with an IgG subclass deficiency classified under the new Criteria?

Under the Criteria, patients previously receiving IVIg therapy for IgG subclass deficiency should be reviewed under the condition ‘Specific antibody deficiency’ if they are no longer experiencing serious infections. It is now generally agreed that IgG subclass level estimation in serum is relatively poorly predictive of infectious risk and is of limited value in the definition of those patients most likely to benefit from IVIg therapy. Many patients with previously diagnosed IgG subclass deficiency and recurrent infection on IVIg may have specific functional antibody deficits.

5a. Why is a distinction made between IgG subclass deficiency and Specific Antibody Deficiency?

Specific antibody deficiency indicates a failure of the immune system to mount a protective antibody response to exposure to an organism, and is typically assessed using vaccine responses. IgG subclasses do not provide the same functional information. There is therefore a need for careful diagnosis and distinction between these two conditions to determine the most appropriate therapeutic regimen. It is now generally agreed that IgG subclass level estimation in serum is a poor predictor of infectious risk and is of limited value in identifying those patients most likely to benefit from IVIg therapy.

Many patients with previously diagnosed IgG subclass deficiency and recurrent infection on IVIg may have specific functional antibody deficits. AHMAC 2000 criteria included IgG subclass deficiency at a “Category 1 indication” with the prerequisite that “Failure of antibody response to vaccine antigens” is demonstrated. In practice this important requirement was seldom imposed.

Host antibody production and responses to vaccine challenge cannot be readily assessed in individuals currently receiving IVIg hence the need for an extended washout period in accordance with the half-life of the IVIg product used.

6. Why are diagnoses with the same level of evidence in different chapters?

The basis for allocating particular diagnoses and criteria to Chapter 5,6, 7 and 8 was overall consideration of:

the level of published evidence
the clinical expertise (including colleges and societies)
access to alternative therapy.

7. How frequently will the Criteria be reviewed and updated?

Governments recognise the need for the conditions identified and the criteria for the use of IVIg to be regularly reviewed to take account of the evolving processes of disease diagnosis, treatment and outcome evaluation. It is proposed that the Criteria will be reviewed three-yearly, with the review process commencing two years after the release of each new version, allowing 12 months for consultation and drafting.

8. What is the process for including a new clinical indication in the Criteria?

Proposals for new clinical indications and the supporting evidence should be submitted during the document review period, which will commence two years after the release of each new version.

ACCESS to IVIg

9. How do I access IVIg for my patient whose condition is not eligible for IVIg under the Criteria?

When IVIg can not be accessed under the National arrangements, if the clinician considers that the patient would benefit from IVIg therapy, the clinician may still obtain IVIg through the Jurisdictional Direct Order (JDO) provision. Note that procedures for accessing IVIg JDO arrangements will vary and only imported IVIg is available under JDO arrangements.

10. What plans do Australian governments have to ensure an adequate supply of IVIg?

The availability of IVIg in Australia relative to clinical need has been reviewed repeatedly since at least the early 1990s. Three approaches have been used to ensure an adequate supply:

aligning the use of IVIg to conditions and circumstances where there is evidence of benefit;
increasing the manufacture of domestic IVIg; and
importing IVIg from overseas suppliers.

In 2005, the National Blood Authority introduced arrangements for the contingent supply of overseas IVIg. Under this arrangement, overseas IVIg is used to supplement the domestic IVIg supply in the event domestic production does not meet demand.

11. How can I order IVIg under the Criteria?

There will be no changes to the procedures for ordering or distributing IVIg under the Criteria.

In most states/territories, IVIg is ordered from TMS (Transfusion Medicine Services) at the ARCBS. Distribution procedures from the ARCBS vary slightly between jurisdictions, but this will not change as a result of the introduction of the Criteria.

12. Will the government fund doses that exceed the range published in the Criteria?

The growth in demand for IVIg has prompted action by Australian governments to ensure it is reserved for use in those with the greatest need. While the dose range published in the Criteria is indicative only, it is important that IVIg is prescribed judiciously. As such, where safe, effective and affordable alternative therapies exist, these are considered preferable to IVIg. When IVIg is used, the lowest dose for the shortest duration required to achieve the desired outcome should be chosen. For ongoing therapy, the achievement of measurable clinical outcomes is a requirement and IVIg should not be continued in patients with no demonstrable clinical benefit.

IVIg PRODUCTS

13. What IVIg products are available in Australia?

IVIg products used in Australia, whether locally produced or imported, must be assessed and approved by the Therapeutic Goods Administration (TGA). The TGA regulates the safety, quality and efficacy of IVIg products.

Four overseas manufactured IVIg products have been approved and registered for use in Australia. Two of these (Sandoglobulin ® and Octagam ®) are presently used to supplement supplies of the domestic product (Intragam ®P).

14. Does imported IVIg meet the same safety standards as domestic IVIg?

Yes. All blood, blood components and plasma derivatives supplied in Australia are regulated under the Therapeutics Goods Act 1989 by the Therapeutic Goods Administration (TGA). The TGA is responsible for enforcing standards within the blood sector to ensure blood products meet appropriate safety, quality and efficacy requirements. It also registers individual products for specific uses.

The TGA undertakes a comprehensive assessment of the safety, quality and efficacy of all domestic and imported plasma products before they can be registered on the Australian Register of Therapeutic Goods and approved for supply in the Australian market. The TGA licences (manufacturers in Australia) or certifies (manufacturers located overseas) the facilities where plasma products are manufactured against standards of Good Manufacturing Practice (GMP). Audits are conducted to ensure ongoing compliance with GMP.

15. Where can I obtain information about IVIg products?

Information about IVIg products is available at www.nba.gov.au and www.transfusion.com.au and also at the websites of the pharmaceutical companies www.csl.com.au and www.octapharma.com

Members of the ARCBS TMS team can also assist with advice.

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