Hostname: page-component-586b7cd67f-t7czq Total loading time: 0 Render date: 2024-11-28T20:26:00.377Z Has data issue: false hasContentIssue false
  • English
  • Français

Pilot Study of Minocycline in Relapsing-Remitting Multiple Sclerosis

Published online by Cambridge University Press:  02 December 2014

Yunyan Zhang ,
Luanne M Metz ,
V Wee Yong ,
Robert B Bell ,
Michael Yeung ,
David G Patry  and
J Ross Mitchell
Yunyan Zhang
Affiliation:
Departments of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada
Luanne M Metz
Affiliation:
Departments of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada
V Wee Yong
Affiliation:
Departments of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada Department of Oncology, University of Calgary, Calgary, AB, Canada
Robert B Bell
Affiliation:
Departments of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada
Michael Yeung
Affiliation:
Departments of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada
David G Patry
Affiliation:
Departments of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada
J Ross Mitchell
Affiliation:
Departments of Clinical Neurosciences, University of Calgary, Calgary, AB, Canada Department of Radiology, University of Calgary, Calgary, AB, Canada
Rights & Permissions [Opens in a new window]

Abstract

Core share and HTML view are not available for this content. However, as you have access to this content, a full PDF is available via the ‘Save PDF’ action button.
Background:

Current multiple sclerosis (MS) treatment is only partially effective and not all patients respond well. The goal in this study was to evaluate minocycline for its safety, tolerability, and MRI impact as a potential therapy over 36 months after a three month run-in in ten relapsing-remitting (RR) MS patients.

Methods:

Clinical assessments were at three month intervals until six months, then at six month intervals. Three Tesla MRI was performed monthly during the run-in and first six months of treatment, then at 12, 24, and 36 months.

Results:

Treatment was safe and well tolerated. Annualized relapse rate was 1.2 during the run-in and 0.25 during treatment. The proportion of active scans was lower during the first six months of treatment (5.6%, p<0.001) and during the extension (8.7%, p= 0.002) than during the run-in (47.5%). Consistent with these outcomes, mean T2 lesion volume remained stable over three years and percent brain volume change was reduced during year three (-0.37%) of minocycline treatment.

Conclusions:

This trial is limited by small sample and no control group but suggests that minocycline is safe and potentially beneficial in RRMS. This supports further investigation of its efficacy.

résumé:

<span class='bold'>RÉSUMÉ:</span> <span class='bold'> <span class='italic'>Contexte:</span></span>

Le traitement actuel de la sclerose en plaques n’est que partiellement efficace et certains patients n’y repondent pas bien. Le but de cette etude etait d’evaluer la securite, la tolerance et l’impact sur l’IRM de l’administration de minocycline pendant 36 mois, apres une phase de preinclusion de 3 mois, chez dix patients atteints de la forme cyclique remittente de la sclerose en plaques (SEP).

<span class='bold'> <span class='italic'>Méthodes:</span></span>

On a procede a une evaluation clinique aux 3 mois pendant 6 mois, puis aux 6 mois par la suite. Les patients ont subi 3 IRM Tesla par mois au cours de la phase de preinclusion et des 6 premiers mois de traitement, puis aux 12e, 24e et 36e mois.

<span class='bold'> <span class='italic'>Résultats:</span></span>

Le traitement etait sur et bien tolere. Le taux de rechute annualise a ete de 1,2 pendant la phase de preinclusion et de 0,25 pendant le traitement. La proportion de scans montrant une activite etait plus faible pendant les 6 premiers mois de traitement (5,6%, p < 0,01) et pendant l’extension (8,7%, p = 0,002) que pendant la phase de preinclusion (47,5%). Le volume moyen des lesions en T2 est demeure stable pendant 3 ans et le pourcentage de changement du volume cerebral a diminue pendant la troisieme annee de traitement par la minocycline (– 0,37%).

<span class='bold'> <span class='italic'>Conclusions:</span></span>

Cette etude ne comportait qu’un petit nombre de patients et aucun groupe temoin. Cependant, les resultats indiquent que la minocycline est sure et potentiellement benefique dans la SEP cyclique remittente et merite qu’on etudie davantage son efficacite.

