Conditions: A-B

Diagnosis of acquired hypogammaglobulinaemia secondary to haematological malignancies or stem cell transplantation with:

• recurrent or severe bacterial infection(s) and evidence of hypogammaglobulinaemia (excluding paraprotein);

OR

• Hypogammaglobulinaemia with IgG <4 g/L (excluding paraprotein).

Note: For data tracking purposes, the type of malignancy being treated should be recorded with each request for IVIg.

The following conditions should not be approved under this indication:

1. HIV in children;
2. Transplantation-related immunomodulation (solid organ transplantation;
3. Secondary hypogammaglobulinaemia (including iatrogenic immunodeficiency.

Six-monthly review to assess clinical benefit. Cessation of IVIg should be considered, at least after each 12 months of therapy, extended as required to enable cessation of therapy in September/October, with repeat clinical and/or immunological evaluation before re-commencement of therapy.

Written confirmation from the treating physician that:

• an annual review has been undertaken;
• the patient had demonstrated clinical benefit;
• a trial period of cessation of IVIg for the purpose of immunological evaluation is medically contraindicated on safety grounds.

In principle, IVIg should be continued or renewed only if there is a demonstrated clinical benefit.

Maintenance dose: 0.4 g/kg every four weeks, modified to achieve an IgG trough level of at least the lower limit of the age-specific serum IgG reference range.

Loading dose: One additional dose of 0.4 g/kg in the first month of therapy is permitted if the serum IgG level is <4 g/L.

Subcutaneous administration of immunoglobulin can be considered as an alternative to IVIg. A suggested dose is 0.1 g/kg lean body mass every week modified to achieve an IgG trough level of at least the lower limit of the age- specific serum IgG reference range.

Refer to the current product information sheet for further information.

The aim should be to use the lowest dose possible that achieves the appropriate clinical outcome for each patient.

1. ADEM unresponsive to steroid therapy or where steroids are contraindicated (e.g. suspicion of CNS infection).
2. Recurrent or multiphasic ADEM unresponsive to steroid therapy or where steroid therapy has become intolerable or is contraindicated.

ADEM is a monophasic inflammatory condition of the central nervous system that usually presents in children and young adults. It typically occurs following a viral prodrome with multifocal neurological disturbance and altered conscious state. ADEM usually follows a monophasic course, but patients may experience recurrence of the initial symptom complex (recurrent ADEM) or a second episode of ADEM (multiphasic ADEM). The majority make a full recovery.

ADEM is thought to have an autoimmune basis. Pathologic similarities to experimental allergic encephalomyelitis (EAE), an animal model of inflammatory demyelination, support this theory. It is postulated that a common antigen shared by an infectious agent and a myelin epitope results in an autoimmune response.

Patients show multiple demyelinating lesions on magnetic resonance imaging (MrI) in the deep and subcortical white matter. The differential diagnosis includes other inflammatory demyelinating disorders, such as multiple sclerosis, optic neuritis and transverse myelitis.

High-dose corticosteroids are first-line treatment of ADEM. IVIg has been used for patients who fail to respond to steroid therapy or in patients where steroids are contraindicated. Most patients with ADEM recover completely over a period of six weeks from onset.

There is no biological marker for ADEM. Diagnosis is by clinical recognition of the multifocal neurological disturbance and altered conscious state, with the typical MRI findings of demyelination.

1. ADEM unresponsive to steroid therapy or where steroids are contraindicated (e.g. suspicion of CNS infection).

Note: Assessment by a neurologist is recommended, but not mandatory.

OR

2. Recurrent or multiphasic ADEM unresponsive to steroid therapy, or where steroid therapy has become intolerable or is contraindicated, with assessment by a neurologist mandatory.

Objective evidence of improvement in relapse rate in comparison to pre-treatment levels.

Six-monthly review by a neurologist is required for recurrent or multiphasic ADEM.

Induction: 2 g/kg in 2 to 5 divided doses.

