Executive summary

• Access to intravenous immunoglobulin in Australia
• Production and safety
• Rationale for developing criteria for intravenous immunoglobulin use
• Conditions considered for IVIg therapy

Intravenous immunoglobulin (IVIg) is a fractionated blood product made from pooled human plasma. It is registered for use in Australia for the treatment of a number of diseases where immunoglobulin replacement or immune modulation therapy is indicated. IVIg is used to treat a growing number of unregistered indications where there is some evidence for its utility. IVIg is a lifesaving therapy in appropriately selected patients and clinical circumstances.

Access to intravenous immunoglobulin in Australia

Since the 1980s, the demand for IVIg has greatly increased, both internationally and in Australia. In the late 1990s, worldwide shortages prompted action by Australian governments to ensure that IVIg was available for those patients most in need. Since that time, strategies to ensure supply have included:

• rationalising the use of IVIg by specifying conditions and limiting IVIg access under the National Blood Arrangements to those patients meeting the specified condition and eligibility criteria;
• increasing the manufacture of IVIg in Australia; and
• importing IVIg from overseas.

The average annual growth of IVIg use per capita in Australia from 2004–05 to 2010–11 was 14.18% per annum and the growth from 2009–10 to 2010–11 financial year was 9.46%. In 2010–11, the National Blood Authority spent, on behalf of Australian governments, $149 million on IVIg products. These are the product costs only and do not include costs associated with the collection of plasma for fractionation. The continual significant annual growth in IVIg use, the relatively high cost of IVIg products and the potential for supply shortages have maintained the focus of Australian governments on ensuring use remains consistent with an evidence-based approach and that IVIg is able to be accessed under the National Blood Arrangements for those patients with the greatest clinical need.

The Criteria for the clinical use of intravenous immunoglobulin in Australia describes current arrangements for access to IVIg funded under the National Blood Arrangements and the conditions for its use. It has been developed to assist clinicians and medical professionals identify the conditions and circumstances for which the use of IVIg is appropriate and funded.

Production and safety

For more than a decade, the local production of IVIg has fallen short of national consumption and overseas-sourced products have been used to supplement the Australian-made product. No plasma product, whether locally manufactured or imported from overseas, can be used in Australia unless the product has been assessed and approved by the Therapeutic Goods Administration (TGA). The TGA regulates the safety, quality, and efficacy of all IVIg products. The IVIg products funded in Australia under the National Blood Arrangements are available on the NBA website at www.nba.gov.au.

Rationale for developing criteria for intravenous immunoglobulin use

Before the adoption of the first edition of the Criteria, the management and use of IVIg in Australia was based upon the recommendations of a 2000 review conducted by the Blood and Blood Products Committee of the Australian Health Ministers’ Advisory Council. A recommendation of this review was that conditions for access to IVIg therapy undergo regular review to ensure that the therapeutic use of IVIg is kept current. These criteria were developed in response to that recommendation.

The term ‘criteria for use’ was chosen specifically to indicate a more directive framework to describe the circumstances, based on evidence and clinical experience, under which the clinical use of IVIg is considered appropriate to be funded in Australia.

Conditions considered for IVIg therapy

The Criteria for the clinical use of intravenous immunoglobulin in Australia (the Criteria) was first published in 2007 after a systematic review that was completed in mid-2006. In accordance with government commitments, the Jurisdictional Blood Committee (JBC) initiated a review of the Criteria in 2010. The review was limited to proposals to modify an entry or reassign the location (chapter) of an existing condition or to remove or add a condition to the Criteria. This resulted in the addition of seven rare conditions, removal of two conditions and the review of a limited number of conditions.

Twenty-seven formal submissions were considered and based on the information provided and expert opinion, a systematic review of the literature between 2006 and 2010 or a consensus process using expert clinical opinion was conducted.

The Criteria for the clinical use of intravenous immunoglobulin in Australia (second edition) identifies:

• Twelve conditions for which IVIg has an established therapeutic role. For these conditions, its use is supported by reasonable- quality evidence and expert opinion. For a number of conditions IVIg is first-line therapy in selected patients and may be the only established treatment option: for example, as replacement therapy in primary immunodeficiency disease.
• Twenty conditions for which IVIg has an emerging therapeutic role. For these conditions, there is clinical support for IVIg use in selected patients, although the quality of evidence supporting use is variable. For many conditions, IVIg is considered only as second or third-line therapy when standard therapies have been proven to be ineffective, become intolerable, or are contraindicated. Many of these conditions are rare and as a result, the evidence of benefit is often patchy and inconclusive. Other conditions are more prevalent, yet the evidence of benefit is either conflicting or uncertain, requiring more research, or the use of IVIg represents a relatively new direction in their management and evidence of benefit is still emerging. For these conditions, the collection of effectiveness data is of particular importance.
• Twenty-nine conditions for which IVIg is used in exceptional circumstances only. These conditions rarely, if ever, require IVIg use, either because there are safe and effective alternative therapies, or because the evidence of benefit does not justify use in most cases. IVIg is considered to have a therapeutic role only in exceptional circumstances, such as in urgent or life-threatening circumstances, or in circumstances in which significant morbidity would be expected and other clinically appropriate therapies have been exhausted or are contraindicated.
• Thirty-six conditions for which IVIg therapy is not supported or funded. IVIg therapy for these conditions is not supported or funded 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.

Where the therapeutic role of IVIg is well established or there is emerging evidence of a role for IVIg therapy in selected patients, a structured proforma is provided. The proforma details the diagnostic parameters and criteria that need to be met for IVIg to be accessed under the National Blood Arrangements. The Criteria generally refer to matters such as patient selection, particular disease characteristics, disease severity, and any requirement for other treatments to have been demonstrated as unsuccessful before IVIg is considered.

The national implementation of the Criteria facilitates access and use of IVIg in a manner consistent with the evidence base, for the treatment of patients who are likely to benefit, and for whom there are no safe and effective alternative treatments.