This medical condition has either been superseded or has become inactive
Specific Conditions |
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Indication for Ig Use |
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Level of Evidence | Clear evidence of benefit (Category 1) |
Description and Diagnostic Criteria |
Myasthenia gravis (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 single-fibre electromyography (SFEMG). |
Justification for Evidence Category |
The Cochrane review of seven randomised controlled trials (RCTs) (Gajdos et al 2012) found:
There is insufficient placebo-controlled evidence for the use of IVIg as a steroid-sparing agent or before thymectomy in stable MG, although multiple case reports suggest benefit in this context. Kernstine (2005) suggested that preoperative preparation with plasma exchange (PLEX) or IVIg should be considered for patients with advanced disease, bulbar symptoms, or poor pulmonary function. The corollary is that treatment is generally not required for patients without those features. Effectiveness of IVIg is equivalent to PLEX, but IVIg may be easier to administer than PLEX, which is also not available in some centres. The differing risks of these treatments should also be taken into account, including IV line insertion risks, line sepsis and haemodynamic effects for PLEX, and inflammatory and thrombotic consequences of IVIg. Several other important series have been published noting these were non-randomised and retrospective: Guptill (2011) published that PLEX is more effective than IVIg in MuSK antibody associated MG and this accords with other groups. Hellman (2014) published that IVIg, while improving MG with chronic use, does not induce remission or alter the natural history of the disease. Therefore, the Specialist Working Group suggests IVIg should be regarded as a stopgap while using short-term drugs such as pyridostigmine and while introducing effective immunotherapy. The Quantitative MG Score (QMGS) (Bedlack 2005) has been the rating scale most commonly used in MG trials, and a score of greater than 11 has been shown to be a predictor of response to IVIg or PLEX (Katzberg 2012). However, the QMGS is a labour-intensive scale for trial use, and for clinical use the abbreviated MG Composite score (MGCS) has been recommended. This composite includes only items routinely examined and key patient reported symptoms (Burns 2010). An improvement of greater than or equal to three on the MGCS has been shown to have clinical significance. A lowest score predictive of response to IVIG has not been established for the MGCS to date. |
Diagnosis Requirements |
A diagnosis must be made by a Neurologist. |
Qualifying Criteria for Ig Therapy |
Myasthenic crisis as an alternative treatment to plasma exchange
AND
MG prior to surgery and/or thymectomy in patients with advanced disease, bulbar symptoms or respiratory involvement, as an alternative treatment to plasma exchange
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As maintenance therapy for moderate to severe MG when other treatments have been ineffective or caused intolerable side effects
IVIg should be used for four months (induction plus three maintenance cycles) before determining whether the patient has responded. If there is no benefit after this treatment, IVIg therapy should be abandoned. Review by a neurologist is required within four months and annually thereafter. Documentation of clinical effectiveness is necessary for continuation of IVIg therapy. |
Exclusion Criteria |
Pure Ocular Myasthenia Gravis |
Review Criteria for Assessing the Effectiveness of Ig Use |
Myasthenic crisis as an alternative treatment to plasma exchange
Review is not mandated for this indication however the following criteria may be useful in assessing the effectiveness of Ig therapy.
MG prior to surgery and/or thymectomy in patients with advanced disease, bulbar symptoms or respiratory involvement, as an alternative treatment to plasma exchange
Review is not mandated for this indication however clinical effectiveness of Ig therapy may be assessed by:
As maintenance therapy for moderate to severe MG when other treatments have been ineffective or caused intolerable side effects
IVIg should be regarded as a stopgap treatment while using short-term drugs such as pyridostigmine and while introducing effective immunotherapy.
IVIg should be used for four months (induction plus three maintenance cycles) before determining whether the patient has responded. If there is no benefit after this treatment, IVIg therapy should be abandoned. Review by a neurologist is required within four months and annually thereafter. Documentation of clinical effectiveness is necessary for continuation of IVIg therapy. Clinical effectiveness of Ig therapy may be assessed by: On review of the initial authorisation period
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On review of a continuing authorisation period
AND
AND
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Dose |
Myasthenic crisis as an alternative treatment to plasma exchange
The aim should be to use the lowest dose possible that achieves the appropriate clinical outcome for each patient.
Refer to the current product information sheet for further information on dose, administration and contraindications. MG prior to surgery and/or thymectomy in patients with advanced disease, bulbar symptoms or respiratory involvement, as an alternative treatment to plasma exchange
The aim should be to use the lowest dose possible that achieves the appropriate clinical outcome for each patient.
Refer to the current product information sheet for further information on dose, administration and contraindications. As maintenance therapy for moderate to severe MG when other treatments have been ineffective or caused intolerable side effects
The aim should be to use the lowest dose possible that achieves the appropriate clinical outcome for each patient.
Refer to the current product information sheet for further information on dose, administration and contraindications. |
Bibliography |
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Bedlack, RS, Simel, DL, Bosworth, H, et al 2005, ‘Quantitative myasthenia gravis score: assessment of responsiveness and longitudinal validity’, Neurology., vol. 64, no. 11, pp. 1968-70. https://www.ncbi.nlm.nih.gov/pubmed/15955957 Biotext 2004, ‘Summary data on conditions and paper’, in A systematic literature review and report on the efficacy of intravenous immunoglobulin therapy and its risks, commissioned by the National Blood Authority on behalf of all Australian Governments, pp. 188–9. Available from: https://www.blood.gov.au/system/files/A-systematic-literature-review-and-report-on-the-efficacy-of-IVIg-therapy-and-its-risks.pdf Burns, TM, Conaway, MR, Cutter, GR, et al 2008, ‘Construction of an efficient evaluative instrument for myasthenia gravis: The MG composite’, Muscle Nerve, vol. 38, no. 6, pp. 1553–62. Burns, TM, Conaway, M, Sanders, DB, et al 2010, ‘The MG composite: A valid and reliable outcome measure for myasthenia gravis’, Neurology, vol. 74, no 18, pp. 1434–40. https://www.ncbi.nlm.nih.gov/pubmed/20439845 Darabi, K, Abdel-Wahab, O & Dzik WH 2006, ‘Current usage of intravenous immunoglobulin and the rationale behind it: the Massachusetts General Hospital data and review of the literature’, Transfusion, vol. 46, no. 5, pp. 741–53. https://www.ncbi.nlm.nih.gov/pubmed/16686841 Gajdos, P, Chevret, S & Toyka, K 2003, ‘Intravenous immunoglobulin for myasthenia gravis’, Cochrane Database of Systematic Reviews 2012, Issue 12. Art. No.: CD002277. DOI: 10.1002/14651858.CD002277.pub4. Gajdos P, Tranchant C, Clair B, et al 2005, ‘Treatment of myasthenia gravis exacerbation with intravenous immunoglobulin: a randomized double-blind clinical trial’, Archives of neurology, vol. 62, no. 11, pp. 1689-93. https://www.ncbi.nlm.nih.gov/pubmed/16286541 Guptill, JT, Sanders, DB & Evoli, A 2011, 'Anti-MuSK antibody myasthenia gravis: clinical findings and response to treatment in two large cohorts’, Muscle Nerve, vol. 44, no. 1, pp. 36-40. https://www.ncbi.nlm.nih.gov/pubmed/21674519 Hellmann, MA, Mosberg-Galili, R, Lotan, I, et al 2014, ‘Maintenance IVIg therapy in myasthenia gravis does not affect disease activity’, Journal of the neurological sciences, vol. 338, issues 1-2, pp. 39-42. https://www.jns-journal.com/article/S0022-510X(13)03005-0/pdf Katzberg, HD, Barnett, C, & Bril, V 2012, ‘Predictors of response to immunomodulation in patients with myasthenia gravis’, Muscle Nerve, vol. 45, no. 5, pp. 648-52. https://www.ncbi.nlm.nih.gov/pubmed/22499090. Kernstine KH 2005, ‘Preoperative preparation of the patient with myasthenia gravis’, Thoracic surgery clinics, vol. 15, no. 2, pp. 287-95. https://www.ncbi.nlm.nih.gov/pubmed/15999526 Kornberg, AJ, for the Asia–Pacific IVIg Advisory Board 2004, Bringing consensus to the use of IVIg in neurology. Expert consensus statements on the use of IVIg in neurology, 1st edn, Asia–Pacific IVIg Advisory Board, Melbourne. Muppidi, S, Wolfe, GI, Conaway, M, et al 2011, ‘MG-ADL: Still a relevant outcome measure, Muscle & Nerve, vol. 44, no. 5, pp. 727–31. https://www.ncbi.nlm.nih.gov/pubmed/22006686 |