Maintenance dose: For recurrent or multiphasic ADEM only: 0.4–2 g/kg, 4–6 weekly.

Aim for the minimum dose to maintain optimal functional status and prevent relapses.

In recurrent or multiphasic ADEM, assessment by a neurologist is mandatory.

Dosing above 1 g/kg per day is contraindicated for some IVIg products.

Refer to the current product information sheet for further information.

The aim should be to use the lowest dose possible that achieves the appropriate clinical outcome for each patient.

[Includes acute lymphoblastic or lymphoid leukaemia (ALL) and acute myeloblastic leukaemia (AML)].

IVIg may be considered in cases of ALL or AML with neutropenic sepsis in patients aged ≤15 years in whom conventional antimicrobial therapy has been ineffective and who have life-threatening infection.

Refer to the current product information sheet for further information.

The aim should be to use the lowest dose possible that achieves the appropriate clinical outcome for each patient.

Evidence of probable benefit (Category 2a).

Control of vasculitic activity in rare cases of ANCA-positive systemic necrotising vasculitis failing to respond to corticosteroids and cytotoxic immunosuppression.

ANCA associated systemic necrotising vasculitides are life-threatening immune-mediated inflammatory diseases comprising one of four clinical syndromes:

1. Wegener granulomatosis;
2. Microscopic polyangiitis;
3. Churg–Strauss syndrome; and
4. ANCA (PR3 or MPO)-positive idiopathic rapidly progressive glomerulonephritis.

In these cases the ANCA specificity is directed against the neutrophil cytoplasmic antigens proteinase 3 (PR3) and myeloperoxidase (MPO). ANCA that lack MPO or PR3 specificity tend to be non-specific. Biopsy of affected tissue is required to establish the diagnosis.

Standard combinations of corticosteroids and cytotoxic immunosuppression are generally effective at controlling disease, but relapses are common. IVIg has a limited role as one of several therapeutic options in relapsing disease.

MPO or PR3 ANCA-positive systemic necrotising vasculitis with both of the following:

1. Current (or within the previous six months) standard cytotoxic immunosuppressive ANCA-vasculitis regimens;

AND

2. Persisent active disease.

Initial therapy

• Six-month review assessing evidence of clinical benefit.
• Reduction in the Birmingham vasculitis activity score of more than 50% after three months.
• Erythrocyte sedimentation rate and C-reactive protein concentration.
• ANCA titre.

2 g/kg in single or divided doses.

Dosing above 1 g/kg per day is contraindicated for some IVIg products.

Refer to the current product information sheet for further information.

The aim should be to use the lowest dose possible that achieves the appropriate clinical outcome for each patient.

IVIg therapy may be indicated during pregnancy when there is a history of autoimmune congenital heart block in at least one previous pregnancy and maternal SS-A and/or SS-B antibodies are present.

Refer to the current product information sheet for further information.

The aim should be to use the lowest dose possible that achieves the appropriate clinical outcome for each patient.

Small case studies only - insufficient data (Category 4a).

To reduce haemolysis in patients not responding to corticosteroid therapy.

Small case studies only; insufficient data (Category 4a).

AIHA is a rare but serious autoimmune disease in which an individual’s antibodies recognise antigens on their own red blood cells. AIHA presents as an acute or chronic anaemia characterised by the occurrence of biochemical parameters of red cell destruction associated with a positive direct antiglobulin test indicating the presence of antibodies and/ or complement on the red cell surface. It may be secondary to a number of underlying disorders or drugs.

Investigations

A full blood count will confirm the presence of anaemia. A peripheral blood smear may reveal evidence of spherocytes along with polychromasia due to reticulocytosis. A direct antiglobulin test is usually positive, the serum lactate dehydrogenase is raised, and there is a reduction in serum haptoglobin.

Prognosis

The prognosis of AIHA is good in most cases although severe refractory AIHA can cause cardio-respiratory problems because of severe anaemia, especially in adults.

