Hostname: page-component-745bb68f8f-v2bm5 Total loading time: 0 Render date: 2025-01-26T21:29:31.922Z Has data issue: false hasContentIssue false
  • English
  • Français

Treatment Optimization in Multiple Sclerosis*

Published online by Cambridge University Press:  16 February 2016

Mark S. Freedman ,
David G. Patry ,
François Grand'Maison ,
Mary Lou Myles ,
Donald W. Paty  and
Daniel H. Selchen
Mark S. Freedman*
Affiliation:
MS Research Clinic, University of Ottawa, Ottawa Hospital General Campus, Ottawa, Ontario, Canada
David G. Patry
Affiliation:
MS Clinic, Department of Clinical Neurosciences, University of Calgary, Foothills Medical Centre, Calgary, Alberta, Canada
François Grand'Maison
Affiliation:
Division of Neurology, University of Sherbrooke, Hôpital Charles LeMoyne, Longueuil, Quebec, Canada
Mary Lou Myles
Affiliation:
University of Alberta, Edmonton, Alberta, Canada
Donald W. Paty
Affiliation:
Division of Neurology, Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
Daniel H. Selchen
Affiliation:
University of Toronto, Trillium Health Centre-Mississauga, St. Michael's Hospital, Toronto, Ontario, Canada
*
Professor of Medicine (Neurology), University of Ottawa, Director, Multiple Sclerosis Research Clinic, The Ottawa Hospital-General Campus, 501 Smyth Road, Ottawa, Ontario K1H 8L6, 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.

The treatment of multiple sclerosis has finally become possible with the advent of the current disease-modifying therapies (DMTs) that have had a significant impact on those living with this disease. Though demonstrating clear efficacy on a number of short-term outcome measures, unfortunately, these agents are not “cures” and many patients with multiple sclerosis continue to experience disease activity in spite of treatment. Clinicians are becoming more comfortable initiating therapy with DMTs, but it is now important to focus attention on monitoring the results of the chosen therapy and deciding whether or not a patient is responding well to treatment. At present, however, clinicians lack criteria for defining optimal versus suboptimal responses to DMTs as well as evidence-based guidelines on how to improve treatment outcomes. Using a recently published model as a framework, The Canadian Multiple Sclerosis Working Group developed practical recommendations on how neurologists can assess the status of patients on DMTs and decide when it may be necessary to modify treatment in order to optimize outcomes. The Canadian Multiple Sclerosis Working Group's recommendations are based on monitoring relapses, neurological progression and MRI activity. Other possible causes of suboptimal treatment responses or treatment failure are also considered.

Type
Review Article
Information
Canadian Journal of Neurological Sciences , Volume 31 , Issue 2 , May 2004 , pp. 157 - 168
Copyright
Copyright © The Canadian Journal of Neurological 2004

