Defining Suboptimal Response to MS Treatment: MRI Outcome
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Defining Suboptimal Response to MS Treatment: MRI Outcome

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  • However, there is more confusion than consensus on how best to use MRI in the routine care of MS patients in clinical practice. An informal survey of Neurologists who deal exclusively with MS reveals a range of opinion on the best use of MRI for managing patient care. On one extreme, are those that feel the role of MRI is best limited to supporting the diagnosis of MS. The other extreme are those that modify treatment based on any signs of new disease activity on MRI. The rest are sure how best to use, but like to routinely follow the evolution of the disease process.
  • However, there is more confusion than consensus on how best to use MRI in the routine care of MS patients in clinical practice. An informal survey of Neurologists who deal exclusively with MS reveals a range of opinion on the best use of MRI for managing patient care. On one extreme, are those that feel the role of MRI is best limited to supporting the diagnosis of MS. The other extreme are those that modify treatment based on any signs of new disease activity on MRI. The rest are sure how best to use, but like to routinely follow the evolution of the disease process.
  • At the end of this presentation, the audience will have an understanding how MRI can be used to detect worsening disease, in terms of a build up of pathological lesions, but this may not necessarily reflect the clinical status of the patient. The audience will also learn of the potential for MRI to have a greater role in guiding treatment decisions as our understanding of MS and of new MRI techniques improves.
  • At the end of this presentation, the audience will have an understanding how MRI can be used to detect worsening disease, in terms of a build up of pathological lesions, but this may not necessarily reflect the clinical status of the patient. The audience will also learn of the potential for MRI to have a greater role in guiding treatment decisions as our understanding of MS and of new MRI techniques improves.
  • At the end of this presentation, the audience will have an understanding how MRI can be used to detect worsening disease, in terms of a build up of pathological lesions, but this may not necessarily reflect the clinical status of the patient. The audience will also learn of the potential for MRI to have a greater role in guiding treatment decisions as our understanding of MS and of new MRI techniques improves.
  • At the end of this presentation, the audience will have an understanding how MRI can be used to detect worsening disease, in terms of a build up of pathological lesions, but this may not necessarily reflect the clinical status of the patient. The audience will also learn of the potential for MRI to have a greater role in guiding treatment decisions as our understanding of MS and of new MRI techniques improves.
  • At the end of this presentation, the audience will have an understanding how MRI can be used to detect worsening disease, in terms of a build up of pathological lesions, but this may not necessarily reflect the clinical status of the patient. The audience will also learn of the potential for MRI to have a greater role in guiding treatment decisions as our understanding of MS and of new MRI techniques improves.
  • At the end of this presentation, the audience will have an understanding how MRI can be used to detect worsening disease, in terms of a build up of pathological lesions, but this may not necessarily reflect the clinical status of the patient. The audience will also learn of the potential for MRI to have a greater role in guiding treatment decisions as our understanding of MS and of new MRI techniques improves.
  • At the end of this presentation, the audience will have an understanding how MRI can be used to detect worsening disease, in terms of a build up of pathological lesions, but this may not necessarily reflect the clinical status of the patient. The audience will also learn of the potential for MRI to have a greater role in guiding treatment decisions as our understanding of MS and of new MRI techniques improves.
  • At the end of this presentation, the audience will have an understanding how MRI can be used to detect worsening disease, in terms of a build up of pathological lesions, but this may not necessarily reflect the clinical status of the patient. The audience will also learn of the potential for MRI to have a greater role in guiding treatment decisions as our understanding of MS and of new MRI techniques improves.
  • At the end of this presentation, the audience will have an understanding how MRI can be used to detect worsening disease, in terms of a build up of pathological lesions, but this may not necessarily reflect the clinical status of the patient. The audience will also learn of the potential for MRI to have a greater role in guiding treatment decisions as our understanding of MS and of new MRI techniques improves.
  • At the end of this presentation, the audience will have an understanding how MRI can be used to detect worsening disease, in terms of a build up of pathological lesions, but this may not necessarily reflect the clinical status of the patient. The audience will also learn of the potential for MRI to have a greater role in guiding treatment decisions as our understanding of MS and of new MRI techniques improves.
  • At the end of this presentation, the audience will have an understanding how MRI can be used to detect worsening disease, in terms of a build up of pathological lesions, but this may not necessarily reflect the clinical status of the patient. The audience will also learn of the potential for MRI to have a greater role in guiding treatment decisions as our understanding of MS and of new MRI techniques improves.
  • At the end of this presentation, the audience will have an understanding how MRI can be used to detect worsening disease, in terms of a build up of pathological lesions, but this may not necessarily reflect the clinical status of the patient. The audience will also learn of the potential for MRI to have a greater role in guiding treatment decisions as our understanding of MS and of new MRI techniques improves.
