| Specific Conditions |
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| Indication for Ig Use |
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| Level of Evidence | Evidence of probable benefit – more research needed (Category 2a) |
| Description and Diagnostic Criteria |
Multiple sclerosis (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). New evidence and consensus in 2010 have led to further revision of the McDonald criteria for the diagnosis of MS. The use of imaging for demonstration of dissemination of CNS lesions in space and time is defined. The 2010 revisions simplify the diagnostic criteria, maintain their diagnostic sensitivity and specificity and support earlier diagnosis and more uniform and widespread use (Polman et al, 2011). |
| Justification for Evidence Category | While literature and systematic reviews in 2004 and 2006 demonstrate probable benefit, there are a broad range of licenced therapeutics now available to treat MS and in particular, RRMS, with evidence supported by large randomised controlled trials. Such evidence indicates that intravenous immunoglobulin (IVIg) use in MS should be limited to exceptional circumstances only and there is no longer a role for IVIg in the continuing treatment of MS. IVIg may be indicated in treatment of relapses where there are severe disabling consequences of the attack (e.g. paraparesis or blindness). For more information refer to 'Therapeutic approaches to disease modifying therapy for multiple sclerosis in adults: an Australian and New Zealand perspective: part 3 treatment practicalities and recommendations' (Broadley et al, 2014). |
| Diagnosis Requirements |
A diagnosis must be made by a Neurologist. |
| Qualifying Criteria for Ig Therapy |
Severe relapse of clinically definite relapsing remitting multiple sclerosis (RRMS) with no response to high dose methylprednisolone or where methylprednisolone is contraindicated
AND
Prevention of relapse of clinically definite relapsing remitting multiple sclerosis (RRMS) where alternative therapies are inappropriate, unavailable or contraindicated
Review by a neurologist is required every six months. Documentation of clinical effectiveness is necessary for continuation of IVIg therapy. Effectiveness can be demonstrated by objective findings of improvement in relapse rate in comparison to pre-treatment levels. After a maximum of 12 months treatment, patients should be re-assessed as to whether a more appropriate treatment is available. A new authorisation request will be required for any subsequent course (after 12 months) as appropriate. |
| Exclusion Criteria |
Primary progressive MS Progressive phase of MS without relapses |
| Review Criteria for Assessing the Effectiveness of Ig Use |
Severe relapse of clinically definite relapsing remitting multiple sclerosis (RRMS) with no response to high dose methylprednisolone or where methylprednisolone is contraindicated
Review is not mandated for this indication however the following criteria may be useful in assessing the effectiveness of Ig therapy
Prevention of relapse of clinically definite relapsing remitting multiple sclerosis (RRMS) where alternative therapies are inappropriate, unavailable or contraindicated
Review by a neurologist is required every 6 months. Documentation of clinical effectiveness is necessary for continuation of IVIg therapy. Effectiveness can be demonstrated by objective findings of improvement in relapse rate in comparison to pre-treatment levels. After a maximum of 12 months treatment, patients should be re-assessed as to whether a more appropriate treatment is available. A new authorisation request will be required for any subsequent course (after 12 months) as appropriate. Clinical effectiveness of Ig therapy may be demonstrated by:
|
| Dose |
Severe relapse of clinically definite relapsing remitting multiple sclerosis (RRMS) with no response to high dose methylprednisolone or where methylprednisolone is contraindicated
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 contraindication. Note: There are numerous immunomodulatory therapies available for multiple sclerosis. IVIg is not available for routine ongoing treatment for patients with MS. Prevention of relapse of clinically definite relapsing remitting multiple sclerosis (RRMS) where alternative therapies are inappropriate, unavailable or contraindicated
After a maximum of 12 months treatment, patients should be re-assessed as to whether a more appropriate treatment is available. A new authorisation request will be required for any subsequent course (after 12 months) as appropriate.
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. Note: There are numerous immunomodulatory therapies available for multiple sclerosis. IVIg is not available for routine ongoing treatment for patients with MS. Patients should be re-assessed as to whether more appropriate treatment is available. |
| Bibliography |
|---|
Achiron A, Kishner I, Sarova-Pinhas I et al (2004) ‘Intravenous immunoglobulin treatment following the first demyelinating event suggestive of multiple sclerosis: a randomized, double-blind, placebo-controlled trial’, Archives of Neurology, 61(10):1515–20, DOI: 10.1001/archneur.61.10.1515. Association of British Neurologists (2005) ‘Guidelines for the use of intravenous immunoglobulin in neurological diseases’, The Association, London. Barak Y, Gabbay U, Gilad R et al (1999) ‘Neuropsychiatric assessment as a secondary outcome measure in a multiple sclerosis intravenous immunoglobulin trial’, International Journal of Psychiatry in Clinical Practice, 3(1):31–4, DOI: 10.3109/13651509909024756. Broadley SA, Barnett MH, Boggild M et al (2014) ‘Therapeutic approaches to disease modifying therapy for multiple sclerosis in adults: an Australian and New Zealand perspective: part 3 treatment practicalities and recommendations. MS Neurology Group of the Australian and New Zealand Association of Neurologists’, Journal of clinical neuroscience, 21(11):1857-65, DOI: 10.1016/j.jocn.2014.01.017. Deisenhammer F, Fazekas F, Strasser-Fuchs S et al (1999) ‘Intravenous immunoglobulins in multiple sclerosis: results of the Austrian Immunoglobulin in Multiple Sclerosis (AIMS) trial’, Infusionstherapie und Transfusionsmedizin, 26(suppl 2):42–7, DOI: 10.1159/000053538. Fazekas F, Sorensen PS, Filippi M et al (2005) ‘MRI results from the European Study on Intravenous Immunoglobulin in Secondary Progressive Multiple Sclerosis (ESIMS)’, Multiple Sclerosis, 11(4):433–40, DOI: 10.1191/1352458505ms1196oa. Filippi M, Rocca MA, Pagani E et al (2004) ‘European study on intravenous immunoglobulin in multiple sclerosis: results of magnetization transfer magnetic resonance imaging analysis’, Archives of Neurology, 61(9):1409–12, DOI: 10.1001/archneur.61.9.1409. Goodin DS, Frohman EM, Garmany GP et al (2002) ‘Disease modifying therapies in multiple sclerosis: Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines’, Neurology, 58(2):169–78, DOI: 10.1212/wnl.58.2.169. Gray OM, McDonnell GV & Forbes RB (2003) ‘Intravenous immunoglobulins for multiple sclerosis’, Cochrane Database of Systematic Reviews, 2003(4):CD002936, DOI: 10.1002/14651858.CD002936. Kurtzke JF (1983) ‘Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS)’, Neurology, 33(11):1444-52, DOI: 10.1212/wnl.33.11.1444. Lewanska M, Siger-Zajdel M & Selmaj K (2002) ‘No difference in efficacy of two different doses of intravenous immunoglobulins in MS: clinical and MRI assessment’, European Journal of Neurology, 9(6):565–72, DOI: 10.1046/j.1468-1331.2002.00500.x. McDonald WI, Compston A, Edan G et al (2001) ‘Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis’, Annals of Neurology, 50(1):121–7, DOI: 10.1002/ana.1032. Multiple Sclerosis Trust (2017) ‘Expanded Disability Status Scale (EDSS)’, Available from: https://www.mstrust.org.uk/a-z/expanded-disability-status-scale-edss. Noseworthy JH, O’Brien PC, Weinshenker BG et al (2000) ‘IV immunoglobulin does not reverse established weakness in MS’, Neurology, 55(8):1135–43, DOI: 10.1212/WNL.55.8.1135. Orange JS, Hossny EM, Weiler CR et al (2006) ‘Use of intravenous immunoglobulin in human disease: A review of primary evidence by members of the Primary Immunodeficiency Committee of the American Academy of Allergy, Asthma and Immunology’, Journal of Allergy and Clinical Immunology, 117(4):S525–53, DOI: 10.1016/j.jaci.2006.01.015. Oztekin N & Oztekin MF (1998) ‘Intravenous immunoglobulin treatment in relapsing-remitting multiple sclerosis: a double blind cross over study’, Multiple Sclerosis, 4(4):391, https://www.researchgate.net/publication/258422554_Intravenous_immunoglobulin_treatment_in_chronic_inflammatory_polyneuropathy_and_multifocal_motor_neuropathy. Polman CH, Reingold SC, Banwell B et al (2011) ‘Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria’, Annals of neurology, 69(2):292-302, DOI: 10.1002/ana.22366. DOI: 10.1002/ana.22366. Sacher RA & IVIg Advisory Panel (2001) ‘Intravenous immunoglobulin consensus statement’, Journal of Allergy and Clinical Immunology, 108(4):S139–46, DOI: 10.1067/mai.2001.118640. Soelberg-Sorensen P, Haas J, Sellebjerg F et al (2004) ‘IV immunoglobulins as add-on treatment to methylprednisolone for acute relapses in MS’, Neurology, 63(11):2028–33, DOI: 10.1212/01.wnl.0000145798.61383.39. Soelberg-Sorensen P, Wanscher B, Schreiber K et al (1997) ‘A double-blind, cross-over trial of intravenous immunoglobulin G in multiple sclerosis: Preliminary results’, Multiple Sclerosis, 3(2):145-148, DOI: 10.1177/135245859700300216. Sorensen PS, Fazekas, F & Lee, M (2002) ‘Intravenous immunoglobulin G for the treatment of relapsing-remitting multiple sclerosis: a meta-analysis’, European Journal of Neurology, 9(6):557–63, DOI: 10.1046/j.1468-1331.2002.00501. Stangel M, Boegner F, Klatt CH et al (2000) ‘Placebo controlled pilot trial to study the remyelinating potential of intravenous immunoglobulins in multiple sclerosis’, Journal of Neurology, Neurosurgery and Psychiatry, 68(1):89–92, DOI: 10.1136/jnnp.68.1.89. Strasser-Fuchs S, Fazekas F, Deisenhammer F et al (2000) ‘The Austrian Immunoglobulin in MS (AIMS) study: final analysis’, Multiple Sclerosis, 6(2):S9–13, https://www.ncbi.nlm.nih.gov/pubmed/11188778. Visser LH, Beekman R, Tijssen CC et al (2004) ‘A randomized, double-blind, placebo-controlled pilot study of i.v. immune globulins in combination with IV methylprednisolone in the treatment of relapses in patients with MS’, Multiple Sclerosis, 10(1):89–91, DOI: 10.1191/1352458504ms978sr. |