Footnotes

*

Recommendations from The Canadian Multiple Sclerosis Working Group

References

1.Goodin, DS, Frohman, EM, Garmany, GP Jr, et al. Disease modifying therapies in multiple sclerosis: report of the Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. Neurology 2002; 58: 169–178.Google Scholar
2.O’Connor, P (Ed.) on behalf of The Canadian Multiple Sclerosis Working Group. Key issues in the diagnosis and management of multiple sclerosis: an overview. Neurology 2002; 59 (Suppl 3): S1-S33.CrossRefGoogle Scholar
3.Oger, J, Freedman, M. Consensus statement of the Canadian MS Clinics Network on the use of disease modifying agents in multiple sclerosis. Can J Neurol Sci 1999; 26: 274.CrossRefGoogle ScholarPubMed
4.Freedman, MS, Blumhardt, LD, Brochet, B, et al. and the Paris Workshop Group. International consensus statement on the use of disease-modifying agents in multiple sclerosis. Mult Scler 2002; 8: 19–23.CrossRefGoogle ScholarPubMed
5.Bashir, K, Buchwald, L, Coyle, PK, et al. MS patient management: optimizing the benefits of immunomodulatory therapy. Int J MS Care 2002; (Suppl): 1–7.Google Scholar
6.McDonald, WI, Compston, A, Edan, G, et al. Recommended diagnostic criteria for multiple sclerosis: guidelines from the International Panel on the diagnosis of multiple sclerosis. Ann Neurol 2001; 50: 121–127.CrossRefGoogle ScholarPubMed
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.CrossRefGoogle ScholarPubMed
8.The IFNB Multiple Sclerosis Study Group and the University of British Columbia MS/MRI Analysis Group. Interferon beta 1b in the treatment of multiple sclerosis: final outcome of the randomized controlled trial. Neurology 1995; 45: 1277–1285.CrossRefGoogle Scholar
9.The IFNß 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: 655–661.CrossRefGoogle Scholar
10.The PRISMS Study Group. Randomized double-blind placebo-controlled study of interferon β-1a in relapsing-remitting multiple sclerosis. Lancet 1998; 352: 1498–1504.CrossRefGoogle Scholar
11.The PRISMS Study Group and the University of British Columbia MS/MRI Analysis Group. PRISMS-4: long-term efficacy of interferon-beta-1a in relapsing MS. Neurology 2001; 56: 1628–1636.CrossRefGoogle Scholar
12.Jacobs, LD, Cookfair, DL, Rudick, RA, et al. Intramuscular interferon beta-1a for disease progression in relapsing remitting multiple sclerosis. The Multiple Sclerosis Collaborative Research Group. Ann Neurol 1996; 39: 285–294.CrossRefGoogle Scholar
13.Weinshenker, BG, Ebers, GC. The natural history of multiple sclerosis. Can J Neurol Sci 1987; 14: 255–261.CrossRefGoogle ScholarPubMed
14.Confavreux, C, Vukusic, S, Moreau, T, Adeleine, P. Relapses and progression of disability in multiple sclerosis. N Engl J Med 2000; 343: 1430–1438.CrossRefGoogle ScholarPubMed
15.Lublin, FD, Cutter, GR, Baier, M. Exacerbation recovery and the progression of multiple sclerosis. Neurology 2000; 54 (Suppl 3): A216 [abstract].Google Scholar
16.Thygesen, P. Evaluation of drug treatment of disseminated sclerosis. Ugeskr Laeger 1965; 127: 1448–1450.Google ScholarPubMed
17.Runmarker, B, Andersen, O. Prognostic factors in a multiple sclerosis incidence cohort with twenty-five years of follow-up. Brain 1993; 116: 117–134.CrossRefGoogle Scholar
18.Bergamaschi, R, Berzuini, C, Romani, A, Cosi, V. Predicting secondary progression in relapsing-remitting multiple sclerosis: a Bayesian analysis. J Neurol Sci 2001; 189: 13–21.CrossRefGoogle ScholarPubMed
19.Confavreux, C, Vukusic, S, Adeleine, P. Early clinical predictors and progression of irreversible disability in multiple sclerosis: an amnesic process. Brain 2003; 126 (Pt 4): 770–782.CrossRefGoogle ScholarPubMed
20.McAlpine, D, Compston, N. Some aspects of the natural history of disseminated sclerosis. Q J Med 1952; 82: 135–167.Google Scholar
21.Kurtzke, JF. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS). Neurology 1983; 33: 1444–1452.CrossRefGoogle ScholarPubMed
22.Fischer, JS, Rudick, RA, Cutter, GR, Reingold, SC, for the National MS Society Clinical Outcomes Assessment Task Force. The Multiple Sclerosis Functional Composite measure (MSFC): an integrated approach to MS clinical outcomes assessment. Mult Scler 1999; 5: 244–250.CrossRefGoogle Scholar
23.Noseworthy, JH, Vandervoort, MK, Wong, CJ, Ebers, GC. Interrater variability with the Expanded Disability Status Scale (EDSS) and Functional Systems (FS) in a multiple sclerosis clinical trial. The Canadian Cooperation MS Study Group. Neurology 1990; 40: 971–975.CrossRefGoogle Scholar
24.Albrecht, H, Wotzel, C, Erasmus, LP, et al. Day-to-day variability of maximum walking distance in MS patients can mislead to relevant changes in the Expanded Disability Status Scale (EDSS): average walking speed is a more constant parameter. Mult Scler 2001; 7: 105–109.CrossRefGoogle ScholarPubMed
25.Bowen, J, Gibbons, L, Gianas, A, Kraft, GH. Self-administered Expanded Disability Status Scale with functional system scores correlates well with a physician-administered test. Mult Scler 2001; 7: 201–206.CrossRefGoogle ScholarPubMed
26.Ve rdier-Taillefer, M-H, Roullet, E, Cesaro, P, Alperovitch, A. Validation of self-reported neurological disability in multiple sclerosis. Int J Epidemiol 1994; 23: 148–154.CrossRefGoogle Scholar
27.Cheng, EM, Hays, RD, Myers, LW, Ellison, GW, Vickrey, BG. How well do self-reported and physician-assessed Expanded Disability Status Scale Scores agree? Neurology 1999; 52 (Suppl 2): A131.Google Scholar
28.Solari, A, Amato, MP, Bergamaschi, R, et al. Accuracy of self-assessment of the minimal record of disability in patients with multiple sclerosis. Acta Neurol Scand 1993; 87: 43–46.CrossRefGoogle ScholarPubMed
29.Ratzker, PK, Feldman, JM, Scheinberg, LC, et al. Self-assessment of neurologic impairment in multiple sclerosis. J Neuro Rehab 1997; 11: 207–211.Google Scholar
30.Schwartz, CE, Vollmer, T, Lee, H and The North American Research Consortium on Multiple Sclerosis Outcomes Study Group. Reliability and validity of two self-report measures of impairment and disability for MS. Neurology 1999; 52: 63–70.CrossRefGoogle ScholarPubMed
31.Hobart, JC, Riazi, A, Lamping, DL, Fitzpatrick, R, Thompson, AJ. Measuring the impact of MS on walking ability: the 12-Item MS Walking Scale (MSWS-12). Neurology 2003; 60: 31–36.CrossRefGoogle ScholarPubMed
32.Schwid, SR, Goodman, AD, Mattson, DH, et al. The measurement of ambulatory impairment in multiple sclerosis. Neurology 1997; 49: 1419–1424.CrossRefGoogle ScholarPubMed
33.Kaufman, M, Moyer, D, Norton, J. The significant change for the Timed 25-foot Walk in the multiple sclerosis functional composite. Mult Scler 2000; 6: 286–290.CrossRefGoogle ScholarPubMed
34.Schwid, SR, Goodman, AD, McDermott, MP, Bever, CF, Cook, SD. Quantitative functional measures in MS: what is a reliable change? Neurology 2002; 58: 1294–1296.CrossRefGoogle ScholarPubMed
35.Joffe, RT, Lippert, GP, Gray, TA, Sawa, G, Horvath, Z. Mood disorder and multiple sclerosis. Arch Neurol 1987; 44: 376–378.CrossRefGoogle ScholarPubMed
36.Minden, SL, Orav, J, Reich, P. Depression in multiple sclerosis. Gen Hosp Psychiatry 1987; 9: 426–434.CrossRefGoogle ScholarPubMed
37.Sadovnick, AD, Remick, RA, Allen, J, et al. Depression and multiple sclerosis. Neurology 1996; 46: 628–632.CrossRefGoogle ScholarPubMed
