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Multiple Sclerosis
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Intravenous immunoglobulin in primary and secondary chronic progressive multiple sclerosis: a randomized placebo controlled multicentre study

D. Pöhlau

Department of Neurology, Multiple Sclerosis Center, Kamillus-Klinik Asbach, Department of Neurology, Ruhr University Bochum, Germany

H. Przuntek

Department of Neurology, Ruhr University Bochum, Germany

M. Sailer

Clinical Center for Neurophysiology, Otto-von-Guericke University, Magdeburg, Germany

F. Bethke

Department of Neurology, University of Münster, Münster, Germany

J. Koehler

Department of Neurology, University of Mainz, Mainz, Germany

N. König

Department of Neurology, Marianne-Strauss Klinik, Berg, Germany

C. Heesen

Joystone Gbadamosi, University Medical Center, Hamburg, Germany

P. Späth

Department of Research and Development, ZLB Bern, Switzerland

I. Andresen

Department of Research and Development, ZLB Bern, Switzerland, irmgard.andresen{at}csibehring.com

In patients with relapsing-remitting multiple sclerosis (MS), IVIG was shown to reduce the relapse rate and progression of disability. In patients with chronic progressive MS, a beneficial effect of IVIG was not documented in placebo controlled studies. This trial investigated the influence of IVIG in primary (PPMS) and secondary (SPMS) chronic progressive MS. Two-hundred and thirty-one patients stratified for PPMS (n = 34) and SPMS (n = 197) were randomly assigned to IVIG 0.4 g/kg per month or to placebo for 24 months. Primary endpoints were 1) the time to sustained progression of disease identified as worsening of the expanded disability status scale (EDSS) sustained for 3 months, and 2) the improvement of neurological functions defined by a patient's best EDSS score. Secondary endpoints were the proportion of patients with sustained progression, the relapse rate, the assessment of fine motor skills, visual evoked potentials, contrast sensitivity, depression and quality of life. Analysis of the intention-to-treat (ITT) population of combined PPMS and SPMS patients showed that the mean time to sustained progression was 74 weeks in the IVIG compared with 62 weeks in the placebo group (P = 0.0406). When PPMS and SPMS patients were analysed separately, the time to sustained progression was also longer in the IVIG group, but the difference was not significant. There was no IVIG-mediated improvement in neurological functions.

In the combined per protocol (PP) treated patients, IVIG treatment prolonged time to sustained progression by 13 weeks (P = 0.0396). PPMS patients, but not SPMS patients showed a slight favourable IVIG effect on the best EDSS score.

In the combined ITT population there were less patients with sustained progression in the IVIG than in the placebo group (P = 0.028). The difference was significant in PPMS ( P = 0.016), but not in SPMS patients. In the combined PP population, there was a trend for a favorable IVIG effect on the rates of patients with sustained progression. In patients with PPMS, this IVIG effect reached significance (P = 0.036). Other secondary endpoints did not show significant differences between treatment groups. Eighteen patients with PPMS and 102 patients with SPMS withdrew from the study for various reasons. Treatment was generally well tolerated. It was concluded that monthly IVIG infusion could delay progression of disease in patients with PPMS, and that there was a trend in favour of IVIG treatment in patients with SPMS. Multiple Sclerosis 2007; 13: 1107—1117. http://msj.sagepub.com

