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Early Treatment in Multiple Sclerosis with Intravenous Immunoglobulin: Rationale and Study Design

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Part of the book series: Topics in Neuroscience ((TOPNEURO))

Abstract

Multiple sclerosis (MS) is a chronic debilitating disease that will cause significant disability to the majority of patients overtime [1]. Previous studies of the natural course of the disease showed that disability will accumulate in more that 90% of patients and additional relapses may result in significant handicap [2]. Assessment of patients with a diagnosis of probable MS with positive brain magnetic resonance imaging (MRI) demonstrated that the risk of relapsing within 1 year is 57.6% [3]. Treating patients early means treating patients with less disability. We describe the rationale for early treatment in patients with the first episode of neurological symptomatology suggestive of clinically probable MS, and the design of a randomized, double-blind, placebo-controlled trial of early treatment with intravenous immunoglobulin (IVIg, Omrix, Israel) in these patients. The primary objective of this study was to investigate the efficacy of IVIg treatment, administered at 0.4 g/kg per day for 5 consecutive days, as a loading dose, and 0.4 g/kg per day every 6 weeks thereafter as a booster dose, for a 1-year period, on the risk of patients with clinically probable MS and positive brain MRI to convert to clinically definite MS.

“… as the physicians say it happens in hectic fever, that in the beginning of the malady it is easy to cure but difficult to detect, but in the course of time, not having been either detected or treated in the beginning, it becomes easy to detect but difficult to cure.”

Niccolò Machiavelli, The Prince (1640)

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References

  1. Weinshenker BG (1994) Natural history of multiple sclerosis. Ann Neurol 36 [Suppl]: S6–S11

    Article  PubMed  Google Scholar 

  2. Amato MP, Ponziani G, Bartolozzi ML, Siracusa G (1999) A prospective study on the natural history of multiple sclerosis: clues to the conduct and interpretation of clinical trials. J Neurol Sci 168:96–106

    Article  PubMed  CAS  Google Scholar 

  3. Achiron A, Barak Y (2000) Multiple sclerosis — from probable to definite diagnosis: a prospective study over 7 years. Arch Neurol 57:974–979

    Article  PubMed  CAS  Google Scholar 

  4. Lublin FD, Whitaker JN, Eidelman BH, Miller AE, Arnason BG, Burks JS (1996) Management of patients receiving interferon beta-lb for multiple sclerosis: report of a consensus conference. Neurology 46:12–18

    Article  PubMed  CAS  Google Scholar 

  5. Simon JH, Jacobs LD, Campion M, Wende K, Simonian N, Cookfair DL et al (1998) Magnetic resonance studies of intramuscular interferon beta-1a for relapsing multiple sclerosis. The Multiple Sclerosis Collaborative Research Group. Ann Neurol 43:79–87

    Article  PubMed  CAS  Google Scholar 

  6. Wolinsky JS (1995) Copolymer 1: a most reasonable alternative therapy for early relapsing-remitting multiple sclerosis with mild disability. Neurology 45:1245–1247

    Article  PubMed  CAS  Google Scholar 

  7. Achiron A, Gabbay U, Gilad R, Hassin-Baer S, Barak Y, Gornish M, Elizur A, Goldhammer Y, Sarova-Pinhas I (1998) Intravenous immunoglobulin treatment in multiple sclerosis: effect on relapses. Neurology 50:398–402

    Article  PubMed  CAS  Google Scholar 

  8. Miller A (1998) Diagnosis of multiple sclerosis. Semin Neurol 18:309–316

    Article  PubMed  CAS  Google Scholar 

  9. Bourdette D, Antel J, McFarland H, Montgomery E (1999) Monitoring relapsing remitting MS patients. J Neuroimmunol 98:16–21

    Article  PubMed  CAS  Google Scholar 

  10. Thompson AJ, Noseworthy JH (1996) New treatments for multiple sclerosis: a clinical perspective. Curr Opin Neurol 9:187–198

    Article  PubMed  CAS  Google Scholar 

  11. Trials ECFWGfT (1995) Guidelines for early treatment trials in patients presenting with clinical and paraclinical abnormalities which put them at high risk for conversion to multiple sclerosis. European Charcot Foundation Working Group for Treatment Trials. Mult Scler 1 [Suppl 1]:S55–S59