38.Borras, C, Rio, J, Porcel, J, et al. Emotional state of patients with relapsing-remitting MS treated with interferon beta-1b. Neurology 1999; 52: 1636–1639.CrossRefGoogle ScholarPubMed
39.Patten, SB, Metz, LM. Interferon β-1a and depression in relapsing-remitting multiple sclerosis: an analysis of depression data from the PRISMS clinical trial. Mult Scler 2001; 7: 243–248.Google ScholarPubMed
40.Feinstein, A. An examination of suicidal intent in patients with multiple sclerosis. Neurology 2002; 59: 674–678.CrossRefGoogle ScholarPubMed
41.Beck, AT, Steer, RA. Beck Depression Inventory. San Antonio (TX): Psychological Corporation, 2000.Google Scholar
42.Marder, SR. Psychiatric rating scales. In: Kaplan, IH, Sadock, EJ (Eds), Comprehensive Textbook of Psychiatry. 6th ed. Baltimore, MD: Williams & Wilkins, 1995.Google Scholar
43.Ensel, WM. Measuring depression: the CES-D Scale. In: Lin, N, Dean, A, Ensel, WM, (Eds). Social Support, Life Events, and Depression. New York: Academic Press, 1986.Google Scholar
44.US Preventive Services Task Force. Screening for depression: recommendations and rationale. 2002 May [cited March 17, 2003]. Rockville (MD): Agency for Healthcare Research and Quality. Available from: URL: http://www.ahcpr.gov/clinic/3rduspstf/depression/depressrr.htm.Google Scholar
45.Whooley, MA, Avins, AL, Miranda, J, Browner, WS. Case-finding instruments for depression. Two questions are as good as many. J Gen Intern Med 1997; 12: 439–445.CrossRefGoogle ScholarPubMed
46.Caine, ED, Schwid, SR. Multiple sclerosis, depression, and the risk of suicide. Neurology 2002; 59: 662–663.CrossRefGoogle ScholarPubMed
47.Rio, J, Nos, C, Tintore, M, et al. Assessment of different treatment failure criteria in a cohort of relapsing-remitting multiple sclerosis patients treated with interferon beta: implications for clinical trials. Ann Neurol 2002; 52: 400–406.CrossRefGoogle Scholar
48.Rice, G, Ebers, G. Interferons in the treatment of multiple sclerosis: do they prevent the progression of the disease? Arch Neurol 1998; 55: 1578–1580.CrossRefGoogle ScholarPubMed
49.Liu, C, Blumhardt, LD. Disability outcome measures in therapeutic trials of relapsing-remitting multiple sclerosis: effects of heterogeneity of disease course in placebo cohorts. J Neurol Neurosurg Psychiatry 2000; 68: 450–457.CrossRefGoogle ScholarPubMed
50.Leist, TP, Gobbini, MI, Frank, JA, McFarland, HF. Enhancing magnetic resonance imaging lesions and cerebral atrophy in patients with relapsing multiple sclerosis. Arch Neurol 2001; 58: 57–60.CrossRefGoogle ScholarPubMed
51.Kalkers, NF, Ameziane, N, Bot, JCJ, et al. Longitudinal brain volume measurement in multiple sclerosis: rate of brain atrophy is independent of the disease subtype. Arch Neurol 2002; 59: 1572–1576.CrossRefGoogle ScholarPubMed
52.Trapp, BD, Ransohoff, RM, Fisher, E, Rudick, RA. Neurodegeneration in multiple sclerosis: relationship to neurological disability. Neuroscientist 1999; 5: 48–57.CrossRefGoogle Scholar
53.De Stefano, N, Narayanan, S, Francis, GS, et al. Evidence of axonal damage in the early stages of multiple sclerosis and its relevance to disability. Arch Neurol 2001; 58: 65–70.CrossRefGoogle ScholarPubMed
54.O’Riordan, JI, Thompson, AJ, Kingsley, DPE, et al. The prognostic value of brain MRI in clinically isolated syndromes of the CNS: a 10-year follow-up. Brain 1998; 121: 495–503.CrossRefGoogle Scholar
55.Brex, PA, Ciccarelli, O, O’Riordan, JI, et al. A longitudinal study of abnormalities on MRI and disability from multiple sclerosis. N Engl J Med 2002; 346: 158–164.CrossRefGoogle ScholarPubMed