Key Words: IVIG • primary • secondary progressive multiple sclerosis

References

  • Sorensen PS The role of intravenous immunoglobulin in the treatment of multiple sclerosis. 7th European Charcot Foundation Lecture. J Neurol Sci 2003; 206: 123—30.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Stangel M., Gold R. Intravenous immunoglobulins in MS. The International MS Journal 2005; 12: 4—10.
  • Fazekas F., Deisenhammer F., Strasser-Fuchs S., Nahler G., Mamoli B., for the Austrian Immunoglobulin in Multiple Sclerosis Study Group. Randomized placebo-controlled trial of monthly intravenous immunoglobulin therapy in relapsing-remitting multiple sclerosis. Lancet 1997; 349: 589—93.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Achiron A., Gabbay U., Gilad R., Hassin-Baer S., Barak Y., Gornish M. et al. Intravenous immunoglobulin treatment in multiple sclerosis: effect on relapses. Neurology 1998; 50: 398—402.[Abstract/Free Full Text]
  • Sorensen PS, Wanscher B., Jensen C., Schreiber K., Blinkenber M., Ravnborg M. et al. Intravenous immunoglobulin G reduces MRI activity in relapsing multiple sclerosis. Neurology 1998; 50: 1273—81.[Abstract/Free Full Text]
  • Lewanska M., Siger-Zajdel, Selmaj K. No difference in efficacy of two different doses of intravenous immunoglobulins in MS: clinical and MRI assessment. Eur J Neurol 2002; 9: 565—72.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Noseworthy JH, Lucchinetti C., Rodriguez M., Weinshenker BG Multiple sclerosis. N Engl J Med 2000; 343: 938—52.[Free Full Text]
  • Hommes O., Soerenson PS, Fazekas F., Maas Enriquez M, Koelmel H., Fernandez O. et al. Intravenous immunoglobulin in secondary progressive multiple sclerosis: randomized placebo-controlled trial. Lancet 2004; 364: 1149—56.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • European Study Group on Interferon Beta-1b in Secondary Progressive MS. Placebo-controlled multicentre randomized trial of interferon beta-1b in treatment of secondary progressive multiple sclerosis. Lancet 1998; 352: 1491—97.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Secondary Progressive Efficacy Clinical Trial of Recombinant Interferon-Beta-1a in MS (SPECTRIMS) Study Group. Randomized controlled trial of interferon-beta-1a in secondary progressive MS: clinical results. Neurology 2001; 56: 1496—504.[Abstract/Free Full Text]
  • Goodkin DE, the North American Study Group on Interferon Beta-1b in Secondary Progressive MS. Clinical and MRI results of a 3-year randomized controlled trial. Neurology 2000; 54: 2352 (abstract).
  • Filippini G., Munari L., Incorvaia B., Ebers GC, Polman C., D'Amico R., Rice Gpa. Interferons in relapsing-remitting multiple sclerosis: a systematic review. Lancet 2003; 361: 545—52.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Hartung HP, Gonsette R., Koenig N., Kwiecinski H., Guseo A., Morissey SP et al. Mitoxantrone in progressive multiple sclerosis: a placebo-controlled double-blind, randomized, multicentre trial. Lancet 2002; 360: 2018—25.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Leary SM, Thompson AJ Primary progressive multiple sclerosis. Current and future treatment options. CNS Drugs 2005; 19: 369—76.
  • Noseworthy JH Management of multiple sclerosis: current trials and future options. Curr Opin Neurol 2003; 16: 289—97.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Poehlau D., Federlein J., Postert T., Sailer M., Bethke F., Kappos L. et al. Intravenous immunoglobulin (IVIG) treatment for patients with primary or secondary progressive multiple sclerosis — outline of a double-blind randomized, placebo-controlled trial. Multiple Sclerosis 1997; 3: 149—52.[Abstract/Free Full Text]
  • Kurtzke JF Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 1983; 33: 1444—52.[Abstract/Free Full Text]
  • Kurtzke JF Natural history and clinical outcome measures for multiple sclerosis studies. Why at the present time does EDSS scale remain a preferred outcome measures to evaluate disease evolution? Neurol Sci 2000; 21: 339—41.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Goodkin DE, Hertsgaard D., Seminary J. Upper extremity function in multiple sclerosis: improving assessment sensitivity with box-and-block and nine-hole peg tests. Arch Phys Med Rehabil 1988; 69: 850—54.[Web of Science][Medline] [Order article via Infotrieve]
  • Mathiowetz V., Volland G., Kashman N., Weber K. Adult norms for the box and block test of manual dexterity. Am J Occup Ther 1985; 39: 386—91.[Web of Science][Medline] [Order article via Infotrieve]
  • Lycke J., Tolleson PO, Frisen L. Asymptomatic visual loss in multiple sclerosis. J Neurol 2001; 248: 1079—86.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • van Diemen HA, Lanting P., Koetsier JC, Strijers RL, van Walbeek HK, Polman CH Evaluation of the visual system in multiple sclerosis: a comparative study of diagnostic tests. Clin Neurol Neurosurg 1992; 94: 191—95.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Brigell M., Bach M., Barber C., Kawasaki K., Kooijman A. Guidelines for calibration of stimulus and recording parameters used in clinical electrophysiology of vision. Calibration Standard Committee of the International Society for Clinical Electrophysiology of Vision (ISCEV). Doc Ophthalmol 1998; 95: 1—14.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Celesia GG, Bodis-Wollner I., Chatrian GE, Harding GF, Sokol S., Spekrijse H. Recommended standards for electroretinograms and visual evoked potentials. Report of an IFCN Committee. Electroencephalogr Clin Neurophysiol 1993; 87: 421—36.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Andresen EM, Malmgren JA, Carter WB, Patrick DL Screening for depression in well older adults: evaluation of a short form of the CES-D (Center for Epidemiologic Studies Depression Scale). Am J Prev Med 1994; 10: 77—84.[Web of Science][Medline] [Order article via Infotrieve]
