Conditions: K-M

Clear evidence of benefit (Category 1).

Kawasaki disease is an acute, febrile, multi-system disease of children and young infants often involving the coronary arteries. Coronary artery aneurysms may occur from the second week of illness during the convalescent stage.

The cause of the condition is unknown but there is evidence that the characteristic vasculitis results from an immune reaction characterised by T-cell and macrophage activation to an unknown antigen, secretion of cytokines, polyclonal B-cell hyperactivity, and the formation of autoantibodies to endothelial cells and smooth muscle cells. It is likely that in genetically susceptible individuals, one or more uncharacterised common infectious agents, possibly with super-antigen activity, may trigger the disease.

Diagnosis

A diagnosis of Kawasaki disease is generally made if fever of four or more days’ duration is associated with at least four of the following changes, which often appear sequentially:

• bilateral (non-purulent) conjunctival injection;
• changes of the mucous membranes of the upper respiratory tract and oropharynx, including diffuse redness of pharyngeal mucosa, dry fissured lips, red fissured lips, and/or ‘strawberry tongue’;
• changes of the extremities, including peripheral erythema, peripheral oedema, and subsequent periungual or more generalised desquamation;
• polymorphous rash;
• cervical lymphadenopathy.

A diagnosis of Kawasaki disease may be made if fever and fewer than four of the changes listed above are present where there is strong clinical suspicion of Kawasaki disease (refer to Newburger 2004). Between 10% and 20% of cases, particularly in younger infants, present with fever and fewer than four of the listed criteria. Expert advice should be sought.

Data support the use of IVIg while there is ongoing inflammation (usually taken as ongoing fever or raised acute inflammatory markers). Prognosis is worse if IVIg is used 10 days post-onset, but should be used at any time if there is evidence of inflammation. Up to 15% of patients do not respond to initial IVIg therapy. Consensus is for re- treatment with 2 g/kg of IVIg before considering steroids.

Clinical diagnosis of Kawasaki disease by a paediatrician or immunologist.

2 g/kg in a single dose over 10–12 hours unless cardiac function necessitates the administration of a prolonged or divided treatment dose, usually once only.

Re-treatment with 2 g/kg in a single dose may be given when there is ongoing 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.

Pre-transplantation

Patients in whom an antibody or antibodies prevent transplantation (donor specific anti-human leukocyte antigen (HLA) antibody/ies or anti-blood group antibody).

Post-transplantation

To treat steroid-resistant acute rejection which may be cellular or antibody mediated.

For prevention and/or treatment of rejection where other therapies are contraindicated or pose a threat to the graft or patient.

Clear evidence of benefit (Category 1).

Transplant rejection occurs when a recipient’s immune system attacks a transplanted organ or tissue. Despite the use of immunosuppressants, one or more episodes of rejection can occur after transplantation. Both cellular and humoral (antibody-mediated) effector mechanisms can play a role.

The presence and pattern of rejection need to be established by biopsy. Laboratory tests to assess the presence and strength of antibodies to the donor antigens can provide additional useful information. Clinical assessment, blood tests, ultrasound and nuclear imaging are used primarily to exclude other causes of organ dysfunction.

Acute cellular rejection occurs in 15–30% of renal transplants and is responsive to steroids in more than 90% of cases. When rejection is steroid resistant, IVIg is a safer therapy than anti-T cell antibody therapy with equal efficacy.

Antibody mediated rejection (AbMR) occurs in 5–10% of renal transplants that have been performed with a compatible cross match. Before the use of IVIg and plasma exchange, AbMR failed to respond adequately to therapy in most cases. Additionally, complications from therapy were severe and sometimes fatal. AbMR responds to IVIg with or without plasma exchange in more than 85% of patients.

Pre-transplantation

Patients in whom an antibody or antibodies prevent transplantation (donor-specific anti-HLA antibody/ies or anti-blood group antibody).

Post-transplantation

1. Biopsy proven cellular rejection unresponsive to steroids with clinical evidence of graft dysfunction;

OR

2. Acute antibody mediated rejection with clinical evidence of graft dysfunction;

OR

3. As treatment or prophylaxis for rejection where conventional immunosuppressive therapy is contraindicated, for example:
   • in a patient with life-threatening infection in whom conventional immunosuppression will place the patient at even greater risk;
   • when the transplant is at risk (e.g. due to BK virus infection).

• Allograft organ function tests.
• Biopsy response.
• Laboratory monitoring of anti-HLA antibody and/or anti-blood group antibody responses.
• Duration of graft and patient survival.
• Reversal of clinical graft dysfunction.

IVIg with plasma exchange: 0.1 to 0.5 g/kg post exchange.

IVIg alone: 2 g/kg to a maximum of 140 g as a single dose, or 2 to 3.5 g/kg in a divided dose.

When IVIg is used alone, further doses may be warranted two to four weeks after initial therapy depending on clinical response and/or biopsy findings.

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.

Short-term therapy for severely affected nonparaneoplastic LEMS patients.

Evidence of probable benefit (Category 2a).

LEMS is a disorder of neuromuscular transmission first recognised clinically in association with lung cancer and subsequently in cases in which no neoplasm was detected.

Patients with LEMS have a presynaptic neuromuscular junction defect. The clinical picture is characterised by proximal muscle weakness with augmentation of strength after exercise, mild oculomotor signs, depressed deep tendon reflexes and autonomic dysfunction (dry mouth, constipation, erectile failure).

1. Mandatory assessment by a neurologist;

AND

2. Severely affected nonparaneoplastic LEMS patients in whom other therapy (e.g. with 3,4-diaminopyridine) has failed.

IVIg should be used for three to six months (three to six courses) before determining whether the patient has responded. If there is no benefit after three to six courses, IVIg therapy should be abandoned.

Review

Regular review by neurologist is required: frequency as determined by clinical status of patient. Initial review three to six monthly.

For stable patients on maintenance treatment review by a neurologist is required at least annually.

Effectiveness

Clinical documentation of effectiveness is necessary for continuation of IVIg therapy.

Effectiveness can be demonstrated by objective findings of either:

1. Improvement in functional scores activities of daily living (ADL) or quantitative muscle scores or Medical Research Council (MRC) muscle assessment;

OR

2. Stabilisation of disease as defined by stable functional scores (ADLs) or quantitative muscle scores or MRC muscle assessment after previous evidence of deterioration in one of these scores.

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

Maintenance: 0.4–1 g/kg, 2–6 weekly.

Aim for minimum dose to maintain optimal functional status.

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.

There appears to be a role for IVIg in nonparaneoplastic limbic encephalitis associated with neuronal antibodies to cell surface antigens. This includes VGKC antibodies, as well as NMDA receptor antibodies and AMPA receptor antibodies.

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)

IVIg may be indicated in select cases, in combination with tumour therapy (tumour resection and/or oncological treatment) where the latter has not led to an improvement in the neurologic syndrome; where other immunomodulatory therapies are contraindicated or have failed; or if the neurologic features warrant urgent intervention.

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)

First-line therapy for MMN.

Clear evidence of benefit (Category 1).

MMN is a relatively rare disorder characterised by slowly progressive, asymmetric, predominately distal limb weakness without sensory impairment. Weakness often begins in the arms and the combination of weakness, wasting, cramps and fasciculations may suggest a diagnosis of motor neuron disease. However, clinical examination may demonstrate that the pattern of weakness follows the distribution of individual nerves rather than a spinal segmental pattern.

Investigations will typically show conduction block on nerve conduction studies. IgM anti-GM-1 antibodies have been reported in a large number of patients with MMN and provide confirmatory evidence but are not essential for the diagnosis.

Patients who have multifocal motor neuropathy, with a typical clinical phenotype, with or without persistent conduction block, as diagnosed by a neurologist.

• Presence of upper motor neuron signs.
• Significant sensory impairment without an adequate alternative explanation.

IVIg should be used for three to six months (three to six courses) before determining whether the patient has responded. Most individuals will respond within three months unless there is significant axonal degeneration whereby a six-month course will be necessary. If there is no benefit after three to six courses, IVIg therapy should be abandoned.

Review

Regular review by neurologist is required: frequency as determined by clinical status of patient.

For stable patients on maintenance treatment, review by a neurologist is required at least annually.

Effectiveness

Clinical documentation of effectiveness is necessary for continuation of IVIg therapy.

Effectiveness can be demonstrated by objective findings of either:

1. Improvement in functional scores activities of daily living (ADL) or quantitative muscle scores or Medical Research Council (MRC) muscle assessment or neuropathy score;

OR

2. Stabilisation of disease as defined by stable functional scores (ADLs) or quantitative muscle scores or MRC muscle assessment or neuropathy score after previous evidence of deterioration in one of these scores.

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

Maintenance: 0.4–2 g/kg, 2–6 weekly. The amount per dose should be titrated to the individual’s response.

Aim for the minimum dose to maintain optimal functional status.

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.

Short-term therapy in patients with clinically definite relapsing remitting MS in the following circumstances:

1. Pregnancy and the immediate post-partum period when other immunomodulation is contraindicated;
2. Young patients with severe relapsing remitting disease in whom other therapies have failed;
3. Severe relapse with no response to high-dose methylprednisolone.

Evidence of probable benefit (Category 2a).