    Google Scholar 

  12. Comi G, Barkhof F, Durelli L, Edan G, Fernandez O, Filippi M, Hartung HP, Hommes OR, Seeldrayers P, Soelberg-Sorensen P (1995) Early treatment of multiple sclerosis with Rebif (recombinant human interferon beta): design of the study. Mult Scler 1 [Suppl 1]:S24–S27

    PubMed  CAS  Google Scholar 

  13. Munschauer FE, Stuart WH (1997) Rationale for early treatment with interferon beta-la in relapsing-remitting multiple sclerosis. Clin Ther 19:868–882

    Article  PubMed  Google Scholar 

  14. Rudick RA, Goodman A, Herndon RM, Panitch HS (1999) Selecting relapsing remitting multiple sclerosis patients for treatment: the case for early treatment. J Neuroimmunol 98:22–28

    Article  PubMed  CAS  Google Scholar 

  15. Jacobs LD, Beck RW, Simon JH, Kinkel RP, Brownscheidle CM, Murray TJ, Simonian NA, Slasor PJ, Sandrock AW (2000) Intramuscular interferon beta-la therapy initiated during a first demyelinating event in multiple sclerosis. CHAMPS Study Group. N Engl J Med 343:898–904

    Article  PubMed  CAS  Google Scholar 

  16. Comi G, Filippi M, Barkhof F, Durelli L, Edan G, Fernandez O, Hartung H, Seeldrayers P, Sorensen PS, Rovaris M, Martinelli V, Hommes OR (2001) Effect ofearly interferon treatment on conversion to definite multiple sclerosis: a randomised study. Lancet 357:1576–1582

    Article  PubMed  CAS  Google Scholar 

  17. Vanderlugt CL, Neville KL, Nikcevich KM, Eagar TN, Bluestone JA, Miller SD (2000) Pathologic role and temporal appearance of newly emerging autoepitopes in relapsing experimental autoimmune encephalomyelitis. J Immunol 164:670–678

    PubMed  CAS  Google Scholar 

  18. Miller SD, McRae BL, Vanderlugt CL, Nikcevich KM, Pope JG, Pope L, Karpus WI (1995) Evolution of the T-cell repertoire during the course of experimental immune-mediated demyelinating diseases. Immunol Rev 144:225–244

    Article  PubMed  CAS  Google Scholar 

  19. Tuohy VK, Yu M, Yin L, Kawczak JA, Kinkel RP (1999) Spontaneous regression of primary autoreactivity during chronic progression of experimental autoimmune encephalomyelitis and multiple sclerosis. J Exp Med 189:1033–1042

    Article  PubMed  CAS  Google Scholar 

  20. Barkhof F, van Walderveen M (1999) Characterization of tissue damage in multiple sclerosis by nuclear magnetic resonance. Philos Trans R Soc Lond B Biol Sci 354:1675–1686

    Article  PubMed  CAS  Google Scholar 

  21. Matthews PM, De Stefano N, Narayanan S, Francis GS, Wolinsky JS, Antel JP, Arnold DL (1998) Putting magnetic resonance spectroscopy studies in context: axonal damage and disability in multiple sclerosis. Semin Neurol 18:327–336

    Article  PubMed  CAS  Google Scholar 

  22. Miller DH, Grossman RI, Reingold SC, McFarland HF (1998) The role of magnetic resonance techniques in understanding and managing multiple sclerosis. Brain 121:3–1224

    Article  PubMed  Google Scholar 

  23. Davie CA, Silver NC, Barker GJ, Tofts PS, Thompson AJ, McDonald WI, Miller DH (1999) Does the extent of axonal loss and demyelination from chronic lesions in multiple sclerosis correlate with the clinical subgroup? J Neurol Neurosurg Psychiatry 67:710–715

    Article  PubMed  CAS  Google Scholar 

  24. Rudick RA, Fisher E, Lee JC, Simon J, Jacobs L (1999) Use of the brain parenchymal fraction to measure whole brain atrophy in relapsing-remitting MS. Multiple Sclerosis Collaborative Research Group. Neurology 53:1698–1704

    Article  PubMed  CAS  Google Scholar 

  25. Zivadinov R, Sepcic J, Nasuelli D, De Masi R, Bragadin LM, Tommasi MA, Zambito-Marsala S, Moretti R, Bratina A, Ukmar M, Pozzi-Mucelli RS, Grop A, Cazzato G, Zorzon M (2001) A longitudinal study of brain atrophy and cognitive disturbances in the early phase of relapsing-remitting multiple sclerosis. J Neurol Neurosurg Psychiatry 70:773–780

    Article  PubMed  CAS  Google Scholar 

  26. Achiron A, Barak Y (2003) Cognitive impairment in probable multiple sclerosis. J Neurol Neurosurg Psychiatry 74:443–446

    Article  PubMed  CAS  Google Scholar 

  27. Lassmann H, Bruck W, Lucchinetti C, Rodriguez M (1997) Remyelination in multiple sclerosis. Mult Scler 3:133–136

    Article  PubMed  CAS  Google Scholar 

  28. Trapp BD, Peterson J, Ransohoff RM, Rudick R, Mork S, Bo L (1998) Axonal transection in the lesions of multiple sclerosis. N Engl I Med 339:278–285

    Article  Google Scholar 

  29. Trapp BD, Bo L, Mork S, Chang A (1999) Pathogenesis of tissue injury in MS lesions. J Neuroimmunol 98:49–56

    Article  PubMed  CAS  Google Scholar 

  30. Fazekas F, Deisenhammer F, Strasser-Fuchs S, Nahler G, Mamoli B (1997) Randomised placebo-controlled trial of monthly intravenous immunoglobulin therapy in relapsing-remitting multiple sclerosis. Austrian Immunoglobulin in Multiple Sclerosis Study Group. Lancet 349:589–593

    Article  PubMed  CAS  Google Scholar 

  31. Sorensen PS, Wanscher B, Jensen CV, Schreiber K, Blinkenberg M, Ravnborg M, Kirsmeier H, Larsen VA, Lee ML (1998) Intravenous immunoglobulin G reduces MRI activity in relapsing multiple sclerosis. Neurology 50:1273

    Article  PubMed  CAS  Google Scholar 

  32. Achiron A, Gabbay U, Gilad R, Hassin-Baer S, Barak Y, Gornish M, Elizur A, Goldhammer Y, Sarova-Pinhas I (1998) Intravenous immunoglobulin treatment in multiple sclerosis: effect on relapses. Neurology 50:398–402

    Article  PubMed  CAS  Google Scholar 

  33. Achiron A (1997) Complications of intravenous immune globulin treatment in neurologic disease. Neurology 49:899–900

    Article  PubMed  CAS  Google Scholar 

  34. Achiron A, Rotstein Z, Noy S, Mashiach S, Dulitzky M, Achiron R (1996) Intravenous immunoglobulin treatment in the prevention of childbirth-associated acute exacerbations in multiple sclerosis: a pilot study. J Neurol 243:25–28

    Article  PubMed  CAS  Google Scholar 

  35. Orvieto R, Achiron R, Rotstein Z, Noy S, Bar-Hava I, Achiron A (1999) Pregnancy and multiple sclerosis: a 2-year experience. Eur J Obstet Gynecol Reprod Biol 82:191–194

    Article  PubMed  CAS  Google Scholar 

  36. Sorensen PS, Fazekas F, Lee M (2002) Intravenous immunoglobulin G for the treatment of relapsing-remitting multiple sclerosis: a meta-analysis. Eur J Neurol 9:557–563

    Article  PubMed  CAS  Google Scholar 

  37. Poser CM, Paty DW, Scheinberg L, McDonald WI, Davis FA, Eber GC, Johnson KP, Sibley WA, Silberberg DH, Tourtellotte WW (1983) New diagnostic criteria for multiple sclerosis: guidelines for research protocols. Ann Neurol 13:227–231

    Article  PubMed  CAS  Google Scholar 

  38. Fazekas F, Barkhof F, Filippi M, Grossman RI, Li DK, McDonald WI, McFarland HF, Paty DW, Simon JH, Wolinsky JS, Miller DH (1999) The contribution of magnetic resonance imaging to the diagnosis of multiple sclerosis. Neurology 53:448–456

    Article  PubMed  CAS  Google Scholar 

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© 2004 Springer-Verlag Italia

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Achiron, A. et al. (2004). Early Treatment in Multiple Sclerosis with Intravenous Immunoglobulin: Rationale and Study Design. In: Hommes, O.R., Comi, G. (eds) Early Indicators Early Treatments Neuroprotection in Multiple Sclerosis. Topics in Neuroscience. Springer, Milano. https://doi.org/10.1007/978-88-470-2117-4_12

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  • DOI: https://doi.org/10.1007/978-88-470-2117-4_12

  • Publisher Name: Springer, Milano

  • Print ISBN: 978-88-470-2171-6

  • Online ISBN: 978-88-470-2117-4

  • eBook Packages: Springer Book Archive

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