Type
Original Articles
Information
Canadian Journal of Neurological Sciences , Volume 35 , Issue 2 , May 2008 , pp. 185 - 191
Copyright
Copyright © The Canadian Journal of Neurological 2008

References

1. Lublin, FD, Reingold, SC. Defining the clinical course of multiple sclerosis: results of an international survey. National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis. Neurology. 1996; 46: 907–11.CrossRefGoogle ScholarPubMed
2. Busche, KD, Fisk, JD, Murray, TJ, Metz, LM. Short term predictors of unemployment in multiple sclerosis patients. Can J Neurol Sci. 2003; 30:137–42.CrossRefGoogle ScholarPubMed
3. O’Connor, KC, Bar-Or, A, Hafler, DA. The neuroimmunology of multiple sclerosis: possible roles of T and B lymphocytes in immunopathogenesis. J Clin Immunol. 2001; 21:81–92.Google Scholar
4. Martin, R, Sturzebecher, CS, McFarland, HF. Immunotherapy of multiple sclerosis: where are we? where should we go? Nat Immunol. 2001; 2:785–8.CrossRefGoogle ScholarPubMed
5. Yong, VW, Power, C, Forsyth, P, Edwards, DR. Metalloproteinases in biology and pathology of the nervous system. Nat Rev Neurosci. 2001; 2:502–11.Google Scholar
6. Brundula, V, Rewcastle, NB, Metz, LM, Bernard, CC, Yong, VW. Targeting leukocyte MMPs and transmigration: Minocycline as a potential therapy for multiple sclerosis. Brain. 2002; 125: 1297–308.CrossRefGoogle ScholarPubMed
7. Compston, A, Coles, A. Multiple Sclerosis. Lancet. 2002; 359: 1221–31.Google Scholar
8. Johnson, KP, Brooks, BR, Cohen, JA, Ford, CC, Goldstein, J, Lisak, RP, 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; 45:1268–76.Google Scholar
9. The IFNB Multiple Sclerosis Study Group. Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double-blind, placebo-controlled trial. Neurology. 1993; 43:655–61.Google Scholar
10. PRISMS (Prevention of Relapses and Disability by Interferon beta-1a Subcutaneously in Multiple Sclerosis) Study Group. Randomised double-blind placebo-controlled study of interferon beta-la in relapsing/remitting multiple sclerosis. Lancet. 1998; 352:1498–504.CrossRefGoogle Scholar
11. Polman, CH, O’Connor, PW, Havrdova, E, Hutchinson, M, Kappos, L, Miller, DH, et al. AFFIRM Investigators. A randomized, placebo-controlled trial of natalizumab for relapsing multiple sclerosis. N Engl J Med. 2006; 354(9):899–910.Google Scholar
12. Comi, G, Filippi, M, Wolinsky, JS, and the European/Canadian Glatiramer Acetate Study Group. European/Canadian multicenter, double-blind, randomized, placebo-controlled study of the effects of glatiramer acetate on magnetic resonance imaging-measured disease activity and burden in patients with relapsing multiple sclerosis. Ann Neurol. 2001; 49:290–7.CrossRefGoogle ScholarPubMed
13. Paty, DW, Li, DK. Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. II. MRI analysis results of a multicenter, randomized, double-blind, placebo-controlled trial. UBC MS/MRI Study Group and the IFNB Multiple Sclerosis Study Group. Neurology. 1993; 43:662–7.Google Scholar
14. Li, DK, Paty, DW. Magnetic resonance imaging results of the PRISMS trial: a randomized, double-blind, placebo-controlled study of interferon-betala in relapsing-remitting multiple sclerosis. Prevention of relapses and disability by interferon-betala subcutaneously in multiple sclerosis. Ann Neurol. 1999; 46:197–206.Google Scholar
15. Stuve, O, Dooley, NP, Uhm, JH, Antel, JP, Francis, GS, Williams, G, et al. Interferon beta-1b decreases the migration of T lymphocytes in vitro: effects on matrix metalloproteinase-9. Ann Neurol. 1996; 40:853–63.Google Scholar
16. Avolio, C, Filippi, M, Tortorella, C, Rocca, MA, Ruggire, M, Agosta, F, et al. Serum MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios in multiple sclerosis: relationships with different magnetic resonance imaging measures of disease activity during IFN-beta-1a treatment. Mult Scler. 2005; 11:441–6.Google Scholar
17. Yong, VW, Wells, J, Giuliani, F, Casha, S, Power, C, Metz, LM. The promise of minocycline in neurology. Lancet Neurol. 2004; 3:744–51.CrossRefGoogle ScholarPubMed
18. Popovic, N, Schubart, A, Goetz, BD, Zhang, SC, Linington, C, Duncan, ID. Inhibition of autoimmune encephalomyelitis by a tetracycline. Ann Neurol. 2002; 51:215–23.Google Scholar
19. Nessler, S, Dodel, R, Bittner, A, Reuss, S, Du, Y, Hemmer, B, et al. Effect of minocycline in experimental autoimmune encephalomyelitis. Ann Neurol. 2002; 52:689–90.CrossRefGoogle ScholarPubMed
20. Giuliani, F, Metz, LM, Wilson, T, Fan, Y, Bar-Or, A, Yong, VW. Additive effect of the combination of glatiramer acetate and minocycline in a model of MS. J Neuroimmunol. 2005; 158: 213–21.Google Scholar
21. Giuliani, F, Fu, S, Metz, LM, Yong, VW. Effective combination of minocycline and interferon-β in a model of multiple sclerosis. J Neuroimmunol. 2005; 165:83–91.Google Scholar
22. Metz, LM, Zhang, Y, Yeung, M, Patry, DG, Bell, RB, Stoian, CA, et al. Minocycline reduces gadolinium enhancing magnetic resonance imaging lesions in multiple sclerosis. Ann Neurol. 2004; 55:756.Google Scholar
23. Mitchell, JR, Karlik, SJ, Lee, DH, Fenster, A. Computer-assisted identification and quantification of multiple sclerosis lesions in MR imaging volumes in the brain. J Magn Reson Imaging. 1994; 4:197–208.Google Scholar
24. Mitchell, JR, Karlik, SJ, Lee, DH, Eliasziw, M, Rice, GP, Fenster, A. The variability of manual and computer assisted quantification of multiple sclerosis lesion volumes. Med Phys. 1996; 23:85–97.Google Scholar
25. Smith, SM, Zhang, Y, Jenkinson, M, Chen, J, Mattews, PM, Federico, A, et al. Accurate, robust and automated longitudinal and cross-sectional brain change analysis. Neuroimage. 2002; 17:479–89.Google Scholar
26. Hardmeier, M, Wagenpfeil, S, Freitag, P, Fisher, E, Rudick, RA, Kooijmans, M, et al. Rate of brain atrophy in relapsing MS decreases during treatment with IFNb-1a. Neurology. 2005; 64:236–40.CrossRefGoogle Scholar
27. Miller, DH, Barkhof, F, Frank, JA, Parker, GJ, Thompson, AJ. Measurement of atrophy in multiple sclerosis: pathological basis, methodological aspects and clinical relevance. Brain. 2002; 125:1676–95.Google Scholar
28. Fisher, E, Rudick, RA, Simon, JH, Cutter, G, Baier, M, Lee, JC, et al. Eight-year follow-up study of brain atrophy in patients with MS. Neurology. 2002; 59:1412–20.Google Scholar
29. Morgen, K, Crawford, AL, Stone, RD, Martin, R, Richert, ND, Frank, JA, et al. Contrast-enhanced MRI lesions during treatment with interferonB-1b predict increase in T1 black hole volume in patients with relapsing-remitting sclerosis. Mult Scler. 2005; 11:146–8.Google Scholar
30. Maier, K, Merkler, D, Gerber, J, Taheri, N, Kuhnert, AV, Williams, SK, et al. Multiple neuroprotective mechanisms of minocycline in autoimmune CNS inflammation. Neurobiol Dis. 2007; 25 (3):514–25. Epub 2007 Jan 18.Google Scholar
31. Zabad, RK, Metz, LM, Todoruk, TR, Zhang, Y, Mitchell, JR, Yeung, M, et al. The clinical response to minocycline in MS is accompanied by beneficial immune changes: a pilot study. Mult Scler. 2007; 38:517–26.Google Scholar
32. Nelissen, I, Martens, E, Van den Steen PE, , Proost, P, Ronsse, I, Opdenakker, G. Gelatinase B/matrix metalloproteinase-9 cleaves interferon-beta and is a target for immunotherapy. Brain. 2003; 126:1371–81.Google Scholar
33. Metz, LM, Li, D, Traboulsee, A, Myles, ML, Duquette, P, Godin, J, et al. Glatiramer acetate combined with minocycline reduces the number of T1 Gd-Enhancing and new T2 lesions compared to glatiramer actetate alone. (Platform) 59th Annual Meeting of the American Academy of Neurology, Boston, May 2007. Neurology. 2007; 68 Suppl 1: A84–85.Google Scholar
34. Bashir, R, Kirby, D. Tolerability of minocycline and IM IFNB-1a in relapsing-remitting multiple sclerosis. Consortium of Multiple Sclerosis Centers: navigating the world of multiple sclerosis. 2005. Abstract.Google Scholar
35. Sicotte, NL, Voskuhl, RR, Bouvier, S, Klutch, R, Cohen, MS, Mazziotta, JC. Comparison of multiple sclerosis lesions at 1.5 and 3.0 Tesla. Invest Radiol. 2003; 38:423–7.Google Scholar