  • At the end of this presentation, the audience will have an understanding how MRI can be used to detect worsening disease, in terms of a build up of pathological lesions, but this may not necessarily reflect the clinical status of the patient. The audience will also learn of the potential for MRI to have a greater role in guiding treatment decisions as our understanding of MS and of new MRI techniques improves.
  • At the end of this presentation, the audience will have an understanding how MRI can be used to detect worsening disease, in terms of a build up of pathological lesions, but this may not necessarily reflect the clinical status of the patient. The audience will also learn of the potential for MRI to have a greater role in guiding treatment decisions as our understanding of MS and of new MRI techniques improves.
  • At the end of this presentation, the audience will have an understanding how MRI can be used to detect worsening disease, in terms of a build up of pathological lesions, but this may not necessarily reflect the clinical status of the patient. The audience will also learn of the potential for MRI to have a greater role in guiding treatment decisions as our understanding of MS and of new MRI techniques improves.
  • A key point is that when MRI’s are compared, the interpretation is critically dependent on good quality data. A standardized MRI will provide optimal information. The interpretation of the importance of this information for the patient will then be at the discretion of the local physician.
  • At the end of this presentation, the audience will have an understanding how MRI can be used to detect worsening disease, in terms of a build up of pathological lesions, but this may not necessarily reflect the clinical status of the patient. The audience will also learn of the potential for MRI to have a greater role in guiding treatment decisions as our understanding of MS and of new MRI techniques improves.
  • At the end of this presentation, the audience will have an understanding how MRI can be used to detect worsening disease, in terms of a build up of pathological lesions, but this may not necessarily reflect the clinical status of the patient. The audience will also learn of the potential for MRI to have a greater role in guiding treatment decisions as our understanding of MS and of new MRI techniques improves.
  • The future of MRI in clinical trials is a combination of outcome measures for the inflammatory and degenerative aspects of the disease. The value of MRI in clinical practice will improve once we are able to better understand the prognostic value of early MRI changes, and the significance of new MRI activity in the “clinically stable” patient.

Defining Suboptimal Response to MS Treatment: MRI Outcome Defining Suboptimal Response to MS Treatment: MRI Outcome Presentation Transcript

  • Tony Traboulsee, MD (Neurology) University of British Columbia CMSC June 5th, 2004 Toronto, Ontario Defining suboptimal response to MS treatment: MRI outcome
  • Disclosure
    • I have received honoraria from the Consortium of MS Centers and from all the major pharmaceutical companies currently involved in MS clinical trials of DMTs.
    • 1984
    • MRI detects clinically silent lesions.
    • Its role in monitoring individual patients is unknown.
    0.15 Tesla MRI, UBC
  • What is the value of MRI in monitoring MS patients?
    • 1. Does MRI predict if a patient will have clinical relapses?
    • Does MRI predict clinical disability?
    • Does MRI predict treatment response?
    • Is the clinical MRI data reliable?
    Dr. T. Traboulsee, UBC MS/MRI Research Group
  • What is the value of MRI in monitoring MS patients?
    • 1. Does MRI predict if a patient will have clinical relapses?
    • Does MRI predict clinical disability?
    • Does MRI predict treatment response?
    • Is the clinical MRI data reliable?
    Dr. T. Traboulsee, UBC MS/MRI Research Group
  • Bashir analog model for assessing the effectiveness of therapeutic strategies Reproduced without permission from International Journal of MS Care 2002 (suppl):1-7
  • Freedman analog model for assessing the effectiveness of MS therapies. Reproduced without permission from Canadian Journal of Neurological Sciences 2004; 31(2)
  • Why do any test in medicine?
    • To monitor the disease course.
    • To predict clinical outcome.
    • To modify therapy.
    Dr. T. Traboulsee, UBC MS/MRI Research Group
  • Freedman analog model for assessing the effectiveness of MS therapies. Reproduced without permission from Canadian Journal of Neurological Sciences 2004; 31(2)
  • Reproduced without permission from Canadian Journal of Neurological Sciences 2004; 31(2)
  • What is the value of MRI in monitoring MS patients? Dr. T. Traboulsee, UBC MS/MRI Research Group
  • Does a single MRI Predict Relapses?
    • MRI abnormalities in CIS predict CDMS (Brex 14 year natural history cohort NEJM 2003)
    • Gad activity predicts higher rate of conversion from CIS to CDMS (CHAMPS)
    Dr. T. Traboulsee, UBC MS/MRI Research Group
  • Does a single MRI Predict Relapses?
    • An initial MRI with no gad lesions would predict 1.3 relapses in the next year.
    • An initial MRI with 10 gad lesions would predict 1.6 relapses in the next year.
    • Kappos Meta Analysis of 307 patients, Lancet 1999
    Dr. T. Traboulsee, UBC MS/MRI Research Group
  • Do Serial MRI Predict Relapses?
    • PPV 0.2 when using monthly gad activity on MRI predicting relapse at 6 months (Koziol AJNR 2002)
    • R = 0.25 for monthly MRI gad activity correlating with relapses (Rovaris AJNR 2003)
    • The relative risk of having a relapse at 1 or 2 years was slightly increased ( RR 1.13) by the presence of gad lesions with 6 monthly scans (Kappos Lancet 1999)
    Dr. T. Traboulsee, UBC MS/MRI Research Group
  • What is the value of MRI in monitoring MS patients?
    • 1. Does MRI predict if a patient will have clinical relapses?
    • Does MRI predict clinical disability?
    • Does MRI predict treatment response?
    • Is the clinical MRI data reliable?
    Dr. T. Traboulsee, UBC MS/MRI Research Group
  • Does a single MRI Predict Disability?
    • CIS patients with larger number and volume of T2 lesions tend to have greater disability at 14 years (Brex NEJM 2002)
    • There was no relationship between gad enhancing lesions at baseline and EDSS at 2 years. ( Kappos Meta Analysis, Lancet 1999)
    Dr. T. Traboulsee, UBC MS/MRI Research Group
  • Do serial MRI Predict Disability?
    • New T2 activity weakly correlated with relapses (r=0.2) but not with disability at 5 years .
    • Change in BOD weakly correlated with relapses (r=0.2) and with EDSS (r=0.3)
    Paty, IFNB RRMS study, 115 Placebo patients followed with annual MRI for 5 years
  • Do serial MRI Predict Disability?
    • New T2 activity weakly predicts disability at 2-3 years of follow-up (r=0.13, p=0.02).
    Filippi et al, pooled data of 281 MS patients, Neurology 1995
  • Do serial MRI Predict Disability?
    • The most active patients on MRI have a worse prognosis than the less active ones.
    • However, there is so much overlap between groups that one cannot yet predict prognosis for individual patients .
    • Paty, AAN 1992
  • What is the value of MRI in monitoring MS patients?
    • 1. Does MRI predict if a patient will have clinical relapses?
    • Does MRI predict clinical disability?
    • Does MRI predict treatment response?
    • Is the clinical MRI data reliable?
    Dr. T. Traboulsee, UBC MS/MRI Research Group
  • Does MRI predict Treatment Success? Observations from RRMS:
    • Studies have shown up to a 90% suppression of new gadolinium enhancement lesions.
    • These studies also showed no net accumulation of total T2 lesion load.
    • However, the clinical impact on relapses is only modest (33% reduction), and the long term impact on clinical disability remains controversial.
  • Change from Baseline in MRI Area Pivotal IFN beta 1b RRMS study T2 BOD is suppressed compared to placebo
  • IFN Beta-1a: % Change of BOD from Baseline Population Distribution 0 10 20 30 -40 -20 0 20 40 60 80 100 120 140 160 180 200 % of patients % change in BOD from baseline Placebo Rebif 44 TIW GOOD MRI Outcome POOR MRI Outcome
  • Does MRI predict Treatment Success? Observations from SPMS:
    • Studies have shown similar suppression of new inflammatory MRI activity and on T2 BOD as seen in RRMS.
    • However, there is no consistent clinical impact on disability.
  • What is the value of MRI in monitoring MS patients?
    • 1. Does MRI predict if a patient will have clinical relapses?
    • Does MRI predict clinical disability?
    • Does MRI predict treatment response?
    • Is the clinical MRI data reliable?
    Dr. T. Traboulsee, UBC MS/MRI Research Group
  • CMSC MRI Protocol
    • If a follow-up MRI is to be done, it should be performed by the standardized MRI protocol.
    Dr. A. Traboulsee and the CMSC work group
  • Total Lesion Frequency and EDSS 12 24 36 48 Months Number of Gd enhancing lesions 10 8 6 4 2 5 4 3 2 EDSS Kindly provided by Joe Frank, NIH
  • Why do any test in medicine?
    • To monitor the disease course.
    • To predict clinical outcome.
    • To modify therapy.
    Dr. T. Traboulsee, UBC MS/MRI Research Group
  • How can this be applied to individual patients?
    • There is so much overlap between groups that one cannot yet predict prognosis for individual patients.
    • Paty, AAN 1992
    Dr. T. Traboulsee, UBC MS/MRI Research Group
  • Conclusion
    • Treat the patient,
    • not the test.
    Dr. T. Traboulsee, UBC MS/MRI Research Group.