Standard therapy

Corticosteroid administration is the cornerstone of therapy. For those with relapsing disease, splenectomy and immunosuppression are second line treatments while anti-CD20 antibodies have shown promise in individual cases of refractory disease.

1. Symptomatic or severe AIHA (Hb <60 g/L, except patients with co-morbidities) refractory to conventional therapy with corticosteroids;

OR

2. As a temporising measure before splenectomy;

OR

3. As initial and maintenance therapy in AIHA in patients unsuitable for splenectomy or immunosuppression.

Patients in whom a trial of corticosteroids has not been undertaken.

• resolution of haemolytic anaemia (rising haemoglobin concentrations, falling bilirubin and LDH).
• Clinical improvement in symptoms and signs.

Up to 2 g/kg as a single or divided dose.

Dosing above 1 g/kg per day is contraindicated for some IVIg products.

Refer to the current product information sheet for further information.

The aim should be to use the lowest dose possible that achieves the appropriate clinical outcome for each patient.

Autoimmune neutropenia is a rare disorder caused by peripheral destruction of antibody-sensitised neutrophils by cells of the reticuloendothelial system. IVIg may be considered among treatment options in rare circumstances when the standard treatment of G-CSF fails.

Refer to the current product information sheet for further information.

The aim should be to use the lowest dose possible that achieves the appropriate clinical outcome for each patient.

Small case studies only - insufficient data (Category 4a).

Uveitis refers to inflammation of the uvea of the eye and can be caused by infection, exposure to toxins or autoimmune disorders. Symptoms may include redness of the eye, blurred vision, unusual sensitivity to light, dark floating spots in the vision and eye pain. Ocular inflammation of this kind may threaten sight and be resistant to standard immunosuppression.

IVIg therapy may be considered for immune-mediated, sight-threatening uveitis with persistent activity despite both oral corticosteroid and systemic immunosuppressive therapy. Uveitis of non-immune origin is not indicated.

Recommended dose is 1.5 g/kg/month for three months, with further maintenance dependent upon evidence of significant improvement in visual acuity and ocular inflammation.

Dosing above 1 g/kg per day is contraindicated for some IVIg products.

Refer to the current product information sheet for further information.

The aim should be to use the lowest dose possible that achieves the appropriate clinical outcome for each patient.

Small case studies only - insufficient data (Category 4a).

Bullous pemphigoid resistant to topical and systemic glucocorticoids and immunosuppressive therapy.

Small case studies only; insufficient data (Category 4a).

BP is a rare disease of elderly people characterised by tense blisters and vesicles with a prominent inflammatory component. The cause is unknown. Lesions result from a failure of basal keratinocytes to adhere to the epidermal basement membrane.

The course of BP is characterised by exacerbations and remissions. Pruritis is a common feature and an increase in pruritis may herald an exacerbation.

In most patients, BP is not a life-threatening disease. The side effects of systemic immunosuppressive therapy need to be managed. In most patients, the disease spontaneously clears within six years and all medication can be stopped. In a small group, the disease recurs after treatment is stopped. Skin infection is the most common complication.

A submission by the Australasian College of Dermatologists recommends IVIg use in BP only in severe cases where improvement with conventional therapy is not readily achieved.

Moderate to severe disease diagnosed by a dermatologist

AND

1. Corticosteroids or immunosuppressive agents are contraindicated;

OR

2. Condition is unresponsive to corticosteroids and immunosuppressive agents;

OR

3. Presenting with severe side effects of therapy.

• Response demonstrated at review at six months. Improvement to be demonstrated for continuation of supply.
• Reduction in recurrence of disease or relapse.
• Ability to reduce dose or discontinue other therapies.
• Improved quality of life.
• Resolution of blisters and healing of affected skin.
• Resolution of pruritis.

Efficacy demonstrated with doses of at least 2 g/kg per monthly treatment cycle.

Dosing above 1 g/kg per day is contraindicated for some IVIg products.

Refer to the current product information sheet for further information.

The aim should be to use the lowest dose possible that achieves the appropriate clinical outcome for each patient.