  • Verdier-Taillefer MH, Gourlet V., Fuhrer R., Alperovitch A. Psychometric properties of the Center for Epidemiologic Studies — Depression Scale in multiple sclerosis. Neuroepidemiology 2001; 20: 262—67.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Bullinger M., Kirchberger I. SF-36. Fragebogen zum Gesundheitszustand. Hogrefe, 1998.
  • Nortvedt MW, Riise T., Myhr KM, Nyland HI Quality of life in multiple sclerosis: measuring the disease effect more broadly. Neurology 1999; 53: 1098—103.[Abstract/Free Full Text]
  • Revesz T., Kidd D., Thompson AJ, Barnard RO, McDonald WI A comparison of the pathology of primary and secondary progressive multiple sclerosis. Brain 1994; 117: 759—65.[Abstract/Free Full Text]
  • Van Engelen BGM, Hommes OR, Pinckers A., Cruysberg JR, Barkhof F., Rodriguez M. Improved vision after intravenous immunoglobulin in stable demylinating optic neuritis. Ann Neurol 1992; 32: 834—35.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Noseworthy JH, O'Brien PC, van Engelen BG, Rodriguez M. Intravenous immunoglobulin therapy in multiple sclerosis: progress from remyelination in Theiler's virus model to a randomized, double-blind, placebo-controlled clinical trial. J Neurol Neurosurg Psychiatry 1994; 57(Suppl): 11—14.[Abstract/Free Full Text]
  • Rodriguez M., Miller DJ, Lennon VA Immunoglobulins reactive with myelin basic protein promote CNS remyelination. Neurology 1996; 46: 538—45.[Abstract/Free Full Text]
  • Noseworthy J., Weinshenker B., O'Brien P., Weis JA, Pettersen T., Windebank JA et al. Immunoglobulin administration (IVIg) does not reverse recently acquired, apparently permanent weakness in multiple sclerosis (MS) (abstract). Ann Neurol 1997; 42: A421.
  • Noseworthy J., O'Brien P., Pettersen T., Weinshenker BG, Cross SA, Leavitt JA et al. Immunoglobulin administration (IVIg) does not reverse visual acuity loss in longstanding optic neuritis associated with multiple sclerosis. Ann Neurol 1998; 44: A504.
  • Noseworthy JH, Gold R., Hartung HP Treatment of multiple sclerosis: recent trials and future perspectives. Curr Opin Neurol 1999; 1: 279—93.
  • Stangel M., Boegner F., Klatt CH, Hofmeister C., Seyfert S. Placebo controlled pilot trial to study the remyelinating potential of intravenous immunoglobulins in multiple sclerosis. J Neurol Neurosurg Psychiatry 2000; 68: 89—92.[Abstract/Free Full Text]
  • Fazekas F., Sorensen PS, Filippi M., Ropele S., Lin X., Koelmel HW et al. MRI results from the European study on intravenous immunoglobulin in secondary progressive multiple sclerosis (ESIMS). Multiple Sclerosis 2005; 11: 433—40.[Abstract/Free Full Text]
  • Maor Y., Olmer L., Mozes B. The relation between objective and subjective impairment in cognitive function among multiple sclerosis patients — the role of depression. Multiple Sclerosis 2001; 7: 131—35.[Abstract/Free Full Text]
  • Rice GP, Oger J., Duquette P., Francis GS, Belanger M., Laplante S., Grenier JF Treatment with interferon beta-1b improves quality of life in multiple sclerosis. Can J Neurol Sci 1999; 26: 276—82.[Web of Science][Medline] [Order article via Infotrieve]
  • Jacobs LD, Beck RW, Simon JH, Kinkel RP, Brownscheidle CM, Murray TJ et al. CHAMPS study goup. Intramuscular interferon beta-1a initiated during a first demyelinating event in multiple sclerosis. N Engl J Med 2000; 343: 898—904.[Abstract/Free Full Text]
  • Comi G., Filippi M., Barkhof F., Durelli L., Edan G., Fernandez O. et al. Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomised study. Lancet 2001; 357: 1576—82.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Goodin DS, Frohman EM, Garmany Jr GP, Halper J., Likosky WH, Lublin FD et al. Disease modifying therapies in multiple sclerosis. Report of the therapeutics and technology assessment subcommittee of the American Academy of Neurology and the MS council for clinical practice guidelines. Neurology 2002; 58: 169—78.[Free Full Text]
  • Poehlau D., and the IVIG Study Group. Treatment of chronic progressive multiple sclerosis with intravenous immunoglobulins — interim results on drug safety of an ongoing study. Multiple Sclerosis 2000; 6(Suppl 2): 521—23.
  • Zaidan R., Al Moallem M., Wani BA, Shameena AR, Al Tahan AR, Daif AK, Al Rajeh S. Thrombosis complicating high dose intravenous immunoglobulin: report of three cases and review of the literature. European Journal of Neurology 2003; 10: 367—72.[CrossRef][Web of Science][Medline] [Order article via Infotrieve]
  • Dalakas MC, Clark WM Strokes. Thromboembolic events and IVIg. Rare incidents blemish an excellent safety record. Neurology 2003; 60: 1726—37.[Free Full Text]

This version was published on November 1, 2007

Multiple Sclerosis, Vol. 13, No. 9, 1107-1117 (2007)
DOI: 10.1177/1352458507078400
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