United States open-label glatiramer acetate extension trial for relapsing multiple sclerosis: MRI and clinical correlates

J. S. Wolinsky, P. A. Narayana, K. P. Johnson, A. A. Pruitt, D. Kolson, F. Gonzalez-Scarano, S. J. Bird, D. Pfohl, R. Grossman, L. Mannon, C. C. Ford, E. Greinel, R. Padilla, R. P. Lisak, O. Khan, A. C. Tselis, J. Kamholtz, J. Garbern, R. Lewis, D. LisakL. Tvardek, C. J. Becker, B. Peters, G. Moore, L. W. Myers, G. W. Ellison, R. Baumhefner, L. Rosner, S. Craig, J. R. Bentson, V. Gausche, M. A. Burns, A. Wallace, S. Sinha, H. Panitch, C. Bever, S. Jalbut, E. Katz, K. Conway, A. Gudusky, D. Lefkowitz, M. Boykins, M. Nessaiver, J. W. Rose, J. B. Burns, C. Kawai, J. Tsuruda, N. Carr, A. D. Goodman, S. R. Schwid, M. Petrie, D. A. Shrier, W. Badger, E. W.C. Kwok, J. B. Guarnaccia, T. Vollmer, M. Shepard, G. Sze, K. Martin, N. Kachuck, L. P. Weiner, K. McCarthy, P. M. Colletti, L. Needham, M. Singh, J. W. Lindsey, S. Brod, S. Bhat, E. Cerreta, G. Hunter, S. Remo, S. Duncil, B. R. Brooks, J. Flemming, J. H. Parnell, C. Halvorson, P. Turski, B. Borowski, L. Pardo, R. Misnick, S. Kadosh, G. Shifroni, I. Pinchasi, Y. Stark, D. Ladkani, M. Viswanathan, I. Vainrub, L. Medina, M. Gorbova

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Abstract

After the placebo-controlled extension of the pivotal US trial of glatiramer acetate for the treatment of relapsing multiple sclerosis ended, 208 participants entered an open-label, long-term treatment protocol. Magnetic resonance imaging (MRI) was added to the planned evaluations of these subjects to determine the consequences of long-term treatment on MRI-defined pathology and evaluate its clinical correlates. Of the 147 subjects that remained on long-term follow-up, adequate images were obtained on 135 for quantitative MRI analysis. The initial imaging sessions were performed between June 1998 and January 1999 at 2447 ± 61 days (mean±standard deviation) after the subject's original randomization. Clinical data from a preplanned clinical visit were matched to MRI within 3 ± 51 days. At imaging, 66 patients originally randomized to placebo (oPBO) in the pivotal trial had received glatiramer acetate for 1476 ± 63 days, and 69 randomized to active treatment with glatiramer acetate (oGA) were on drug for 2433 ± 59 days. The number of documented relapses in the 2 years prior to entering the open-label extension was higher in the group originally randomized to placebo (oPBO=1.86 ± 1.78, oGA=1.03 ± 1.28; P=0.002). The annualized relapse rate observed during the open-label study was similar for both groups (oPBO=0.27, ±0.45 oGA=0.28 ± 0.40), but the reduction in rate from the placebo-controlled phase was greater for those beginning therapy with GA (oPBO reduced by 0.66 ± 0.71, oGA reduced by 0.23 ± 0.58; P=0.0002). One or more gadolinium enhancing lesions were found in 27.4% of all patients (number of distinct enhancements=1.16 ± 2.52, total enhanced tissue volume=97 ± 26 μl). The risk of having an enhancement was higher in those with relapses during the open-label extension (odds ratio 4.65, 95% confidence interval (Cl) 2.0 to 10.7; P=0.001). The odds for finding an enhancement was 2.5 times higher for those patients originally randomized to placebo (Cl 1.1 to 5.4; P=0.02) compared to those always on glatiramer acetate. MRI-metrics indicative of chronic pathology, particularly measures of global cerebral tissue loss (atrophy), were uniformly worse for those originally on placebo. These observations enrich our long-term follow up of the clinical consequences of treatment with glatiramer acetate to include its apparent effects on MRI-defined pathology. They show that the effect of glatiramer acetate on enhancements is definite, but modest, consistent with the drug's described mechanisms of action, and that a delay in initiating treatment results in progression of MRI-measured pathology that can be prevented.

Original languageEnglish (US)
Pages (from-to)33-41
Number of pages9
JournalMultiple Sclerosis
Volume7
Issue number1
DOIs
Publication statusPublished - Jan 1 2001

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Keywords

  • Clinical trial
  • Copaxone
  • Copolymer I
  • Glatiramer acetate
  • Magnetic resonance imaging
  • Multiple sclerosis

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Wolinsky, J. S., Narayana, P. A., Johnson, K. P., Pruitt, A. A., Kolson, D., Gonzalez-Scarano, F., ... Gorbova, M. (2001). United States open-label glatiramer acetate extension trial for relapsing multiple sclerosis: MRI and clinical correlates. Multiple Sclerosis, 7(1), 33-41. https://doi.org/10.1191/135245801667520627