| Specific Conditions |
|
| Indication for Ig Use |
|
| 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 has led to further revision of the McDonald Criteria for diagnosis of multiple sclerosis. The use of imaging for demonstration of dissemination of central nervous system 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 multiple sclerosis (MS) and in particular, relapsing/remitting MS (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 see: Therapeutic approaches to disease modifying therapy for multiple sclerosis in adults: an Australian and New Zealand perspective: part 3 treatment practicalities and recommendations Journal of Clinical Neuroscience 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
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 avaialble. 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 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. 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, vol. 61, no.10, pp.1515–20 https://www.ncbi.nlm.nih.gov/pubmed/15477504 Association of British Neurologists 2005, Guidelines for the use of intravenous immunoglobulin in neurological diseases, The Association, London. Available from: www.theabn.org/abn/ userfiles/file/IVIg-guidelines-final-July05.pdf 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, vol.3, no.1, pp.31–4. https://www.tandfonline.com/doi/abs/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 : official journal of the Neurosurgical Society of Australasia, vol. 21, no. 11, pp. 1857-65. https://www.ncbi.nlm.nih.gov/pubmed/24993136 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, vol. 26, pp. 42–7. https://www.karger.com/Article/Abstract/53538 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, vol. 11, no. 4, pp. 433–40. https://www.ncbi.nlm.nih.gov/pubmed/16042226 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, vol. 61, no. 9, pp. 1409–12. https://www.ncbi.nlm.nih.gov/pubmed/15364687 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, vol. 58, no. 2, pp. 169–78. https://www.ncbi.nlm.nih.gov/pubmed/11805241 Gray, OM, McDonnell, GV & Forbes, RB 2003, ‘Intravenous immunoglobulins for multiple sclerosis, (Cochrane Review)’, in The Cochrane Library, Issue 42, John Wiley & Sons, Ltd, Chichester, UK. https://www.ncbi.nlm.nih.gov/pubmed/14583956 Kurtzke, JF 1983, ‘Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS)’, Neurology, , vol. 33, no. 11, pp. 1444-52. https://www.ncbi.nlm.nih.gov/pubmed/6685237 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, vol. 9, no. 6, pp. 565–72. https://onlinelibrary.wiley.com/doi/pdf/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, vol. 50, no. 1, pp. 121–7. https://www.ncbi.nlm.nih.gov/pubmed/11456302 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, vol. 55, no. 8, pp. 1135–43. http://n.neurology.org/content/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, vol. 117, no. 4, pp. S525–53. https://www.ncbi.nlm.nih.gov/pubmed/16580469 Oztekin, N & Oztekin MF 1998, ‘Intravenous immunoglobulin treatment in relapsing-remitting multiple sclerosis: a double blind cross over study’, Multiple Sclerosis, vol. 4, p. 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, vol. 69, no. 2, pp. 292-302. https://www.ncbi.nlm.nih.gov/pubmed/21387374 Roed, HG, Langkilde, A, Sellebjerg, F, et al 2005, ‘A double-blind randomised trial of IV immunoglobulin treatment in acute optic neuritis’, Neurology, vol. 64, pp. 804–10. https://www.ncbi.nlm.nih.gov/pubmed/15753413 Sacher, RA & IVIg Advisory Panel 2001, ‘Intravenous immunoglobulin consensus statement’, Journal of Allergy and Clinical Immunology, vol. 108, no. 4, pp. S139–46. https://www.ncbi.nlm.nih.gov/pubmed/11586282 Soelberg-Sorensen, P, Haas, J, Sellebjerg, F, et al 2004, ‘IV immunoglobulins as add-on treatment to methylprednisolone for acute relapses in MS’, Neurology, vol. 63, no. 11, pp. 2028–33. https://www.ncbi.nlm.nih.gov/pubmed/15596745 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 Journal , vol. 3, issue 2, p. 145-148. http://journals.sagepub.com/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, vol. 9, no. 6, pp. 557–63. https://pdfs.semanticscholar.org/91e5/6b5375480d9197cb28626c6a9b02bb03b1aa.pdf 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, vol. 68, no. 1, pp. 89–92. https://www.ncbi.nlm.nih.gov/pubmed/10601410 Strasser-Fuchs, S, Fazekas, F, Deisenhammer, F, et al 2000, ‘The Austrian Immunoglobulin in MS (AIMS) study: final analysis’, Multiple Sclerosis, vol. 6, suppl. 2, pp. 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, vol. 10, no. 1, pp. 89–91. https://www.ncbi.nlm.nih.gov/pubmed/14760960 |