56.McFarland, HF, Barkhof, F, Antel, J, Miller, DH. The role of MRI as a surrogate outcome measure in multiple sclerosis. Mult Scler 2002; 8: 40–51.CrossRefGoogle ScholarPubMed
57.Molyneux, PD, Filippi, M, Barkhof, F, et al. Correlations between monthly enhanced MRI lesion rate and changes in T2 lesion volume in multiple sclerosis. Ann Neurol 1998; 43: 332–339.CrossRefGoogle ScholarPubMed
58.Kappos, L, Moeri, D, Radue, EW, et al. Predictive value of gadolinium-enhanced magnetic resonance imaging for relapse rate and changes in disability or impairment in multiple sclerosis: a meta-analysis. Gadolinium MRI Meta-analysis Group. Lancet 1999; 353: 964–969.CrossRefGoogle ScholarPubMed
59.Traboulsee, T, for the CMSC Work Group. ENS 2002 Guidelines for a Standardized MRI Protocol for MS. Available at: http://www.mscare.org/ppt/ens2002.pptGoogle Scholar
60.Lucchinetti, C, Bruck, W, Parisi, J, et al. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination. Ann Neurol 2000; 47: 707–717.3.0.CO;2-Q>CrossRefGoogle ScholarPubMed
61.Sriram, U, Barcellos, LF, Villoslada, P, et al. Pharmacogenomic analysis of interferon receptor polymorphisms in multiple sclerosis. Genes Immun 2003; 4: 147–152.CrossRefGoogle ScholarPubMed
62.Ziemssen, T, Kümpfel, T, Klinkert, WE, Neuhaus, O, Hohlfeld, R. Glatiramer acetate-specific T-helper 1- and 2-type cell lines produce BDNF: implications for multiple sclerosis therapy. Brain 2002; 125 (Pt 11): 2381–2391.CrossRefGoogle ScholarPubMed
63.Frohman, E, Phillips, T, Kokel, K, et al. Disease-modifying therapy in multiple sclerosis: strategies for optimizing management. Neurologist 2002; 8: 227–236.CrossRefGoogle ScholarPubMed
64.Rice, GP, Paszner, B, Oger, J, et al. The evolution of neutralizing antibodies in multiple sclerosis patients treated with interferon beta-1b. Neurology 1999; 52: 1277–1279.CrossRefGoogle ScholarPubMed
65.Bertolotto, A, Malucchi, S, Sala, A, et al. Differential effects of three interferon betas on neutralizing antibodies in patients with multiple sclerosis: a follow up study in an independent laboratory. J Neurol Neurosurg Psychiatry 2002; 73: 148–153.CrossRefGoogle Scholar
66.The IFNβ Multiple Sclerosis Study Group and the University of British Columbia MS/MRI Analysis Group. Neutralizing antibodies during treatment of multiple sclerosis with interferon beta-1b: experience during the first three years. Neurology 1996; 47: 889–994.CrossRefGoogle Scholar
67.Antonelli, G, Bagnato, F, Pozzilli, C, et al. Development of neutralizing antibodies in patients with relapsing-remitting multiple sclerosis treated with IFN-beta 1a. J Interferon Cytokine Res 1998; 18: 345–350.CrossRefGoogle Scholar
68.Polman, C, Kappos, L, White, R, et al. Neutralizing antibodies during treatment of secondary progressive MS with interferon β-1b. Neurology 2003; 60: 37–43.CrossRefGoogle ScholarPubMed
69.Sorensen, PS, Koch-Henriksen, N, Ross, C, et al. Neutralizing antibodies against interferon (IFN) beta reduce the clinical effect in relapsing-remitting multiple sclerosis [abstract no. 24]. Presented at the Second Joint Meeting of the Americas and European Committees for Treatment and Research in Multiple Sclerosis (ACTRIMS and ECTRIMS); 2002 Sept 19; Baltimore, Maryland.Google Scholar
70.Brenner, T, Arnon, R, Sela, M, et al. Humoral and cellular immune responses to Copolymer 1 in multiple sclerosis patients treated with Copaxone. J Neuroimmunol 2001; 115: 152–160.Google ScholarPubMed
71.Salama, HH, Hong, J, Zang, YC, et al. Blocking effects of serum reactive antibodies induced by glatiramer acetate treatment in multiple sclerosis. Brain 2003;Aug 22 [Epub ahead of print; DOI: 10.1093/brain/awg269].CrossRefGoogle ScholarPubMed