MS is a chronic disorder of the central nervous system (CNS) characterised by a triad of inflammation, demyelination and gliosis. Lesions of MS, known as plaques, are typically disseminated in time and location throughout the brain and spinal cord.

Four clinical types of MS have been described: relapsing/remitting MS (RRMS), primary progressive MS (PPMS), secondary progressive MS (SPMS), and progressive/relapsing MS (PRMS).

Diagnosis requires two or more episodes of symptoms and two or more signs that reflect pathology in anatomically non-contiguous white matter tracts of the CNS. Symptoms must last >24 hours and occur as separate episodes at least one month apart. At least one of the two signs must be present on neurological examination, while the other may be detected by paraclinical tests such as intrathecal IgG (oligoclonal bands and visual evoked potentials).

Clinically definite RRMS as defined by McDonald et al (2001) criteria and confirmed by a neurologist with one of the following indications:

1. Pregnancy and immediate post partum period when other immunomodulation is contraindicated;

OR

2. Young patients with severe relapsing remitting disease in whom other therapies have failed;

OR

3. Severe relapse with no response to high-dose methylprednisolone.

Application for IVIg use for these indications will be considered on a case-by-case basis and may be reviewed by an expert neurologist in MS in each state.

Note: There are numerous immunomodulatory therapies available for multiple sclerosis. IVIg is not available for routine ongoing treatment for patients with MS.

1. Primary progressive MS.
2. Progressive phase of MS without relapses.

• Six-monthly review by a neurologist is required.
• Objective evidence of improvement in relapse rate in comparison to pre-treatment levels.
• Other measures that may be useful include:
  • expanded disability status scale;
  • MS functional scores;
  • other functional measures.

Induction: 1–2 g/kg in 2 to 5 divided doses.

Maintenance dose for indications 1 and 2 above: 0.4–1 g/kg, 4–6 weekly.

Aim for minimum dose to maintain optimal functional status.

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. As an alternative treatment to plasma exchange in acute exacerbation (myasthenic crisis) or before surgery and/ or thymectomy.
2. As maintenance therapy for moderate to severe Mg when other treatments have been ineffective or caused intolerable side effects.

Clear evidence of benefit (Category 1)

MG is an autoimmune disease associated with the presence of antibodies to acetylcholine receptors (AChR) or to muscle-specific tyrosine kinase (MuSK) at the neuromuscular junction. Some patients with myasthenia gravis are antibody negative.

Clinical features are characterised by fluctuating weakness and fatigability of voluntary muscles, namely levator palpebrae, extraocular, bulbar, limb and respiratory muscles. Patients usually present with unilateral or bilateral drooping of eyelid (ptosis), double vision (diplopia), difficulty in swallowing (dysphagia) and proximal muscle weakness. Weakness of respiratory muscles can result in respiratory failure in severe cases or in acute severe exacerbations (myasthenic crisis).

Diagnosis is suspected based on the clinical picture described above, without loss of reflexes or impairment of sensation. repetitive nerve stimulation typically shows a decreasing response at 2–3 Hz, which repairs after brief exercise (exercise facilitation). Edrophonium can be used for confirmation. Other useful investigations include serum anti-AChR or MuSK antibody titre, or SFEMG (single-fibre electromyography).

Mandatory diagnosis and assessment by a neurologist;

AND

1. As an alternative treatment to plasma exchange in acute exacerbation (myasthenic crisis) or before surgery and/ or thymectomy;

OR

2. As maintenance therapy for moderate to severe Mg when other treatments have been ineffective or caused intolerable side effects.

IVIg should be used for three to six months (three to six courses) before determining whether the patient has responded. If there is no benefit after three to six courses, IVIg therapy should be abandoned.

Review

Regular review by neurologist is required: frequency as determined by clinical status of patient. Initial review three to six monthly.

For stable patients on maintenance treatment, review by a neurologist is required at least annually.

Effectiveness

Clinical documentation of effectiveness is necessary for continuation of IVIg therapy.

Effectiveness can be demonstrated by improvement in fatigability and weakness.

Various scores can be used, including:

• forward arm abduction time (up to a full five minutes);
• Quantitative Myasthenia gravis score (Duke);
• respiratory function (e.g. forced vital capacity);
• quantitative dynamometry of proximal limb muscles;
• variation of a myasthenic muscular score (MSS).

Maintenance: 0.4–1 g/kg, 4–6 weekly.

Induction or before surgery, or during myasthenic crisis: 1–2 g/kg in 2 to 5 divided doses.

Aim for minimum dose to maintain optimal functional status.

Note: smaller dosage may be of greater efficacy.

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.

There is some evidence that IVIg improves cardiac function in children with proven or likely viral myocarditis.

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)