Published: 2016-02-16

Clinical trials in relapsing-remitting multiple sclerosis (a new proposal for dealing with basic problems and restrictions)

Neuroimmunological Unit, Mossakowski Medical Research Centre, Polish Academy of Sciences
Neuroimmunological Unit, Mossakowski Medical Research Centre, Polish Academy of Sciences Laboratory of Neurogenetics, Department of Neurology, Poznan University of Medical Sciences, Poland
multiple sclerosis clinical trial placebo pathophysiology reference drug


The natural course of multiple sclerosis is characterized by a high variability of pattern, relapse rate and different progression indices. They also present a dramatic impact on the interpretation of treatment trials. Older reports, based on uncontrolled observations are therefore of little value. Currently it is generally accepted that a proper treatment trial should be double blinded and, although probably controversial, that it should be compared with a group of MS patients treated with placebo. Such an approach would be easily acceptable to prove the effectiveness of recently discovered disease modifying drugs. We know that current standard methods of therapy with interferon beta or glatiramer acetate are able to decrease the relapse rate at least by one third, to elongate the intervals between the relapses and to decrease the progression indices. Currently MS is considered a generalized degenerative disease. The lesions are persistent, therefore immunomodulatory treatment has to be started as early as possible. An alternative approach, somewhat suggestive for the use of placebo trials, seems to be a comparison of proposed new drug therapy group with a group of patients treated with a generally accepted reference drug, such as interferon beta or glatiramer acetate, including all clinical and MRI measures.


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  1. Sibley WA and the Therapeutic Claims Committee of the International Federation of Multiple Sclerosis Societies. Therapeutic claims in multiple sclerosis. New York, NY Demos 1988.
  2. Kurtzke J. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 1983;33:1444–1452.
  3. Cutter GR, Baier ML, Rudick RA, Cookfair DL, Fischer JS, Petkau J. et al. Development of a multiple sclerosis functional composite as a clinical trial outcome measure. Brain 1999;122:871–882.
  4. Katz D, Taubenberger JK, Canella B, McFarlin DE, Raine CS, McFarland HF. Correlation between magnetic resonance imaging findings and lesion development in chronic, active multiple sclerosis. Ann Neurol 1993;34:661–669.
  5. Guttmann CR, Ahn SS, Hsu L, Kikinis R, Jolesz FA. The evolution of multiple sclerosis lesions on serial MR. AJNR Am J Neuroradiol 1995;16:1481–1491.
  6. Rudick R, Fischer E, Lee J et al and the Multiple Sclerosis Collaborative Research Group. Use of the brain parenchymal fraction to measure whole brain atrophy in relapsing-remitting MS. Neurology 1999;52:1698–1704.
  7. Johnson KP, Brooks BR, Cohen JA et al. Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: results of a phase III multicenter, double-blind, placebo-controlled trial. Neurology 1995;45:1268–1276.
  8. PRISMS Study Group. Randomized double-blind, placebo-controlled study of interferon ß-1a in relapsing/remitting multiple sclerosis. Lancet 1998;352:1498–1504.
  9. Lublin FD, Reingold SC, and the National Multiple Sclerosis Society (USA) Task Force on Placebo-Controlled Clinical Trials in MS. Placebo-controlled clinical trials in multiple sclerosis: ethical consideration. Ann Neurol 2001;49:677–681.
  10. Polman CH, Reingold SC, Barkhof F, Calabresi PA, Clanet M, Cohen JA et al. Ethics of placebo-controlled clinical trials in multiple sclerosis: a reassessment. Neurology 2009;70:1134–1140.
  11. Su KG, Banker G, Bourdette D, Forte M. Axonal degeneration in multiple sclerosis: the mitochondrial hypothesis. Curr Neurol Neurosci Rep 2009;9:411–417.
  12. Coyle PK. Early treatment of multiple sclerosis to prevent neurologic damage. Neurology 2008;71:S3-S7.
  13. Trapp BD, Peterson J, Ranshoff RM, Rudick R, Mőrk S, Bő L. Axonal transection in the lesions of multiple sclerosis. N Engl J Med 1998;5:278–285.
  14. Mainero C, Benner T, Radding A, van der Kouwe A, Jensen R, Rosen BR, Kinkel RP. In vivo imaging of cortical pathology in multiple sclerosis using ultra-high field MRI. Neurology 2009;12:941–948.
  15. Rudick RA, Trapp BD. Gray-matter injury in multiple sclerosis. N Engl J Med 2009;361:1505–1506.
  16. Fischer E, Lee JC, Nakamura K, Rudick RA. Gray matter atrophy in multiple sclerosis: a longitudinal study. Ann Neurol 2008;64:255–265.
  17. Chard DT, Miller DH. What you see depends how you look: gray matter lesions in multiple sclerosis. Neurology 2009;73:918–919.

How to Cite

Wender M, Michalowska-Wender G. Clinical trials in relapsing-remitting multiple sclerosis (a new proposal for dealing with basic problems and restrictions). JMS [Internet]. 2016Feb.16 [cited 2020Aug.5];84(2):104-6. Available from: