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Enhancing MS Treatment through MRI Monitoring

Explore the value of MRI in monitoring MS patients for predicting relapses, disability, treatment response, and reliability of clinical data by Dr. T. Traboulsee at UBC. Understand the predictive power of single and serial MRIs for MS outcomes. Illustrations from analog models by Bashir and Freedman. Learn how MRI findings impact clinical management decisions and treatment success in MS patients.

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Enhancing MS Treatment through MRI Monitoring

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  1. Tony Traboulsee, MD (Neurology) University of British ColumbiaCMSC June 5th, 2004Toronto, Ontario Defining suboptimal response to MS treatment: MRI outcome

  2. 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.

  3. 1984 MRI detects clinically silent lesions. Its role in monitoring individual patients is unknown. 0.15 Tesla MRI, UBC

  4. 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

  5. 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

  6. Bashir analog model for assessing the effectiveness of therapeutic strategies Reproduced without permission from International Journal of MS Care 2002 (suppl):1-7

  7. Freedman analog model for assessing the effectiveness of MS therapies. Reproduced without permission from Canadian Journal of Neurological Sciences 2004; 31(2)

  8. 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

  9. Freedman analog model for assessing the effectiveness of MS therapies. Reproduced without permission from Canadian Journal of Neurological Sciences 2004; 31(2)

  10. Reproduced without permission from Canadian Journal of Neurological Sciences 2004; 31(2)

  11. What is the value of MRI in monitoring MS patients? Dr. T. Traboulsee, UBC MS/MRI Research Group

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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

  19. 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

  20. 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

  21. 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.

  22. Pivotal IFN beta 1b RRMS study T2 BOD is suppressed compared to placebo Change from Baseline in MRI Area

  23. Rebif 44 TIW Placebo GOOD MRI Outcome POOR MRI Outcome IFN Beta-1a: % Change of BOD from Baseline Population Distribution 30 20 % of patients 10 0 200 -40 180 120 -20 0 20 40 60 80 100 140 160 % change in BOD from baseline

  24. 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.

  25. 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

  26. 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

  27. Total Lesion Frequency and EDSS 5 4 3 2 10 8 6 4 2 Number of Gd enhancing lesions EDSS 12 24 36 48 Months Kindly provided by Joe Frank, NIH

  28. 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

  29. 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

  30. Conclusion Treat the patient, not the test. Dr. T. Traboulsee, UBC MS/MRI Research Group.

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